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Ying Wang - Top 30 Publications

Genetic and Cytological Analyses of the Natural Variation of Seed Number per Pod in Rapeseed (Brassica napus L.).

Seed number is one of the key traits related to plant evolution/domestication and crop improvement/breeding. In rapeseed germplasm, the seed number per pod (SNPP) shows a very wide variation from several to nearly 30; however, the underlying causations/mechanisms for this variation are poorly known. In the current study, the genetic and cytological bases for the natural variation of SNPP in rapeseed was firstly and systematically investigated using the representative four high-SNPP and five low-SNPP lines. The results of self- or cross-pollination experiment between the high- and low-SNPP lines showed that the natural variation of SNPP was mainly controlled by maternal effect (mean = 0.79), followed by paternal effect (mean = 0.21). Analysis of the data using diploid seed embryo-cytoplasmic-maternal model further showed that the maternal genotype, embryo, and cytoplasm effects, respectively, explained 47.6, 35.2, and 7.5% of the genetic variance. In addition, the analysis of combining ability showed that for the SNPP of hybrid F1 was mainly determined by the general combining ability of parents (63.0%), followed by special combining ability of parental combination (37.0%). More importantly, the cytological observation showed that the SNPP difference between the high- and low-SNPP lines was attributable to the accumulative differences in its components. Of which, the number of ovules, the proportion of fertile ovules, the proportion of fertile ovules to be fertilized, and the proportion of fertilized ovules to develop into seeds accounted for 30.7, 18.2, 7.1, and 43.9%, respectively. The accordant results of both genetic and cytological analyses provide solid evidences and systematic insights to further understand the mechanisms underlying the natural variation of SNPP, which will facilitate the development of high-yield cultivars in rapeseed.

Progressive Colonization of Bacteria and Degradation of Rice Straw in the Rumen by Illumina Sequencing.

The aim of this study was to improve the utilization of rice straw as forage in ruminants by investigating the degradation pattern of rice straw in the dairy cow rumen. Ground up rice straw was incubated in situ in the rumens of three Holstein cows over a period of 72 h. The rumen fluid at 0 h and the rice straw at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 h were collected for analysis of the bacterial community and the degradation of the rice straw. The bacterial community and the carbohydrate-active enzymes in the rumen fluid were analyzed by metagenomics. The diversity of bacteria loosely and tightly attached to the rice straw was investigated by scanning electron microscopy and Miseq sequencing of 16S rRNA genes. The predominant genus in the rumen fluid was Prevotella, followed by Bacteroides, Butyrivibrio, unclassified Desulfobulbaceae, Desulfovibrio, and unclassified Sphingobacteriaceae. The main enzymes were members of the glycosyl hydrolase family, divided into four categories (cellulases, hemicellulases, debranching enzymes, and oligosaccharide-degrading enzymes), with oligosaccharide-degrading enzymes being the most abundant. No significant degradation of rice straw was observed between 0.5 and 6 h, whereas the rice straw was rapidly degraded between 6 and 24 h. The degradation then gradually slowed between 24 and 72 h. A high proportion of unclassified bacteria were attached to the rice straw and that Prevotella, Ruminococcus, and Butyrivibrio were the predominant classified genera in the loosely and tightly attached fractions. The composition of the loosely attached bacterial community remained consistent throughout the incubation, whereas a significant shift in composition was observed in the tightly attached bacterial community after 6 h of incubation. This shift resulted in a significant reduction in numbers of Bacteroidetes and a significant increase in numbers of Firmicutes. In conclusion, the degradation pattern of rice straw in the dairy cow rumen indicates a strong contribution by tightly attached bacteria, especially after 6 h incubation, but most of these bacteria were not taxonomically characterized. Thus, these bacteria should be further identified and subjected to functional analysis to improve the utilization of crop residues in ruminants.

Three-Dimensional Superresolution Imaging of the FtsZ Ring during Cell Division of the Cyanobacterium Prochlorococcus.

