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Ke Yang - Top 30 Publications

A New Maraging Stainless Steel with Excellent Strength-Toughness-Corrosion Synergy.

A new maraging stainless steel with superior strength-toughness-corrosion synergy has been developed based on an innovative concept of alloy design. The high strength-toughness combination is achieved by forming dispersive nano-sized intermetallic compounds in the soft lath martensitic matrix with a slight amount of residual austenite. The good corrosion resistance is guaranteed by exactly controlling the Co content based on understanding the synergistic effect between Co and Cr. The fine structure characteristics of two dominant strengthening precipitations including Ni₃Ti and Mo-rich phases were finely characterized associated with transmission electron microscope (TEM) and atom probe tomography (APT) analyses. The relationship among microstructure, strength and toughness is discussed. The precipitation mechanism of different precipitates in the new maraging stainless steel is revealed based on the APT analysis.

Terahertz spectroscopy for the isothermal detection of bacterial DNA by magnetic bead-based rolling circle amplification.

The demand for rapid and sensitive bacterial detection is continuously increasing due to the significant requirements of various applications. In this study, a terahertz (THz) biosensor based on rolling circle amplification (RCA) was developed for the isothermal detection of bacterial DNA. The synthetic bacterium-specific sequence of 16S rDNA hybridized with a padlock probe (PLP) that contains a sequence fully complementary to the target sequence at the 5' and 3' ends. The linear PLP was circularized by ligation to form a circular PLP upon recognition of the target sequence; then the capture probe (CP) immobilized on magnetic beads (MBs) acted as a primer to initialize RCA. As DNA molecules are much less absorptive than water molecules in the THz range, the RCA products on the surface of the MBs cause a significant decrease in THz absorption, which can be sensitively probed by THz spectroscopy. Our results showed that 0.12 fmol of synthetic bacterial DNA and 0.05 ng μL(-1) of genomic DNA could be effectively detected using this assay. In addition, the specificity of this strategy was demonstrated by its low signal response to interfering bacteria. The proposed strategy not only represents a new method for the isothermal detection of the target bacterial DNA but also provides a general methodology for sensitive and specific DNA biosensing using THz spectroscopy.

Comparison of hydrophobic and hydrophilic intraocular lens in preventing posterior capsule opacification after cataract surgery: An updated meta-analysis.

Posterior capsular opacification (PCO) is a common long-term complication of cataract surgery. Intraocular lens design and material have been implicated in influencing the development of PCO. This study evaluated the association of hydrophobic and hydrophilic intraocular lenses on preventing PCO.

Label-free sensing of the binding state of MUC1 peptide and anti-MUC1 aptamer solution in fluidic chip by terahertz spectroscopy.

The aptamer and target molecule binding reaction has been widely applied for construction of aptasensors, most of which are labeled methods. In contrast, terahertz technology proves to be a label-free sensing tool for biomedical applications. We utilize terahertz absorption spectroscopy and molecular dynamics simulation to investigate the variation of binding-induced collective vibration of hydrogen bond network in a mixed solution of MUC1 peptide and anti-MUC1 aptamer. The results show that binding-induced alterations of hydrogen bond numbers could be sensitively reflected by the variation of terahertz absorption coefficients of the mixed solution in a customized fluidic chip. The minimal detectable concentration is determined as 1 pmol/μL, which is approximately equal to the optimal immobilized concentration of aptasensors.

Research of Characteristics of Stimulation Methods and Application of Acupoint in Auricular Needle Therapy Based on Data Mining.

In the present paper, using data mining technology,the authors downloaded information from databases on auricular needle therapy, and obtained data samples from journals and academic dissertations involving the application of auricular needle therapy to treat diseases, and then screened, audited, and extracted the data and performed a statistical analysis. The authors extracted data on the application of auricular needle therapy in the stimulation methods of medicine (needling instrument), selection of the side of ear to treat disease and the number of times the ear was pressed per day and the compression time. In the stimulation methods, the needling instrument varied, the seeds of cowherb Semen Vaccariae were applied in 60.89% of the total stimulation methods. The number of times the ear was pressed per day and the compression time in the clinic were optional. The main points in auricular needle therapy were the contralateral side; there was no significant difference in the effect of a single side or both sides of the ear to treat disease.

