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After vaccination with enterovirus 71 (EV-A71), the prevalence of hand-foot-and-mouth disease (HFMD) remained high, and the spatial–temporal distribution of enteroviruses changed. Therefore, it is essential to define the temporal features, spatial distributions, and epidemiological and etiological characteristics of HFMD in Kunming. Between 2017 and 2020, a total of 36,540 children were diagnosed with HFMD in Kunming, including 32,754 children with enterovirus-positive clinical samples. Demographic, geographical, epidemiological and etiological data of the cases were acquired and analyzed. Other enteroviruses replaced EV-A71, and the incidence of EV-A71 decreased dramatically, whereas coxsackievirus A6 (CV-A6) and coxsackievirus A16 (CV-A16) had substantial outbreaks in 2018 and 2019, respectively. The major and minor peaks all extended for 2–4 months compared to before vaccination with the EV-A71 vaccine. From 2019 to 2020, CV-A6, as the predominant serotype, showed only a single peak. Although a high incidence of HFMD was observed in Guandu, Chenggong and Xishan, the annual incidence of different enterovirus serotypes was different in different regions. In 2017, other enteroviruses were most prevalent in Shilin. In 2018, CV-A16 and CV-A6 were most prevalent in Luquan and Shilin, respectively. In 2019, CV-A16 was most prevalent in Jinning. In 2020, CV-A6 and coxsackievirus A10 (CV-A10) were most prevalent in Luquan and Shilin, respectively. Meanwhile, the epidemic cycle of CV-A6 and CV-A16 was only 1 year, and CV-A10 and other enteroviruses were potential risk pathogens. The spatial and temporal distribution of HFMD varies at different scales, and the incidence of HFMD associated with different pathogens has obvious regional differences and seasonal trends. Therefore, research on multivalent combined vaccines is urgently needed, and proper preventive and protective measures could effectively control the incidence of HFMD-like diseases.

The absolute dominant species that infests wild population of Przewalski’s horse (Equus przewalskii) is Gasterophilus pecorum, and feces of released Przewalski’s horse, a habitat odor, plays an important role in mating and ovipositing locations of G. pecorum. To screen out unique volatiles for attracting G. pecorum, volatiles from fresh feces of released horses at stages of pre-oviposition (PREO), oviposition (OVIP), and post-oviposition (POSO) of G. pecorum, and feces with three different freshness states (i.e., Fresh, Semi-fresh, and Dry) at OVIP were collected by dynamic headspace adsorption and determined by automatic thermal desorption GC–MS. Results show that there were significant differences in fecal volatiles within both test conditions. Of the five most abundant volatiles from the five individual samples, the most important volatile was ammonium acetate at OVIP/Fresh, followed by acetophenone (Semi-fresh), toluene (PREO, OVIP and POSO), butanoic acid (OVIP and Semi-fresh), acetic acid (PREO, POSO and Semi-fresh), 1,6-octadiene,3,7-dimethyl-,(S)- (PREO, OVIP and POSO), 1,5,9-undecatriene,2,6,10-trimethyl-,(Z)- (PREO and Semi-fresh) and caprolactam (all conditions), which seem to be critical substances in oviposition process of G. pecorum. The findings may be beneficial to development of G. pecorum attractants, facilitating prevention and control of infection by G. pecorum to released Przewalski’s horse.

Vine tea (Ampelopsis grossedentata) has been approved as a new food ingredient in 2013. Both vine tea extract (VTE) and its active ingredient, 2R, 3R-Dihydromyricetin (DMY), showed good antibacterial activity. The mechanism of VTE and DMY against Staphylococcus aureus were evaluated by morphology observation, cell membrane and wall assay, protein assay, and DNA assay in this study. The results of SEM and TEM revealed that the VTE and DMY changed the morphology of S. aureus. The leakage of AKPase and β-galactosidase in treated groups demonstrated that the membrane integrity of S. aureus was disrupted. Meanwhile, the results of protein assay showed that VTE and DMY inhibited the expression of total proteins, and decreased activities of a few energy metabolism enzymes, total ATPase. Moreover, spectral and competitive analysis revealed that VTE and DMY interacted with DNA by groove and intercalation binding. Finally, the suspension experiments of Chinese cabbage and barley showed that inhibitors had strong inhibitory effect on bacteria growth. Overall, the results suggested that VTE and DMY may be potential food preservatives for inhibiting pathogen.