Superresolution imaging has revealed subcellular structures and protein interactions in many organisms. However, superresolution microscopy with lateral resolution better than 100 nm has not been achieved in photosynthetic cells due to the interference of a high-autofluorescence background. Here, we developed a photobleaching method to effectively reduce the autofluorescence of cyanobacterial and plant cells. We achieved lateral resolution of ~10 nm with stochastic optical reconstruction microscopy (STORM) in the sphere-shaped cyanobacterium Prochlorococcus and the flowering plant Arabidopsis thaliana During the cell cycle of Prochlorococcus, we characterized the three-dimensional (3D) organization of the cell division protein FtsZ, which forms a ring structure at the division site and is important for cytokinesis of bacteria and chloroplasts. Although the FtsZ ring assembly process in rod-shaped bacteria has been studied extensively, it has rarely been studied in sphere-shaped bacteria. Similarly to rod-shaped bacteria, our results with Prochlorococcus also showed the assembly of FtsZ clusters into incomplete rings and then complete rings during cell division. Differently from rod-shaped bacteria, the FtsZ ring diameter was not found to decrease during Prochlorococcus cell division. We also discovered a novel double-Z-ring structure, which may be the Z rings of two daughter cells in a predivisional mother cell. Our results showed a quantitative picture of the in vivo Z ring organization of sphere-shaped bacteria.IMPORTANCE Superresolution microscopy has not been widely used to study photosynthetic cells due to their high-autofluorescence background. Here, we developed a photobleaching method to reduce the autofluorescence of cyanobacteria and plant cells. After photobleaching, we performed superresolution imaging in the cyanobacterium Prochlorococcus and the flowering plant Arabidopsis thaliana with ~10-nm resolution, which is the highest resolution in a photosynthetic cell. With this method, we characterized the 3D organization of the cell division protein FtsZ in Prochlorococcus We found that the morphological variation of the FtsZ ring during cell division of the sphere-shaped cyanobacterium Prochlorococcus is similar but not identical to that of rod-shaped bacteria. Our method might also be applicable to other photosynthetic organisms.

Chemical Cosubstitution-Oriented Design of Rare-Earth Borates as Potential Ultraviolet Nonlinear Optical Materials.

Chemical cosubstitution strategy was implemented to design the potential ultraviolet (UV) and deep-UV nonlinear optical (NLO) materials. Taking the classic β-BaB2O4 as a maternal structure, by simultaneously replacing the Ba2+ and [B3O6]3- units for monovalant (K+), divalent (alkaline earth metal), trivalent (rare-earth metal, Bi3+) ions, and the [B5O10]5- clusters through two different practical routes, altogether twelve new mixed-metal noncentrosymmetric borates K7MIIRE2(B5O10)3 (MII = Ca, Sr, Ba, K/RE0.5; RE = Y, Lu, Gd) as well as K7MIIBi2(B5O10)3 (MII = Pb, Sr) were successfully designed and synthesized as high-quality single crystals. The selected K7CaY2(B5O10)3, K7SrY2(B5O10)3, and K7BaY2(B5O10)3 compounds were performed all-round characterizations via experimental and theoretical ways. They all exhibit suitable second-harmonic generation (SHG) responses as large as the commercial KH2PO4 (KDP) and short UV cutoff edges. These results confirm the feasibility of chemical cosubstitution strategy to design NLO materials and the three seclected crystals may have potential application as UV NLO materials.

Feasibility of high-concentration cellulosic bioethanol production from undetoxified whole Monterey pine slurry.

The economic feasibility of high-concentration cellulosic bioethanol production remains challenging because it requires easily available feedstock and low energy consumption process. Simultaneous saccharification and fermentation (SSF) of sulfite pretreated Momentary pine slurry at 20% (w/w) loadings increased ethanol concentration from 59.3 g/L to 68.5 g/L by washing strategy. Effects of inhibitors in pretreatment liquor were further investigated. Besides HMF, furfural and acetic acid, other inhibitors and/or their synergistic effects proved to be responsible for a lower fermentability. To bypass the inhibition and achieve high-efficient bioethanol concentration, a fermentation temperature of 28 °C was optimized for both cell growth and ethanol production. Under the optimal conditions with prehydrolyzed 25% (w/w) whole undetoxified slurry, a high ethanol concentration (up to 82.1 g/L) were produced with a yield of 205 kg/ton Monterey pine in the SSF. Thus, this high cellulosic bioethanol production from Monterey pine makes it a potential strategy for biofuel production.