Anti-fibrotic function of Cu-bearing stainless steel for reducing recurrence of urethral stricture after stent implantation.

Recurrent stenosis is the main reason inducing the failure of urethral stricture treatment. Our previous study has found that the 316L type Cu bearing stainless steel (316L-Cu SS) showed antimicrobial activity and anti-encrustation performance when it was used for relieving urethral obstructer. However, whether it can reduce the occurrence of fibrosis or not, we need further investigation to compare the cellular and molecular responses of human urethral scar fibroblast cells (USFCs) on 316L-Cu SS and medical grade 316L stainless (316L SS, as a control). [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)- 2H-tetrazolium (MTS) and Transwell were used to assess the cellular responses, which confirmed that 316L-Cu SS could inhibit proliferation and migration of USFCs. Molecular expressions of fibrosis were evaluated by western blot, real-time quantitative polymerase chain reaction (qPCR), and Cu/Zn superoxide dismutase (CuZnSOD) measurement. The results indicated that up-regulating of CuZnSOD attenuated the transforming growth factor-β1 expression and phosphorylation of Smad3 after exposure to 316L-Cu SS. Besides, the content of collagen type I (COL1) and collagen type III (COL3) secreting into the culture medium measured by enzyme-linked immunosorbent assay were in accord with the results of messenger ribonucleic acids. Both of them exhibited lower levels of COL1/COL3 exposure to 316L-Cu SS, demonstrating the inhibitory performance of 316L-Cu SS against fibrosis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017.

Two single-point mutations shift the ligand selectivity of a pheromone receptor between two closely related moth species.

Male moths possess highly sensitive and selective olfactory systems that detect sex pheromones produced by their females. Pheromone receptors (PRs) play a key role in this process. The PR HassOr14b is found to be tuned to (Z)-9-hexadecenal, the major sex-pheromone component, in Helicoverpa assulta. HassOr14b is co-localized with HassOr6 or HassOr16 in two olfactory sensory neurons within the same sensilla. As HarmOr14b, the ortholog of HassOr14b in the closely related species Helicoverpa armigera, is tuned to another chemical (Z)-9-tetradecenal, we study the amino acid residues that determine their ligand selectivity. Two amino acids located in the intracellular domains F232I and T355I together determine the functional difference between the two orthologs. We conclude that species-specific changes in the tuning specificity of the PRs in the two Helicoverpa moth species could be achieved with just a few amino acid substitutions, which provides new insights into the evolution of closely related moth species.

C6 glioma-conditioned medium induces malignant transformation of mesenchymal stem cells: Possible role of S100B/RAGE pathway.

Mesenchymal stem cells (MSCs) have been widely studied as an attractive therapeutic agent for the treatment of tumors. However, the adverse effects of the tumor paracrine factors who affect MSCs are still unclear. In this study, we report for the first time that C6 glioma-conditioned medium (GCM) induces malignant transformation of MSCs. In contrast to MSCs, the transformed mesenchymal stem cells (TMCs) exhibited tumor cell characterizations in vitro and highly tumorigenic in vivo. Furthermore, GCM and recombinant S100B increased receptor for advanced glycation end products (RAGE) and its downstream Akt1, STAT3 genes expression as well as phosphorylation and transcriptional activation. Finally, blockage of S100B-RAGE interaction by RAGE inhibitor FPS-ZM1 attenuated GCM and S100B-induced Akt1, STAT3 activation, abolished its cell proliferation, migration and invasion actions. Together, these results suggest that the RAGE pathway may play a possible role in malignant transformation procedure of MSCs, and that this process may be mediated through S100B.

Mutation landscape and intra-tumor heterogeneity of two MANECs of the esophagus revealed by multi-region sequencing.