Previous studies have linked the WNT pathway and human skeleton formation; therefore, genes related to WNT might contribute to the onset and development of osteoporosis. In this study, we investigated the potential genetic association of WLS, which encodes an important mediator in the WNT pathway, with osteoporosis and its related quantitative traits in a sample of 6,620 individuals from Han Chinese population. A two-stage approach, with a discovery stage with 859 cases and 1,690 controls and a validation stage with 1,039 cases and 3,032 controls, was applied in the study. Forty SNPs were genotyped in the discovery stage. The intronic SNP rs2566752 was identified to be significantly associated with osteoporosis (ORdiscovery = 0.78, Pdiscovery = 3.73 × 10−5; ORvalidation = 0.80, Pvalidation = 1.96 × 10−5). Two SNPs surrounding rs2566752 (in addition to this SNP itself) were identified to be associated with bone mineral density. In addition, we have identified a 20 kb peak region of H3K27Ac histone mark enrichment between rs2772304 and rs2566752. Our study suggested that WLS is an important locus for osteoporosis and its related quantitative phenotypes in Han Chinese population. Additional sequencing-based studies are needed to investigate the genetic architecture of this regulatory region and its relationship with osteoporosis-related phenotypes.

Autism spectrum disorder (ASD) is not a single disease but a set of disorders. To find clues of ASD pathogenesis in transcriptomic data, we performed an integrated transcriptomic analysis of ASD. After screening based on several standards in Gene Expression Omnibus (GEO) database, we obtained 11 series of transcriptomic data of different human tissues of ASD patients and healthy controls. Multidimensional scaling analysis revealed that datasets from the same tissue had bigger similarity than from different tissues. Functional enrichment analysis demonstrated that differential expressed genes were significantly enriched in inflammation/immune response, mitochondrion-related function and oxidative phosphorylation. Interestingly, genes enriched in inflammation/immune response were up-regulated in the brain tissues and down-regulated in the blood. In addition, drug prediction provided several compounds which might reverse gene expression profiles of ASD patients. And we also replicated the methods and criteria of transcriptomic analysis with datasets of ASD animal models and healthy controls, the results from animal models consolidated the results of transcriptomic analysis of ASD human tissues. In general, the results of our study may provide researchers a new sight of understanding the etiology of ASD and clinicians the possibilities of developing medical therapies.

The reproductive physiology and laying performance of laying hens are regulated by the hypothalamus and pituitary. To understand the mechanism of egg laying regulation, we sequenced and analysed the hypothalamus and pituitary expression profiles in high- and low-yielding laying Chinese Dagu Chickens (CDC) using RNA-seq. More than 46 million clean reads and 24,873 tentative genes were obtained using the Gallus gallus genome as a reference. Transcriptome analysis in hypothalamus and pituitary revealed seven and 39 differentially expressed genes (DEGs) between high- and low-yielding CDC hens, respectively. A total of 24 and 22 DEGs were up-regulated and down-regulated, respectively, and 13 novel genes were identified. Functional annotation and pathway enrichment analysis showed that DEGs in the hypothalamus were mainly enriched in glycosaminoglycan biosynthesis. DEGs significantly enriched in the pituitary primarily affected the extracellular matrix, the protein extracellular matrix, and the extracellular space. Pathways involving phenylalanine metabolism, 2-oxocarboxylic acid metabolism, the glycosphingolipid biosynthesis-ganglion series, and local adhesion were significantly enriched in the pituitary. Eight DEGs, PRDX6, TRIB2, OVCH2, CFD, Peptidase M20, SLC7A10, and two other amino acid transporters, are involved in the metabolism and transport of amino acids. To our knowledge, this is the first study comparing the hypothalamus and pituitary transcriptomes of high- and low-yielding laying hens. Our findings suggest that putative differences in gene expression can provide a base for further research in this field. Moreover, we identified increased expression of genes involved in amino acid metabolism, glycosaminoglycan biosynthesis, and oestrogen negative feedback systems in low-yielding laying hens, highlighting their potential as biomarkers of egg production.