The usefulness of chief complaints to predict severity, ventilator dependence, treatment option, and short-term outcome of patients with Guillain-Barré syndrome: a retrospective study.

It remains an urgent need for early recognition of disease severity, treatment option and outcome of Guillain-Barré syndrome (GBS). The chief complaint may be quickly obtained in clinic and is one of the candidates for early predictors. However, studies on the chief complaint are still lacking in GBS. The aim of the study is to describe the components of chief complaints of GBS patients, and to explore association between chief complaints and disease severity/treatment option/outcome of GBS, so as to aid the early prediction of the disease course and to assist the clinicians to prescribe an optimal early treatment.

Cytotoxic ring A-seco triterpenoids from the stem bark of Dysoxylum lukii.

A chemical investigation of the 70% ethanol extract from the stem bark of Dysoxylum lukii afforded three new ring A-seco triterpenoids, dysoxylukiines A-C (1-3). Their structures were elucidated on the basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) analyses. The isolated compounds were evaluated in vitro for cytotoxic properties. Consequently, compound 3 exhibited modest cytotoxic activities against four osteosarcoma cell lines (SOSP-9607, MG-63, Saos-2, and M663) with IC50 values less than 10 μM.

Association between electrocardiographic and echocardiographic markers of stage B heart failure and cardiovascular outcome.

The detection of non-ischaemic (mainly hypertension, diabetes, and obesity) stage B heart failure (SBHF) may facilitate the recognition of those at risk of progression to overt HF and HF prevention. We sought the relationship of specific electrocardiographic (ECG) markers of SBHF to echocardiographic features of SBHF and their prognostic value for development of HF. The ECG markers were Cornell product (Cornell-P), P-wave terminal force in lead V1 (PTFV1), ST depression in lead V5 V6 (minSTmV5V6), and increased heart rate. Echocardiographic assessment of SBHF included left ventricular hypertrophy (LVH), impaired global longitudinal strain (GLS), and diastolic dysfunction (DD).

Association of IMMP2L deletions with autism spectrum disorder: A trio family study and meta-analysis.

IMMP2L, the gene encoding the inner mitochondrial membrane peptidase subunit 2-like protein, has been reported as a candidate gene for Tourette syndrome, autism spectrum disorder (ASD) and additional neurodevelopmental disorders. Here we genotyped 100 trio families with an index proband with autism spectrum disorder in Han Chinese population and found three cases with rare exonic IMMP2L deletions. We have conducted a comprehensive meta-analysis to quantify the association of IMMP2L deletions with ASD using 5,568 cases and 10,279 controls. While the IMMP2L deletions carried non-recurrent breakpoints, in contrast to previous reports, our meta-analysis found no evidence of association (P > 0.05) between IMMP2L deletions and ASD. We also observed common exonic deletions impacting IMMP2L in a separate control (5,971 samples) cohort where subjects were screened for psychiatric conditions. This is the first systematic review and meta-analysis regarding the effect of IMMP2L deletions on ASD, but further investigations in different populations, especially Chinese population may be still needed to confirm our results.

PKG II effectively reversed EGF-induced protein expression alterations in human gastric cancer cell lines.