Mixed adenoneuroendocrine carcinoma (MANEC) in the esophagus is an infrequent but highly malignant cancer with few known genomic alterations. We conducted whole-exome sequencing and whole-genome SNP genotyping for 4-6 tumor subregions and 5-6 adjacent normal tissue sites and 1-3 lymph node metastases in two esophageal MANECs to detect somatic mutations and copy number alterations, and to explore their spatial heterogeneity and underlying clonal structure. TP53 mutation, RB1 deletion or LOH, and PIK3CA, PTEN, KRAS, SOX2, DVL3, TP63 amplification appeared in all regions in both tumors. Mutations falling in known cancer genes tended to show higher variant allele frequencies than those not falling in these genes in at least one of the cases. Phylogenetic analyses of the samples and underlying subclones suggested extensive migration across different tumor regions and from some regions to the lymph nodes. Lymph node metastases appeared to have been seeded by both early founder cells as well as subsequent, locally emerging daughter clones. A phenotypically normal tissue site carried most of the mutations found in neighboring tumor samples, implying field cancerization. Understanding such complex genetic heterogeneity within each patient will be important for guiding clinical decisions.

Highly luminescent nitrogen-doped carbon dots for simultaneous determination of chlortetracycline and sulfasalazine.

Here, we have presented a green and facile strategy to fabricate nitrogen-doped carbon dots (N-CDs) and their applications for determination of chlortetracycline (CTC) and sulfasalazine (SSZ). The fluorescent N-CDs, prepared by one-step hydrothermal reaction of citric acid and l-arginine, manifested numerous excellent features containing strong blue fluorescence, good water-solubility, narrow size distribution, and a high fluorescence quantum yield (QY) of 38.8%. Based on the fluorescence quenching effects, the as-synthesized N-CDs as a fluorescent nanosensor exhibited superior analytical performances for quantifying CTC and SSZ. The linear range for CTC was calculated to be from 0.85 to 20.38 μg ml(-1) with a low detection limit of 0.078 μg ml(-1) . Meanwhile, the linear range for SSZ was estimated to be from 0.34 to 6.76 μg ml(-1) with a low detection limit of 0.032 μg ml(-1) . Therefore, the N-CDs hold admirable application potential for constructing a fluorescent sensor for pharmaceutical analysis.

Glycated Apolipoprotein A-IV Induces Atherogenesis in Patients With CAD in Type 2 Diabetes.

Nonenzymatic glycation of apolipoproteins plays a role in the pathogenesis of the vascular complications of diabetes.

In vitro study of stimulation effect on endothelialization by a copper bearing cobalt alloy.

Endothelialization is an important process after stenting in coronary artery. Recovery of the injured site timely can reduce the neointima formation and platelet absorbance, leading to a lower risk of in-stent restenosis. Copper is known to be critical in vascular construction. Thus a combination of copper with stent materials is a meaningful attempt. A copper bearing L605-Cu cobalt alloy was prepared and its effect on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro in this study. It was found that HUVECs attached and stretched better on the surface of L605-Cu compared with L605, and the apoptosis of cells was decreased simultaneously. The migration and tube formation of HUVECs were also enhanced by the extract of L605-Cu. Furthermore, L605-Cu increased the mRNA expression of VEGF in HUVECs significantly. However it had no effect on the secretion of NO or mRNA expression of eNOS. The result of blood clotting test indicated that L605-Cu had better blood compatibility. These results above have demonstrated that the L605-Cu alloy is promising to be a new stent material with function of accelerating endothelialization. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2017.

Phenotypic and genetic analysis of a child carrying a 17q11.2 microdeletion.

To analyze a child with facial abnormalities with combined cytogenetic and molecular techniques and delineate its clinical phenotype.

Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein.

Neuregulin receptor degradation protein-1 (Nrdp1) is an E3 ubiquitin ligase that targets proteins for degradation and regulates cell growth, apoptosis and oxidative stress in various cell types. We have previously shown that Nrdp1 is implicated in ischemic cardiomyocyte death. In this study, we investigated the change of Nrdp1 expression in ischemic neurons and its role in ischemic neuronal injury. Primary rat cerebral cortical neurons and pheochromocytoma (PC12) cells were infected with adenoviral constructs expressing Nrdp1 gene or its siRNA before exposing to oxygen-glucose deprivation (OGD) treatment. Our data showed that Nrdp1 was upregulated in ischemic brain tissue 3 h after middle cerebral artery occlusion (MCAO) and in OGD-treated neurons. Of note, Nrdp1 overexpression by Ad-Nrdp1 enhanced OGD-induced neuron apoptosis, while knockdown of Nrdp1 with siRNA attenuated this effect, implicating a role of Nrdp1 in ischemic neuron injury. Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8) in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions. In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect.