Increasing planting density is the main method and key management to enhance the grain yield. Preventing lodging and premature senescence in high planting density, and screening and enhancing the density-tolerance of maize variety is the main goal of agronomy. Differential response of maize hybrids to high plant density greatly affect the dry matter accumulation and its allocation to maize kernel, depending upon various traits responsible for crowding stress tolerance, of which ear characteristics are pivotal. Density resistance as a quality appraisal of certain variety permits the construction of a simple and accurate method to determine this value, useful for plant breeding. Therefore, we created a new quantitative method, which tested several maize varieties planted populary in China (e.g. Zhengdan 958, Xianyu 335, and Denghai 661) to quantify their response to crowding stress through model. We established 13 planting densities (ranging 1.67–16.67 plants m−2) by adopting fixed line spacing (80 × 40 cm) and then gradually increasing row spacing from 1 m to increasing planting density. A conventional standard plot was also established for verification and evaluation of the plant morphologic characteristics, ear traits, and the yield of maize at various standard densities during 5-year study period. By studying the density–yield relationship, a quantitative model was constructed to identify the density resistance of maize. Grain yield of maize varieties under varying planting densities were simulated, and models of population yield and yield per plant that fitted the data well with high biological significance were produced. From the models, the optimal density of the popular main maize varieties planted in China and the morphological characteristics of each variety at that density were identified. The density-resistance of each variety was referred to as the ear-sensitivity classification. With the highest yield at the optimal density, the plant height of each variety reached 98% to that of tallest plant. The ear/plant ratio was about 0.45, and the ratio between the stem diameter and the largest stem diameter was 0.65–0.80. During the harvest period, the ratio between average single-plant yield and the highest single-plant yield was 0.40–0.50. By gradually increasing planting density, the density resistance of the maize and the changes in yield with density were quantified. Present study provides a convenient tool for the effective selection of varieties by plant breeders through this method and model will help to rapidly identify the density resistance for a new variety and accurate confirmation to optimal planting density, it could be optimized to enable practical production at reasonable planting densities.

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders. Recent studies reported that children with ASD have altered gut microbiota profiles compared with typical development (TD) children. However, few studies on gut bacteria of children with ASD have been conducted in China. Here, in order to elucidate changes of fecal microbiota in children with ASD, 16S rRNA sequencing was conducted and the 16S rRNA (V3-V4) gene tags were amplified. We investigated differences in fecal microbiota between 35 children with ASD and 6 TD children. At the phylum level, the fecal microbiota of ASD group indicated a significant increase of the Bacteroidetes/Firmicutes ratio. At the genus level, we found that the relative abundance of Sutterella, Odoribacter and Butyricimonas was much more abundant in the ASD group whereas the abundance of Veillonella and Streptococcus was decreased significantly compared to the control group. Functional analysis demonstrated that butyrate and lactate producers were less abundant in the ASD group. In addition, we downloaded the association data set of microbe–disease from human microbe–disease association database and constructed a human disease network including ASD using our gut microbiome results. In this microbe–disease network based on microbe similarity of diseases, we found that ASD is positively correlated with periodontal, negatively related to type 1 diabetes. Therefore, these results suggest that microbe-based disease analysis is able to predict novel connection between ASD and other diseases and may play a role in revealing the pathogenesis of ASD.

Lumbar disc herniation (LDH) is a common spine disease characterized by a tear in the disc ring and bulges out at the soft portion. COMT is a protein coding gene located at 22q11.21, and its gene product is a major mammalian enzyme involved in the degradation of catecholamines. A total of 2,678 study subjects with Chinese Han ancestry were recruited and 15 SNPs were selected for genotyping in our study subjects. A synonymous coding SNP, rs4633, was identified to be significantly associated with the disease status of LDH after adjusting for BMI (OR = 0.76, P = 4.83 × 10−5). This SNP was also identified to be significantly associated with COMT gene expression in three types of human tissues. Minor alleles of rs4633 (T) increased the expression of COMT in these 3 tissues. We have identified a significant SNP of COMT, rs4633, which is associated with symptomatic LDH in a large Chinese Han-based sample of the study subjects. This significant finding is further replicated by haplotypic analysis. Evidence from bioinformatics analyses have shown that rs4633 is also significantly associated with the gene expression of COMT. Our findings provide additional supportive evidence for an important role of COMT gene in the symptomatic LDH susceptibility.