Epidermal growth factor receptor (EGFR) plays an important role in gastric cancer (GC) progression. Our previous data demonstrated that type II cGMP-dependent protein kinase (PKG II) could block the EGF-EGFR axis as well as down-stream signaling pathways for example, MAPK, PI3K and PLC in gastric cancer cells. However, the exact mechanisms of PKG II against cancer remain unclear. Therefore, the present work was to address the above question. Human gastric cancer cell line AGS was infected with adenoviral construct encoding cDNA of PKG II (Ad-PKG II) to up-regulate PKG II and then treated with 8-pCPT-cGMP. Two-dimensional electrophoresis (2-DE) was used to analyze the changes of protein expression in the cells. The results showed that 17 proteins had more than 2-fold changes in EGF-treated group compared with control. However, Ad-PKG II could effectively reversed the changes. Furthermore, far upstream element-binding protein 1 (FUBP1) and MarvelD3 were chosen and PKG II activation reversed EGF/EGFR-induced up-regulation of FUBP1 and downregulation of MarvelD3, respectively. MarvelD3 silence effectively abolished the inhibitory effect of PKG II on EGF-triggered migration. These data indicated that the inhibitory effect of PKG II partially was associated with MarvelD3.

A genetic system for targeted mutations to disrupt and restore genes in the obligate bacterium, Ehrlichia chaffeensis.

Obligate intracellular bacteria (obligates) belonging to Rickettsiales and Chlamydiales cause diseases in hundreds of millions of people worldwide and in many animal species. Lack of an efficient system for targeted mutagenesis in obligates remains a major impediment in understanding microbial pathogenesis. Challenges in creating targeted mutations may be attributed to essential nature of majority of the genes and intracellular replication dependence. Despite success in generating random mutations, a method that works well in creating mutations in specific genes of interest followed by complementation remains problematic for obligates and is a highly sought-after goal. We describe protocols to generate stable targeted mutations by allelic exchange in Ehrlichia chaffeensis, an obligate intracellular tick-borne bacterium responsible for human monocytic ehrlichiosis. Targeted mutations in E. chaffeensis were created to disrupt two genes, and also to restore one gene by another allelic exchange mutation leading to the restoration of transcription and protein expression from the inactivated gene and the recovered organisms also express mCherry, which distinguishes from the wild type. We expect that the methods developed are broadly applicable to other obligates, particularly to rickettsial pathogens, to routinely perform targeted mutations to enable studies focused on protein structure-function analyses, host-pathogen interactions and in developing vaccines.

Rapid and Efficient CRISPR/Cas9-Based Mating-Type Switching of Saccharomyces cerevisiae.

Rapid and highly efficient mating-type switching of Saccharomyces cerevisiae enables a wide variety of genetic manipulations such as the construction of strains, for instance isogenic haploid pairs of both mating-types, diploids and polyploids. We used the CRISPR/Cas9 system to generate a double-strand break (DSB) at the MAT locus, and in a single co-transformation, both haploid and diploid cells were switched to the specified mating-type at ~80% efficiency. The mating-type of strains carrying either rod or ring chromosome III were switched, including those lacking HMLα and HMRa cryptic mating loci.  Furthermore, we transplanted the synthetic yeast chromosome V to build a haploid poly-synthetic chromosome strain by using this method together with an endoreduplication intercross strategy. The CRISPR/Cas9 mating-type switching method will be useful in building the complete synthetic yeast (Sc2.0) genome. Importantly, it is a generally useful method to build polyploids of a defined genotype and generally expedites strain construction, for example in the construction of fully a/a/a/a isogenic tetraploids.

Biospecimen donation among black and white breast cancer survivors: opportunities to promote precision medicine.

Advances in precision medicine (PM) have potential to reduce and/or eliminate breast cancer disparities in both treatment and survivorship. However, compared to white Americans, black Americans are often underrepresented in genetic research. This report assessed factors that influence receipt of buccal cells via saliva kits.

Purification and Identification of a Natural Antioxidant Protein from Fertilized Eggs.