Multiregional sequencing reveals genomic alterations and clonal dynamics in primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus (PMME) is a rare and aggressive disease with high tendency of metastasis. To characterize the genetic basis and intra-tumor heterogeneity of PMME, we performed multiregion exome sequencing and whole genome SNP array genotyping of 12 samples obtained from a PMME patient. High intra-tumor heterogeneity was observed in both somatic mutation and copy number alteration levels. Nine geographically separate samples including two normal samples were clonally related and followed a branched evolution model. Most putative oncogenic drivers such as BRAF and KRAS mutations as well as CDKN2A biallelic inactivation were observed in trunk clones, whereas clinically actionable mutations such as PIK3CA and JAK1 mutations were detected in branch clones. Ancestor tumor clones evolved into three subclonal clades: clade1 fostered metastatic subclones that carried metastatic features of PIK3CA and ARHGAP26 point mutations as well as chr13 arm-level deletion, clade2 owned branch-specific JAK1 mutations and PTEN deletion, and clade3 was found in two vertical distribution samples below the primary tumor area, highlighting the fact that it is possible for PMME to disseminate by the submucosal longitudinal lymphatic route at an early stage of metastasis. These findings facilitate interpretation of the genetic essence of this rare melanoma subtype as well as the pattern of cancer evolution, thus reinforcing the therapeutic challenges associated with PMME.

Carbohydrate metabolism and gene regulation during anther development in an androdioecious tree, Tapiscia sinensis.

Tapiscia sinensis (Tapisciaceae) is a functional androdioecious species with both male and hermaphroditic individuals, and fruit ripening overlaps with flowering in the hermaphroditic individuals. Pollen vitality was lower in the hermaphrodites than in the males. Anther development requires nutrients, and carbohydrates are the basic nutrients; abnormal carbohydrate metabolism will result in pollen abortion. The aim of this research was to gain insight into the relationship between carbohydrate metabolism and the weakening of the male function of hermaphroditic flowers in T. sinensis.

Incidence and clearance of oral human papillomavirus infection: A population-based cohort study in rural China.

The natural history of oral human papillomavirus (HPV) infection which is linked with the increased incidence of oropharyngeal squamous cell cancer (OPSCC) has been incompletely studied. Oral swab specimens and questionnaire data were obtained bi-annually for up to 6 visits from 4314 healthy adults aged 25-69 in rural Anyang, China. HPV infection status was evaluated with PCR-based sequencing. Participants with at least two consecutive valid HPV results within the study period were included in the incidence and clearance analysis. Among 3289 participants included in this analysis (median follow-up time 18.3 months), incidence rates of mucosal HPV, oncogenic mucosal HPV and cutaneous HPV were 0.53 (95% CI: 0.39-0.73), 0.30 (95% CI: 0.20-0.46), and 4.17 (95% CI: 3.70-4.70) per 1,000 person-months respectively. Most newly acquired infections were cleared within one year. Recent practice of oral sex increased the risk of incident infection with mucosal HPV (Adjusted HR, 5.03; 95% CI, 1.16-21.73) and oncogenic mucosal HPV (Adjusted HR, 10.13; 95% CI, 2.14-48.06). Newly acquired oral mucosal HPV infections are rare and most are cleared within one year in rural Chinese. This study expands understanding of the natural history of oral HPV in countries with a lower incidence of HPV-OPSCC.

Transcriptome analysis of Rana chensinensis liver under trichlorfon stress.

Trichlorfon is a selective organophosphate insecticide that is widely applied in aquaculture and agriculture for control of various parasites. However, repeated and excess applications of trichlorfon often lead to water pollution and threaten non-targeted species. Our previous studies showed that trichlorfon could cause oxidative stress, lipid peroxidation and hepatic lesions in the liver of Rana chensinensis, but the related molecular mechanisms remain unclear. To explore the interference of trichlorfon in gene transcription, the differentially expressed genes in the liver of R. chensinensis exposed to trichlorfon were characterized using the RNA-seq platform. A search of all unigenes against non-redundant protein sequence (Nr), non-redundant nucleotide (Nt), Swiss-Prot, Kyoto Encyclopaedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG) and Gene Ontology (GO) databases resulted in 22,888, 21,719, 20,934, 16,923, 7375 and 15,631 annotations, respectively, and provided a total of 27,781 annotated unigenes. Among the annotated unigenes, 16,923 were mapped to 257 signalling pathways. A set of 3329 differentially expressed unigenes was identified by comparison of the two groups in liver. Notably, relative expression of metabolism-related genes, including both up- and down-regulated genes, were also validated by qPCR. The present study depicts the high degree of transcriptional complexity in R. chensinensis under trichlorfon stress and provides new insights into the molecular mechanisms of organophosphate insecticide toxicology. Some of these metabolism-responsive genes could be useful for understanding the toxicological mechanism of trichlorfon on non-target aquatic organisms and will contribute to the conservation of aquatic life.