Brain hypometabolism is a common epilepsy-related finding in both patients and animal models. Fluorodeoxyglucose positron emission tomography studies have shown that recurrent seizures lead to reduced glucose metabolism in certain brain regions, but no studies have definitively determined whether this induces epileptogenesis. There is evidence that acid-sensing ion channel 2a (ASIC2a) affects epilepsy susceptibility. Transcription factor CP2 (TFCP2) regulates ASIC2a expression. We report that suppressed TFCP2 expression and elevated ASIC2a expression were associated with glucose hypometabolism in the hippocampi of humans with epilepsy and of rat epilepsy model brains. In cultured PC12 cells, we determined that glucose deficiency led to TFCP2 downregulating ASIC2a. Moreover, electrophysiological recordings from cultured rat hippocampal slices showed that ASIC2a overexpression resulted in more action potentials in CA1 pyramidal neurons and increased seizure susceptibility. Our findings suggest that hippocampal glucose hypometabolism elevates ASIC2a expression by suppressing TFCP2 expression, which further enhances the intrinsic excitability of CA1 pyramidal neurons and increases seizure susceptibility in patients with temporal lobe epilepsy.

Increasing studies have demonstrated that sevoflurane can induce neurotoxicity in the developing brains. JNK normally promotes apoptosis. It was hypothesized that sevoflurane affected the proliferation and differentiation of FNSCs and induced cell apoptosis, which caused the learning and memory deficits via JNK pathway. Sevoflurane at a concentration of 1.2% did not induce damage on the FNSCS. However, concentrations of 2.4% and 4.8% decreased the cell viability, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and increased apoptosis, as shown by flow cytometry. The 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay demonstrated that 4.8% sevoflurane reduced the proliferation of FNSCs. Compared with the control group, the 4.8% sevoflurane group showed a decrease in the proportion of undifferentiated FNSCs at 6-h exposure; 4.8% sevoflurane could increase the p-JNK/JNK ratio. JNK inhibition by the specific inhibitor SP600125 enhanced partially the cell viability. Cumulatively, 4.8% sevoflurane induced significant damage on FNSCs; it decreased cell proliferation and proportion of undifferentiated cells as well. JNK pathway might play a key role in the decrease in survival of FNSCs induced by an inhaled anesthetic. The present findings might raise the possibility that JNK inhibition has therapeutic potential in protecting FNSCs from the adverse effects of the inhaled anesthetic.

Choroidal neovascularization(CNV) is the most severe complication in Age-related macular degeneration(AMD) and the most common cause of irreversible blindness in the elderly in developed world. The aim of this study was to identify the effect of transforming growth factor-β(TGF-β) and Smad2/3-VEGF/TNF-α signaling on CNV angiopoiesis, and to explore TGF-β inhibitors on the development of CNV in a CNV mouse model. Fundus fluorescein angiography(FFA) was used to evaluate the laser-induced CNV formation. The histology of CNV lesions stained with hematoxylin-eosin(HE) was obtained. The immunofluorescent staining was performed to determine TGF-β protein expression. The expressions of TGF-β, phosphorylated Smad2/3, VEGF and TNF-α were determined by using Western blot analysis. The CNV areas were analyzed by using fluorescein stain on RPE/choroid-sclera flat mounts. We found the levels of TGF-β protein expression increasingly reached the peak till 3rd week during the CNV development. The protein levels of VEGF and TNF-α also increased significantly in CNV mice, which were inhibited by a synthetic TGF-β inhibitor LY2157299 or a natural TGF-β inhibitor Decorin. The phosphorylated Smad2/3 levels increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-β inhibitors. Here we have demonstrated that TGF-β/Smad signaling plays an important role in Laser-induced CNV formation through down-regulation of VEGF and TNF-α expressions, suggesting TGF-β inhibitors may provide an alternative to traditional methods in wet AMD treatment.

The microbiota colonized on human body is renowned as “a forgotten organ” due to its big impacts on human health and disease. Recently, microbiome studies have identified a large number of microbes differentially regulated in a variety of conditions, such as disease and diet. However, methods for discovering biological patterns in the differentially regulated microbes are still limited. For this purpose, here, we developed a web-based tool named MicroPattern to discover biological patterns for a list of microbes. In addition, MicroPattern implemented and integrated an algorithm we previously presented for the calculation of disease similarity based on disease-microbe association data. MicroPattern first grouped microbes into different sets based on the associated diseases and the colonized positions. Then, for a given list of microbes, MicroPattern performed enrichment analysis of the given microbes on all of the microbe sets. Moreover, using MicroPattern, we can also calculate disease similarity based on the shared microbe associations. Finally, we confirmed the accuracy and usefulness of MicroPattern by applying it to the changed microbes under the animal-based diet condition. MicroPattern is freely available at http://www.cuilab.cn/micropattern.