Fertilized hen eggs are rich in a variety of bioactive ingredients. In this study, we aimed to obtain an antioxidant protein from fertilized eggs and the radical scavenging abilities on 1, 1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (•OH), superoxide anion (O(2-)•) were used to evaluate the antioxidant activity of the purified protein. During 20 d of incubation, the radical scavenging ability of protein extracted from fertilized eggs exhibited significantly differences and the protein on day 16 showed higher antioxidant capacity. Based on this, the antioxidant protein of the samples on day 16 were isolated for the follow-up study. With a molecular weight 43.22 kDa, the antioxidant protein was purified by Diethylaminoethyl cellulose -52 (DEAE-52) column and Sephadex G-100. The LC-MS analysis showed that the purified protein molecular weight was 43.22 kDa, named D2-S. The sequence of amino acids was highly similar to ovalbumin and the coverage reached to 84%. The purified protein showed a radical scavenging rate of 52.34±3.27% on DPPH and 63.49±0.25% on •OH, respectively. Furthermore, the C-terminal amino acid sequence was NAVLFFGRCVSP, which was consistent with the sequence of ovabumin. These results here indicated that purified protein may be a potential resource as a natural antioxidant.

Antimicrobial blue light inactivation of pathogenic microbes: State of the art.

As an innovative non-antibiotic approach, antimicrobial blue light in the spectrum of 400-470nm has demonstrated its intrinsic antimicrobial properties resulting from the presence of endogenous photosensitizing chromophores in pathogenic microbes and, subsequently, its promise as a counteracter of antibiotic resistance. Since we published our last review of antimicrobial blue light in 2012, there have been a substantial number of new studies reported in this area. Here we provide an updated overview of the findings from the new studies over the past 5 years, including the efficacy of antimicrobial blue light inactivation of different microbes, its mechanism of action, synergism of antimicrobial blue light with other angents, its effect on host cells and tissues, the potential development of resistance to antimicrobial blue light by microbes, and a novel interstitial delivery approach of antimicrobial blue light. The potential new applications of antimicrobial blue light are also discussed.

Effectiveness of Pharmacist-led Anticoagulation Management on Clinical Outcomes: A Systematic Review and Meta-Analysis.

We performed this systematic review and meta-analysis to confirm whether patients benefit more from pharmacist-led anticoagulation management than other models.

Bone mesenchymal stem cell secretion of sRANKL/OPG/M-CSF in response to macrophage-mediated inflammatory response influences osteogenesis on nanostructured Ti surfaces.

Although it has been well established that osteogenic differentiation of bone mesenchymal stem cells (bMSCs) as well as osteoclastic differentiation of macrophages can be manipulated by the nanostructure of biomaterial surfaces, the interactions among the effects of the surface on immune cells and bMSCs remained unknown. Therefore, in this study, the osteogenic behaviors and secretion of osteoclastogenesis-related cytokines of human bMSCs on TiO2 nanotubular (NT) surfaces in conditioned medium (CM) generated by macrophages cultured on the respective NT surfaces (NT-CM) were analyzed. Although bMSCs showed consistent osteogenic behaviors on the NT5 and NT20 surfaces in both standard culture medium and both types of NT-CM, collagen synthesis and extracellular matrix mineralization were partially impeded on the NT20 surface in NT20-CM and bMSC cytokine secretions on the NT20 surface in NT20-CM elicited remarkable multinuclear giant cell and osteoclast formation compared with that observed on the NT5 surface in NT5-CM. After implantation in vivo, mineralized bone formation was significantly delayed around the NT20 implant compared with the NT5 implant, but both surfaces contributed to good bone formation after 12 weeks. The results obtained in this study advance our understanding of the confounding influence of the implant surface nanostructure, macrophage inflammatory response, and osteogenic differentiation of bMSCs as well as the retro-regulative effects of bMSCs on the osteoclastic differentiation of macrophages, and the culture system based on different NT surfaces and CM generated on the respective surfaces may provide a systematic research model for evaluating the performance of endosseous implants as well as a prospective approach for improving implant osseointegration via immune-regulation.

Silencing of COL1A2, COL6A3 and THBS2 Inhibits Gastric Cancer Cell Proliferation, Migration and Invasion while Promoting Apoptosis through the PI3k-Akt Signaling Pathway.