Ion channel functional protein kinase TRPM7 regulates Mg ions to promote the osteoinduction of human osteoblast via PI3K pathway: In vitro simulation of the bone-repairing effect of Mg-based alloy implant.

Mg-based alloys, as the potential orthopaedic implant, can self-degrade to avoid second operation for its remove, and enable to promote bone repair; however, the underlying molecular mechanisms remain unclear. In the present study, we examined the effect of Mg ions on osteogenesis, chemotaxis and anti-alkaline stress in hFOB1.19 human osteoblast cells to simulate bone-repairing effect of a biodegradable Mg-based alloy implant in vitro, and explored the regulatory role of the transient receptor potential melastatin 7 (TRPM7)/phosphoinositide 3-kinase (PI3K) signalling pathway in the process of Mg ion-induced bone repair by knockdown of TRPM7 and antagonizing PI3K activity. Results indicate that Mg ions up-regulated the expression of Runx2 and alkaline phosphatase (ALP) through TRPM7/PI3K signalling pathway, which could significantly enhance the osteogenic activity of human osteoblasts. Furthermore, the expression levels of MMP2, MMP9 and vascular endothelial growth factor (VEGF) were increased by TRPM7/PI3K signalling pathway, which recruits osteoblasts from low- to high-Mg ion environments by inducing cell migration. Although an alkaline environment has antibacterial effects, alkaline stress can cause cytotoxicity and induce cell death. Finally, we found that Mg ions could activate PI3K phosphorylation to promote cell growth and survival, protecting cells against the alkaline-stress-induced cytotoxicity caused by the degradation of Mg-based alloy implants. Our study not only revealed the molecular mechanism of Mg in promoting bone repair but also explained the protective effects of Mg ions on osteoblasts in an alkaline environment, which provides a theoretical basis and new directions for the application of Mg-based alloy implant material in orthopaedics fixations and osteosarcoma treatment.

A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease.

Late-onset Pompe disease is a rare genetic neuromuscular disorder caused by lysosomal acid alpha-glucosidase (GAA) deficiency that ultimately results in mobility loss and respiratory failure. Current enzyme replacement therapy with recombinant human (rh)GAA has demonstrated efficacy in subjects with late-onset Pompe disease. However, long-term effects of rhGAA on pulmonary function have not been observed, likely related to inefficient delivery of rhGAA to skeletal muscle lysosomes and associated deficits in the central nervous system. To address this limitation, reveglucosidase alfa, a novel insulin-like growth factor 2 (IGF2)-tagged GAA analogue with improved lysosomal uptake, was developed. This study evaluated the pharmacokinetics, safety, and exploratory efficacy of reveglucosidase alfa in 22 subjects with late-onset Pompe disease who were previously untreated with rhGAA.

Evaluation of PDQ-8 and its relationship with PDQ-39 in China: a three-year longitudinal study.

Parkinson's disease is characterized by motor and non-motor symptoms with wide ranging impacts on the health-related quality of life. The 39-item Parkinson's disease Questionnaire (PDQ-39) is the most widely used PD-specific health-related quality-of-life questionnaire. The short-form 8-item Parkinson's disease Questionnaire (PDQ-8) was found to produce results similar to that of the PDQ-39 cross-culturally. However, there is no evaluation of the PDQ-8 in the mainland of China.

Hard templating ultrathin polycrystalline hematite nanosheets: effect of nano-dimension on CO2 to CO conversion via the reverse water-gas shift reaction.