Both brown adipocytes (BAC) and beige cells hold therapeutic potential for the treatment of metabolic disorders. Unfortunately, the amount and activity of these cells are limited in adults. Although BAC marker expression has been shown in peri-renal adipose tissues in children and adults, functional assessment is lacking. Furthermore, it is entirely unknown whether adipose progenitors are present in human embryo and able to give rise to BAC in situ during evolution. Therefore, adipose tissues in the interscapular and peri-renal regions were dissected from human embryo and subcutaneous white adipose tissues (sWAT) were obtained from an adult. After subjected to differentiation in vitro, adipocyte progenitors were detected present in all these adipose tissues. When stimulated for adipogenesis, differentiated adipocytes in the intercapular and peri-renal regions showed similar features: (1) induced BAC and beige cell marker expression including UCP1 and PRDM16 and comparable mitochondrion copy number; (2) similar gene expression patterns by RNA-Seq analysis; and (3) similar maximal oxygen consumption rates examined by respirometry. Nevertheless, stimulation of adipocyte progenitors in sWAT induces neither BAC and beige cell marker expression nor any change of oxygen consumption. In conclusion, peri-renal adipocyte progenitors in human embryo hold browning potential for BAC production.

By using immunostaining and three-dimensional reconstruction, the anatomical organization of the antennal lobe glomeruli of the female cotton bollworm Helicoverpa armigera was investigated. Eighty-one glomeruli were identified, 15 of which were not previously discovered. The general anatomical organization of the AL of female is similar to that of male and all glomeruli were classified into four sub-groups, including the female-specific glomerular complex, posterior complex, labial-palp pit organ glomerulus, and ordinary glomeruli. A global-wide comparison on the complete glomerular map of female and male was performed and for the first time the quantitative difference in volume for each individual homologous glomerulus was analyzed. We found that the sexual dimorphism includes not only the sex-specific glomeruli but also some of the other glomeruli. The findings in the present study may provide a reference to examine the antennal-lobe organization more in detail and to identify new glomeruli in other moth species. In addition, the complete identification and global-wide comparison of the sexes provide an important basis for mapping the function of distinct glomeruli and for understanding neural mechanisms underlying sexually dimorphic olfactory behaviors. © The Author(s) 2016. Published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

The Qianhua Mutton Merino (QHMM) is a new sheep (Ovis aries) variety with better meat performance compared with the traditional local variety Small Tail Han (STH) sheep. We aimed to evaluate the transcriptome regulators associated with muscle growth and development between the QHMM and STH. We used RNA-Seq to obtain the transcriptome profiles of the longissimus muscle from the QHMM and STH. The results showed that 960 genes were differentially expressed (405 were up-regulated and 555 were down-regulated). Among these, 463 differently expressed genes (DEGs) were probably associated with muscle growth and development and were involved in biological processes such as skeletal muscle tissue development and muscle cell differentiation; molecular functions such as catalytic activity and oxidoreductase activity; cellular components such as mitochondrion and sarcoplasmic reticulum; and pathways such as metabolic pathways and citrate cycle. From the potential genes, a gene-act-network and co-expression-network closely related to muscle growth and development were identified and established. Finally, the expressions of nine genes were validated by real-time PCR. The results suggested that some DEGs, including MRFs, GXP1 and STAC3, play crucial roles in muscle growth and development processes. This genome-wide transcriptome analysis of QHMM and STH muscle is reported for the first time.

In higher plants, Heat Shock Protein 20 (Hsp20) plays crucial roles in growth, development and responses to abiotic stresses. In this study, 94 GhHsp20 genes were identified in G. hirsutum, and these genes were phylogenetically clustered into 14 subfamilies. Out of these, 73 paralogous gene pairs remained in conserved positions on segmental duplicated blocks and only 14 genes clustered into seven tandem duplication event regions. Transcriptome analysis showed that 82 GhHsp20 genes were expressed in at least one tested tissues, indicating that the GhHsp20 genes were involved in physiological and developmental processes of cotton. Further, expression profiles under abiotic stress exhibited that two-thirds of the GhHsp20 genes were responsive to heat stress, while 15 genes were induced by multiple stresses. In addition, qRT-PCR confirmed that 16 GhHsp20 genes were hot-induced, and eight genes were up-regulated under multiple abiotic stresses and stress-related phytohormone treatments. Taken together, our results presented here would be helpful in laying the foundation for understanding the complex mechanisms of GhHsp20 mediated developmental processes and abiotic stress signaling transduction pathways in cotton.

MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells’ sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC.

An aberrant artery (AA) can frequently be observed coursing through the fissure for the ligamentum venosum (FLV) which was termed the “vessel through strait” sign (VTSS) by us. Fundamental data including the incidence, anatomical composition and clinical significance of VTSS and the AAs composing VTSS are still lacking. We sought to give a systematic demonstration on this issue in the present study. VTSS was respectively analyzed in 2,275 patients and was observed in 357 of them. Interestingly, 319 (89.4%) out of the 357 patients exhibiting VTSS were proved to have left hepatic artery variation (LHAV) (247 with replaced left hepatic artery, 64 with accessory left hepatic artery and 8 with variant common hepatic artery). We therefore hypothesized that VTSS could be a sign that strongly associated with LHAV and could be used for its diagnosis. In the following validating analysis, VTSS gained a sensitivity of 96.3% and a specificity of 98.3% for the diagnosis of LHAV in another bicenter cohort consisted of 1,329 patients. In conclusion, VTSS is a signature radiological sign of LHAV which could be used as an easy and specific method for the diagnosis of LHAV.

Congenital heart defects (CHDs) are the most common group of major birth defects. Presently there are no clinically used biomarkers for prenatally detecting CHDs. Here, we performed a comprehensive maternal serum proteomics assessment, combined with immunoassays, for the discovery of non-invasive biomarkers for prenatal diagnosis of CHDs. A total of 370 women were included in this study. An isobaric tagging for relative and absolute quantification (iTRAQ) proteomic approach was used first to compare protein profiles in pooled serum collected from women who had CHD-possessing or normal fetuses and 47 proteins displayed significant differential expressions. Targeted verifications were performed on 11 proteins using multiple reaction monitoring mass spectrometry (MRM-MS) and the resultant candidate biomarkers were then further validated using ELISA analysis. Finally, we identified a biomarker panel composed of 4 cytoskeletal proteins capable of differentiating CHD-pregnancies from normal ones [with an area under the receiver operating characteristic curve (AUC) of 0.938, P

To identify candidate serum molecule biomarkers for the non-invasive early prenatal diagnosis of neural tube defects (NTDs), we employed an iTRAQ-based quantitative proteomic approach to analyze the proteomic changes in serum samples from embryonic day (E) 11 and E13 pregnant rats with spina bifida aperta (SBA) induced by all-trans retinoic acid. Among the 390 proteins identified, 40 proteins at E11 and 26 proteins at E13 displayed significant differential expression in the SBA groups. We confirmed 5 candidate proteins by ELISA. We observed the space-time expression changes of proprotein convertase subtilisin/kexin type 9 (PCSK9) at different stages of fetal development, including a marked decrease in the sera of NTD pregnancies and gradual increase in the sera of normal pregnancies with embryonic development. PCSK9 demonstrated the diagnostic efficacy of potential NTD biomarkers [with an area under the receiver operating characteristic curve of 0.763, 95% CI: 065–0.88]. Additionally, PCSK9 expression in the spinal cords and placentas of SBA rat fetuses was markedly decreased. PCSK9 could serve as a novel molecular biomarker for the non-invasive prenatal screening of NTDs and may be involved in the pathogenesis of NTDs at critical periods of fetal development.

Intramolecular electronic communications of molecular wires play a crucial role for developing molecular devices. In the present work, we describe different degrees of intramolecular electronic communications in the redox processes of three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by electrochemistry and Density Functional Theory (DFT) methods in different solvents. We found that the bridges linkers have a significant effect on the electronic communications between the two peripheral ubiquinone moieties and solvents effects are limited and mostly depend on the nature of solvents. The DFT calculations for the first time indicate the intensity of the electronic communications during the redox processes rely on the molecular orbital elements VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1), which is could be affected by the bridges linkers. The DFT calculations also demonstrates the effect of solvents on the latter two-electron transfer of Bis-CoQ0s is more significant than the former two electrons transfer as the observed electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry and theoretical calculations reveal the intramolecular electronic communications vary in the four-electron redox processes of three Bis-CoQ0s.