This study explores the effect of COL1A2, COL6A3, and THBS2 gene silencing on proliferation, migration, invasion, and apoptosis of gastric cancer cells through the PI3K-Akt signaling pathway. The gastric cancer microarray expression data (GSE19826, GSE79973, and GSE65801) was analyzed. Gastric cancer tissues and corresponding adjacent normal tissues were extracted from patients. Positive expression rate of PI3K, Akt, and p-Akt was measured with immunohistochemistry. Two cell lines, BGC-823 and SGC-7901, were transfected and cells were grouped into blank, negative control, COL1A2-shRNA, COL6A3-shRNA, and THBS2-shRNA groups. Expressions of COL1A2, COL6A3, and THBS2 in gastric cancer cells transfected with corresponding silencing sequences were evaluated by RT-qPCR and Western blot. MTT assay, Transwell, and cell scratch tests were conducted to evaluate cell proliferation, invasion, and migration capacity, respectively. Flow cytometry was used to evaluate cell cycle distribution and apoptosis. The positive expression of PI3K, Akt, and p-Akt was higher in gastric cancer tissues compared with adjacent normal tissues, and the mRNA expression of COL1A2, COL6A3, and THBS2 was increased in gastric cancer tissues. Akt, p-Akt, and PI3K expression drastically decreased in cells transfected with COL1A2, COL6A3, and THBS2 silencing sequences. Cells transfected with COL1A2, COL6A3, and THBS2 silencing sequences exhibited promoted apoptosis but inhibited proliferation, migration, and invasion. This study demonstrates that COL1A2, COL6A3, and THBS2 gene silencing inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3K-Akt signaling pathway. This article is protected by copyright. All rights reserved.

A Real-World Comparison of FOLFIRINOX, Gemcitabine Plus nab-Paclitaxel, and Gemcitabine in Advanced Pancreatic Cancers.

FOLFIRINOX (FFN), nab-paclitaxel plus gemcitabine (GN), and gemcitabine are three systemic therapies that provide clinically meaningful benefit to patients with unresectable pancreatic cancer (UPC). There are no clinical trials that directly compare the efficacy of all three regimens. In this study, we aim to examine and compare the real-world effectiveness of these treatments.

Enantioselective Biosynthesis of l-Phenyllactic Acid by Whole Cells of Recombinant Escherichia coli.

l-Phenyllactic acid (l-PLA)-a valuable building block in the pharmaceutical and chemical industry-has recently emerged as an important monomer in the composition of the novel degradable biocompatible material of polyphenyllactic acid. However, both normally chemically synthesized and naturally occurring phenyllactic acid are racemic, and the product yields of reported l-PLA synthesis processes remain unsatisfactory.

Genetic mutational testing of Chinese children with familial hematuria with biopsy‑proven FSGS.

Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH). Previous studies revealed that long‑time persistent microscopic hematuria may lead to FSGS. A case of a family is presented here where affected individuals exhibited FH with FSGS‑proven, or chronic kidney disease. Renal biopsies were unhelpful and failed to demonstrate glomerular or basement membrane defects consistent with an inherited glomerulopathy, and therefore a possible underlying genetic cause for a unifying diagnosis was pursued. Genomic DNA of the siblings affected by FH with biopsy‑proven FSGS was analyzed, and their father was screened for 18 gene mutations associated with FSGS [nephrin, podocin, CD2 associated protein, phospholipase C ε, actinin α 4, transient receptor potential cation channel subfamily C member 6, inverted formin, FH2 and WH2 domain containing, Wilms tumor 1, LIM homeobox transcription factor 1 β, laminin subunit β 2, laminin subunit β 3, galactosida α, integrin subunit β 4, scavenger receptor class B member 2, coenzyme Q2, decaprenyl diphosphate synthase subunit 2, mitochondrially encoded tRNA leucine 1 (UUA/G; TRNL1) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1] using matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry technology. Then whole exome sequencing (WES) was performed in the two probands to ascertain whether there were other known or unknown gene mutations that segregated with the disease. Using mass array technology, a TRNL1 missense homozygous mutation (m. 3290T>C) was identified in the probands diagnosed with FH and manifested as FSGS on biopsy. In addition, a COL4A4 missense mutation c. 4195A>T (p. M1399L) in heterozygous pattern was identified using WES. None of these variants were detected in their father. In the present study, a mutation in TRNL1 (m. 3290T>C) was identified, which was the first reported variant associated with FSGS. The COL4A4 (c. 4195A>T) may co‑segregate with FSGS. Screening for COL4A mutations in familial FSGS patients is suggested in the present study. Genetic investigations of families with similar clinical phenotypes should be a priority for nephrologists. The combination of mass array technology and WES may improve the detection rate of genetic mutation with a high level of accuracy.