Understanding how nano-dimensionality impacts iron oxide based catalysis is central to a wide range of applications. Here, we focus on hematite nanosheets, nanowires and nanoparticles as applied to catalyze the reverse water gas shift (RWGS) probe reaction. We introduce a novel approach to synthesize ultrathin (4-7 nm) hematite nanosheets using copper oxide nanosheets as a hard template and propose a reaction mechanism based on density functional theory (DFT) calculations. Hematite nanowires and nanoparticles were also synthesized and characterized. H2 temperature programmed reduction (H2-TPR) and RWGS reactions were performed to glean insights into the mechanism of CO2 conversion to CO over the iron oxide nanomaterials and were compared to H2 binding energy calculations based on density functional theory. While the nanosheets did exhibit high CO2 conversion, 28% at 510 °C, we found that the iron oxide nanowires had the highest CO2 conversion, reaching 50% at 750 °C under atmospheric pressure. No products besides CO and H2O were detected.

A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome.

Perrault syndrome is a rare multisystem disorder that manifests with sensorineural hearing loss in both sexes, primary ovarian insufficiency in females and neurological features. The syndrome is heterogeneous both genetically and phenotypically.

Attenuation of TNF-α-Induced Inflammatory Injury in Endothelial Cells by Ginsenoside Rb1 via Inhibiting NF-κB, JNK and p38 Signaling Pathways.

It is currently believed that inflammation plays a central role in the pathophysiology of atherosclerosis. Oxidative stress and redox-sensitive transcription factors are implicated in the process. Ginsenoside Rb1, a major active ingredient in processed Radix notoginseng, has attracted widespread attention because of its potential to improve cardiovascular function. However, the effects of ginsenoside Rb1 on tumor necrosis factor-α (TNF-α)-induced vascular endothelial cell injury and the underlying molecular mechanisms have never been studied. This study showed that TNF-α-induced oxidative stress, inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) could be attenuated by ginsenoside Rb1 pretreatment. Using JC-1, Annexin V/PI and TUNEL staining, and a caspase-3 activity assay, we found that Rb1 provided significant protection against TNF-α-induced cell death. Furthermore, Rb1 pretreatment could inhibit TNF-α-induced ROS and MDA production; increase the activities of SOD, CAT, and GSH-Px; and decrease the levels of IL-1β, IL-6, VCAM-1, ICAM-1, VEGF, MMP-2 and MMP-9. Importantly, the cytoprotective effects of Rb1 were correlated with NF-κB signaling pathway inhibition. Additionally, we found that Rb1 may suppress the NF-κB pathway through p-38 and JNK pathway activation, findings supported by the results of our experiments involving anisomycin (AM), a JNK and p38 activator. In conclusion, this study showed that ginsenoside Rb1 protects HUVECs from TNF-α-induced oxidative stress and inflammation by inhibiting JNK and p38. This inhibition suppressed NF-κB signaling and down-regulated the expression of inflammatory factors and apoptosis-related proteins.

The algicidal mechanism of prodigiosin from Hahella sp. KA22 against Microcystis aeruginosa.

In recent years, Microcystis aeruginosa blooms have occurred throughout the world, causing huge economic losses and destroying aquatic ecosystems. It is necessary to develop effective and ecofriendly methods to control M. aeruginosa blooms. Here, we report a high algicidal activity of prodigiosin (PG) against M. aeruginosa as well as the algicidal mechanism. PG showed high algicidal activity against M. aeruginosa, with a 50% lethal dose (LD50) of 5.87 μg/mL in 72 h. A combination of methods, including propidium iodide and Annexin V-fluorescein staining assays and light and electron microscopy indicated the existence of two modes of cell death with features similar to those in eukaryotic programmed cell death: necrotic-like and apoptotic-like. Biochemical and physiological analyses showed that PG generates reactive oxygen species (ROS), which induce lipid peroxidation, damage the membrane system and destroy the function of the photosystem. A proteomics analysis revealed that many proteins were differentially expressed in response to PG stress and that most of these proteins were involved in important metabolic processes, which may trigger necrotic-like or apoptotic-like cell death. The present study sheds light on the multiple toxicity mechanisms of PG on M. aeruginosa and its potential for controlling the occurrence of M. aeruginosa blooms in lakes.

Mkit: A cell migration assay based on microfluidic device and smartphone.

Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS(2) technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS(2) technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS(2)-based cell functional assay for testing cell migration (the Mkit). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the Mkit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the Mkit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the Mkit. In addition to research applications, we demonstrated the effective use of the Mkit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed Mkit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications.

Serum amyloid A enrichment impairs the anti-inflammatory ability of HDL from diabetic nephropathy patients.

Impaired anti-inflammatory ability of high-density lipoprotein (HDL) has been demonstrated in patients with type-2 diabetes mellitus (T2DM). However, whether HDL from patients with diabetic nephropathy (DN) suffers additional damage remains unknown. This study compared the anti-inflammatory capacities of HDL from healthy controls, T2DM patients with normal renal function, and T2DM patients with DN.

Potential energy surfaces of quintet and singlet O4.

We present global ground-state potential energy surfaces for the quintet and singlet spin states of the O4 system that are suitable for treating high-energy vibrational-rotational energy transfer and collision-induced dissociation in electronically adiabatic, spin-conserving O2-O2 collisions. The surfaces are based on MS-CASPT2/maug-cc-pVTZ electronic structure calculations with scaled external correlation. The active space has 16 electrons in 12 orbitals. The calculations cover nine kinds of geometrical arrangements corresponding to dissociative diatom-diatom collisions of O2, geometries corresponding to O3-O, geometries identified by running trajectories, and geometries along linear synchronous transit paths. The global ground-state potential energy surfaces were obtained by a many-body approach with an accurate O-O pairwise interaction and a fit of the many-body interaction to 12 684 electronic structure data points for the singlet and 10 543 electronic structure data points for the quintet. The many-body fit is based on permutationally invariant polynomials in terms of bond-order functions of the six interatomic distances; the bond-order functions are mixed exponential-Gaussian functions.

Pressure-Induced Crystallization and Phase Transformation of Para-xylene.

Static pressure is an alternative method to chemical pressure for tuning the crystal structure, bonds, and physical properties of materials, and is a significant technique for the synthesis of novel materials and fundamental research. In this letter, we report the crystallization and phase transformation of p-xylene under high pressure. Our optical micrographic observations and the appearance of lattice modes in the Raman and infrared (IR) spectra indicated that p-xylene crystallizes at ∼0.1 GPa. The X-ray diffraction (XRD) pattern at 0.84 GPa suggests that the crystallized p-xylene had a monoclinic phase with the Cc(9) space group. The sharp shrinkage of the lattice at ~13 GPa and the solid state of the decompressed sample we observed suggests a new crystalline phase of p-xylene. The in situ XRD showed that the new crystalline phase was still a monoclinic structure but with a different space group of C2(5), indicating that a phase transition occurred during further compression. The mass spectrometry experiment confirmed phase transition polymerization, with mainly trimer and tetramer polymers. Our findings suggest an easy and efficient method for crystallizing and polymerizing p-xylene under high pressure.

Wild‑type blocking pcr coupled with internal competitive amplified fragment improved the detection of rare mutation of KRAS.

Mutant KRAS proto‑oncogene GTPase (KRAS) serves an important role in predicting the development, diagnosis, treatment and efficacy of targeted drug therapies for colorectal cancer. To improve the detection efficacy of trace amount of mutant KRAS, the locked nucleic acid‑based method was modified in the present study. Internal competitive amplification fragments were used to improve the inhibition of wild‑type KRAS with a wild‑type blocking (WTB) probe and specifically amplify the trace amounts of mutant KRAS. The modified method, quantitative clamp‑based polymerase chain reaction technology using WTB coupled with internal competitive reference to enhance the amplification specificity, named WIRE‑PCR, completely blocked the amplification of wild‑type KRAS in 50‑150 ng DNA templates. The added internal competitive amplified fragments were amplified together with the target gene, which were used to reduce base mismatch due to the high number of cycles in PCR and quantify the total amount of DNA. The results demonstrated that WIRE‑PCR facilitated the detection of mutated alleles at a single molecular level. In the colorectal biopsies from 50 patients with suspected colorectal cancer, 18 cases (36%) contained mutant KRAS, and the amount of mutant DNA accounted for 18.6‑64.2% of the total DNA. WIRE‑PCR is a simple, rapid and low‑cost quantitative analysis method for the detection of trace amounts of the mutant KRAS.