Diketopiperazines are important secondary metabolites of the fungi with variety bioactivities. Several species belonging to genus Chaetomium produce compounds of this class, such as chetomin. To identify new antitumor agents, secondary metabolites of fungus Chaetomium sp 88194 were investigated and three new indole diketopiperazines, Chaetocochins G (1), Oidioperazines E (2) and Chetoseminudin E (3), along with two known compounds Chetoseminudins C (4) and N-acetyl-β-oxotryptamine (5), were obtained. Chaetocochins G and Chetoseminudin E were recrystallized in CHCl3 containing a small amount of MeOH and their structures with absolute configuration were established by spectroscopic data interpretation and single-crystal X-ray diffraction analysis. The absolute configuration of Oidioperazines E was defined by comparing of experimental and calculated electronic circular dichroism spectra. These isolates were also evaluated the anticancer activity and Chaetocochins G displayed more potent cytotoxicity in MCF-7 cells than the common chemotherapeutic agent (5-fluorouracil) associated with G2/M cell cycle arrest. More importantly, Chaetocochins G induced cell apoptotic death via caspase-3 induction and proteolytic cleavage of poly (ADP-ribose) polymerase, concomitantly with increased Bax and decreased Bcl-2 expression. Our findings suggested that indole diketopiperazines from endophytic Chaetomium sp 88194 may be potential resource for developing anti-cancer reagents.

There is an increasing demand for identifying the functional sites of noncoding RNAs (ncRNAs). Here we introduce a tertiary-structure based computational approach, Rsite, which first calculates the Euclidean distances between each nucleotide and all the other nucleotides in a RNA molecule and then determines the nucleotides that are the extreme points in the distance curve as the functional sites. By analyzing two ncRNAs, tRNA (Lys) and Diels-Alder ribozyme, we demonstrated the efficiency of Rsite. As a result, Rsite recognized all of the known functional sites of the two ncRNAs, suggesting that Rsite could be a potentially useful tool for discovering the functional sites of ncRNAs. The source codes and data sets of Rsite are available at http://www.cuilab.cn/rsite.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus.

Chiral nanoscale photonic systems typically follow either tetrahedral or helical geometries that require four or more different constituent nanoparticles. Smaller number of particles and different chiral geometries taking advantage of the self-organization capabilities of nanomaterials will advance understanding of chiral plasmonic effects, facilitate development of their theory, and stimulate practical applications of chiroplasmonics. Here we show that gold nanorods self-assemble into side-by-side orientated pairs and "ladders" in which chiral properties originate from the small dihedral angle between them. Spontaneous twisting of one nanorod versus the other one breaks the centrosymmetric nature of the parallel assemblies. Two possible enantiomeric conformations with positive and negative dihedral angles were obtained with different assembly triggers. The chiral nature of the angled nanorod pairs was confirmed by 4π full space simulations and the first example of single-particle CD spectroscopy. Self-assembled nanorod pairs and "ladders" enable the development of chiral metamaterials, (bio)sensors, and new catalytic processes.

CORRIGENDUM: Ubiquinone-quantum dot bioconjugates for in vitro and intracellular complex I sensing

Quantum dots (QDs) have attracted increasing interest in bioimaging and sensing. Here, we report a biosensor of complex I using ubiquinone-terminated disulphides with different alkyl spacers (QnNS, n = 2, 5 and 10) as surface-capping ligands to functionalise CdSe/ZnS QDs. The enhancement or quenching of the QD bioconjugates fluorescence changes as a function of the redox state of QnNS, since QDs are highly sensitive to the electron-transfer processes. The bioconjugated QnNS-QDs emission could be modulated by complex I in the presence of NADH, which simulates an electron-transfer system part of the mitochondrial respiratory chain, providing an in vitro and intracellular complex I sensor. Epidemiological studies suggest that Parkinson's patients have the impaired activity of complex I in the electron-transfer chain of mitochondria. We have demonstrated that the QnNS-QDs system could aid in early stage Parkinson's disease diagnosis and progression monitoring by following different complex I levels in SH-SY5Y cells.