The Subthalamic Neurons are Activated by Both Orexin-A and Orexin-B.

The subthalamic nucleus is an important nucleus in the indirect pathway of the basal ganglia circuit and therefore is involved in motor control under both normal and pathological conditions. Morphological studies reveal that the subthalamic nucleus receives relatively dense orexinergic projections originating from the hypothalamus. Both orexin-1 (OX1) and orexin-2 (OX2) receptors are expressed in the subthalamic nucleus. To explore the functions of orexinergic system in the subthalamic nucleus, extracellular electrophysiological recordings and behavioral tests were performed in the present study. Exogenous application of orexin-A significantly increased the spontaneous firing rate from 5.70 ± 0.66 Hz to 9.87 ± 1.18 Hz in 64.00% subthalamic neurons recorded. OX1 receptors are involved in orexin-A-induced excitation. Application of orexin-B increased the firing rate from 7.47 ± 0.92 Hz to 11.85 ± 1.39 Hz in 80.95% subthalamic neurons recorded, entirely through OX2 receptors. Both OX1 and OX2 receptor antagonists decreased the firing rate in 43.75% and 62.50% subthalamic neurons recorded respectively, suggesting the involvement of endogenous orexinergic system in the control of spontaneous firing activity. Further elevated body swing test revealed that microinjection of orexins and the receptor antagonists into the subthalamic nucleus induced contralateral-biased swing and ipsilateral-biased swing, respectively. Taken together, the present study suggests that orexins play important roles in the subthalamic nucleus which may provide further evidence for the involvement of subthalamic orexinergic tone in Parkinson's disease.

A native-like bispecific antibody suppresses the inflammatory cytokine response by simultaneously neutralizing tumor necrosis factor-alpha and interleukin-17A.

Anti-tumor necrosis factor (TNF) therapies are successful in the treatment of inflammatory disorders. However, some patients with rheumatoid arthritis (RA) fail to response anti-TNF drugs due to the compensation of other inflammatory signals. In this study, to reduce compensatory responses of interleukin-17A (IL-17A) during TNF-α inhibition, we generated an IgG-like bispecific antibodiy (bsAb) against TNF-α and IL-17A through a combination method of electrostatic Fc pairing and light chain crossover. This bsAb exhibited relatively high stability comparable to natural IgG antibodies, and retained the unaltered affinities to both of two targets. BsAb significantly decreased not only the expression level of neutrophil or Th17 chemokines, but also the secretion of IL-6/IL-8 on fibroblast-like synoviocytes (FLS) from a patient with RA. Meanwhile, TNF-α-mediated cellular cytotoxicity of fibroblasts was neutralized by bsAb. Importantly, we demonstrate that the combined blockade of TNF-α and IL-17A is more efficient than inhibition of either factor alone. Our results suggest the IgG-like anti-TNF-α/IL-17A bispecific molecule overcome the limited therapeutic responses using anti-TNF drugs. It may be a promising therapeutic agent for the treatment of autoimmune diseases.

A case report of recurrent thyroid inflammatory myofibroblastic tumor and its metastasis in soft tissue.

Inflammatory myofibroblastic tumor (IMT) is a neoplasm of low malignant potential. The most frequent site of IMT is in the lung, whereas recurrent and metastasis of thyroid IMT has been seldom reported.

High Levels of GSK-3β Signaling Reduce Osteogenic Differentiation of Stem Cells in Osteonecrosis of Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a common but intractable disease. In this study, we investigated the mechanisms regulating alterations in mesenchymal stem cell (MSC) differentiation in ONFH. Five patients who were diagnosed with ONFH were enrolled in this study. BMSCs were isolated from the osteonecrotic zone in the femoral head (FH-pMSCs) and from the normal zone in the pelvis (hMSCs) of the same patient. Morphology, cell proliferation, and expression of mediators of the Wnt signaling pathway were evaluated. There were significant differences in cell proliferation and expression of surface markers between the two populations of cells. FH-pMSCs exhibited significantly lower osteogenic differentiation compared to hMSCs (p < 0.0001). Dissection of the Wnt pathway showed that FH-pMSCs had significantly higher GSK3β expression compared to hMSCs (p < 0.001). Addition of LiCl, a GSK3β inhibitor, significantly increased osteogenic differentiation in FH-pMSCs, suggesting a relationship between the microenvironment and regulation of stem cell behavior in ONFH. FH-pMSCs also exhibited significant downregulation of other mediators of the Wnt signaling pathway, including runx2 and β-catenin. Our data suggested that mediators of the Wnt signaling pathway, such as GSK3β could be important therapeutic targets for early-stage ONFH.

Pathways from Hiv-Related Stigma to Antiretroviral Therapy Measures in The Hiv Care Cascade for Women Living with Hiv in Canada.

Associations between HIV-related stigma and reduced anti-retroviral (ART) adherence are widely established, yet the mechanisms accounting for this relationship are underexplored. There has been less attention to HIV-related stigma and its associations with ART initiation and current ART use. We examined pathways from HIV-related stigma to ART initiation, current ART use, and ART adherence among women living with HIV in Canada.

Tailoring two-dimensional nanoparticle arrays into various patterns.

A simple and effective technique has been developed to fabricate patterns of nanoparticle arrays. Lithographically fabricated structures in resists serve as scissors to tailor two-dimensional (2D) nanoparticle arrays on a flat poly(dimethylsiloxane) (PDMS) stamp. The desired patterns of nanoparticle arrays remaining on the PDMS stamp after tailoring can be printed onto solid substrates. Various regular nanoparticle patterns, such as squares, triangles, disks, and pentagons, can be easily prepared using this technique. Arbitrary nanoparticle patterns as complex as Chinese characters have been successfully demonstrated. Moreover, nanoparticle stripes with width ranging from micrometers to quasi single nanoparticle diameter have also been achieved. Nanoparticle stripes have been integrated into electronic devices for transport measurements.

Knot soliton in DNA and geometric structure of its free-energy density.

In general, the geometric structure of DNA is characterized using an elastic rod model. The Landau model provides us a new theory to study the geometric structure of DNA. By using the decomposition of the arc unit in the helical axis of DNA, we find that the free-energy density of DNA is similar to the free-energy density of a two-condensate superconductor. By using the φ-mapping topological current theory, the torus knot soliton hidden in DNA is demonstrated. We show the relation between the geometric structure and free-energy density of DNA and the Frenet equations in differential geometry theory are considered. Therefore, the free-energy density of DNA can be expressed by the curvature and torsion of the helical axis.

Effects of Melatonin Levels on Neurotoxicity of the Medial Prefrontal Cortex in a Rat Model of Parkinson's Disease.

Damage of the medial prefrontal cortex (mPFC) results in similar characteristics to the cognitive deficiency seen with the progress of Parkinson's disease (PD). Since the course of mPFC damage is still unclear, our study aimed to investigate the effects of melatonin (MT) on neurotoxicity in the mPFC of a rat model of PD.

Deep RNA Sequencing Uncovers a Repertoire of Human Macrophage Long Intergenic Noncoding RNAs Modulated by Macrophage Activation and Associated With Cardiometabolic Diseases.

Sustained and dysfunctional macrophage activation promotes inflammatory cardiometabolic disorders, but the role of long intergenic noncoding RNA (lincRNA) in human macrophage activation and cardiometabolic disorders is poorly defined. Through transcriptomics, bioinformatics, and selective functional studies, we sought to elucidate the lincRNA landscape of human macrophages.