Preparation of high-resolution micro/nano dot array by electrohydrodynamic jet printing with enhanced uniformity.

The high-resolution array is the basic structure of most kinds of microelectronics. Electrohydrodynamic jet (E-Jet) printing technology is widely applied in manufacturing array structures with high resolution, high material compatibility and multi-modal printing. It is still challenging to acquire high uniformity of printed array with micro-nanometer resolution, which greatly influences the performance and lifetime of the microelectronics. In this paper, to improve the uniformity of the printed array, the influence of each parameter on the uniformity of the E-jet printed dot array is studied on the cobuilt NEJ-E/P200 experimental platform, finding the applied voltage plays the most important role in maintaining the uniformity of the printed array. By appropriately adjusting the printing parameters, the dot arrays with different resolutions from 500 pixels per inch (PPI) to 17,000 PPI are successfully printed. For arrays below and over 10,000 PPI, the deviations of the uniformity are within 5% and 10% respectively. In this work, the dot array over 15,000 PPI is first implemented using E-jet printing. The conclusions acquired by experimental analysis of dot array printing process are of great importance in high resolution array printing as it provides practical guidance for parameters adjustment.

Lattice Boltzmann Study of Microdroplet Evaporation Process in Pixel Pits.

Inkjet printing has the advantages of high material utilization, low cost, and large-area production and is a promising manufacturing technology for organic light-emitting diode (OLED) displays. However, the droplet evaporation in micron-size pixel pits is highly influenced by the pit wall. Such a process is extremely difficult to control, leading to the appearance of defects such as the coffee ring in the printing process of OLED displays. In this work, a multiphase thermal lattice Boltzmann (LB) model based on multiple distribution functions is established to study the evaporation process of micron-size droplets in pits. According to the characteristics of the largest number of the three-phase contact line (TCL) appearing in the evaporation process, the evaporation modes can be divided into three types, i.e., one, two, and three TCLs. In the 1-TCL mode, the droplet stays in constant contact radius (CCR) for the shortest time; in 2-TCL and 3-TCL modes, the liquid film fracture behavior of evaporating droplets in the pit is well captured. The effects of the pit height and the contact angle on the droplet evaporation mode are investigated in detail. The phase diagrams of evaporation modes with different parameters are also established. The revealed evaporation mechanism is supposed to be useful for regulating the droplet evaporation behavior and controlling the cured film shape in the OLED printing process.

A high-adaptability nozzle-array printing system based on a set covering printing planning model for printed display manufacturing.

Inkjet printing technology is expected to enhance printed display mass production technology in the future. Nozzle-array printheads form the basis for printed display mass production applications. However, jet instability caused by air bubble entrapment and nozzle wettability changes during the printing process is a major challenge in the application of this technology. To adapt to possible nozzle abnormalities, a high-adaptability nozzle-array printing system based on a set covering printing planning (SCPP) model for printed display manufacturing is designed in this study. The study consists of two parts. First, a printing system based on multistep visual inspection and closed-loop feedback is proposed to accurately detect and screen abnormal nozzle positions. Notably, the inkjet printing system can identify nozzles with abnormal ejection characteristics and ensure that the remaining nozzles work accurately and stably. Then, an SCPP model is established for display pixel printing planning by using the remaining normal nozzles on the nozzle-array printhead. This model can output the most efficient printing path and nozzle printing action and can adapt to any pixel pattern, nozzle type, and abnormal nozzle distribution. The system and technology are highly adaptable and scalable for fabricating large-area printed display devices.

Coalescence Dynamics of a Droplet Impacting on a Rectangular Pixel for Inkjet Printing.

A droplet impacting on a rectangular pixel with an offset is prone to cause the liquid to spread out of the pixel and adhere to adjacent pixels in organic light-emitting diode (OLED) inkjet printing. Therefore, the coalescence of a droplet impacting on a rectangular pixel is crucial in understanding the reliable OLED inkjet printing. In this paper, an assumption is established that the rectangular coalescence process is divided into the fusion part and spread part. On this basis, a dynamics model is introduced to analyze the coalescence behavior of a droplet impacting on a rectangular pixel. According to the law of conservation of mass and energy, dynamic equations are developed to obtain the maximum spread length as a function of time. In addition, the volume of the fluid method is used to simulate coalescence dynamics of a droplet impacting on a rectangular pixel by using the software of FLUENT, and the analytical solutions are consistent with the simulation results. Furthermore, the effects of the positioning error and initial velocity on the coalescence dynamics are analyzed. The results show that small initial velocity and positioning error of the droplet are helpful for the reliable OLED inkjet printing.

Positioning Error Limit for the Last Droplet Deposition into a Microcavity in the Manufacture of Printed OLEDs.

In the manufacture of the emissive layer and the encapsulation layer of organic light-emitting diode panels, inkjet printing has the advantages of high material utilization, low cost, flexibility in patterning, and large-area production. Especially for emissive layer printing, the micro-pixel array brings a higher requirement of droplet positioning accuracy and volume of the liquid in a pixel. To achieve a uniform deposit morphology, several droplets are usually needed in the inkjet printing of emissive layers. As the printing process continues, these droplets coalesce, and its equilibrium outcome can be roughly approximated by a section of an ellipsoidal cap under the interaction of the surface tension and gravity. The existence of the "ellipsoidal cap" enlarges the spread, and the maximum allowable out-of-pixel spreading length is decreased because of the "ellipsoidal cap" in the neighboring pixel. In this research, the volume of fluid method is used to study the behavior of the last droplet deposition into the wetted microcavity. The effects of wettability, droplet deposition speed, and initial volume of the liquid in the pixel on the printable region are investigated, and printing parameter spaces that result in successful printing are established.

A host-based two-gene model for the identification of bacterial infection in general clinical settings.

OBJECTIVES: In this study, we aimed to develop a simple gene model to identify bacterial infection, which can be implemented in general clinical settings. METHODS: We used a clinically availablereal-time quantitative polymerase chain reaction platform to conduct focused gene expression assays on clinical blood samples. Samples were collected from 2 tertiary hospitals. RESULTS: We found that the 8 candidate genes for bacterial infection were significantly dysregulated in bacterial infection and displayed good performance in group classification, whereas the 2 genes for viral infection displayed poor performance. A two-gene model (S100A12 and CD177) displayed 93.0% sensitivity and 93.7% specificity in the modeling stage. In the independent validation stage, 87.8% sensitivity and 96.6% specificity were achieved in one set of case-control groups, and 93.6% sensitivity and 97.1% specificity in another set. CONCLUSIONS: We have validated the signature genes for bacterial infection and developed a two-gene model to identify bacterial infection in general clinical settings.

A Protein Corona Adsorbed to a Bacterial Magnetosome Affects Its Cellular Uptake.

PURPOSE: It is well known that when exposed to human blood plasma, nanoparticles are predominantly coated by a layer of proteins, forming a corona that will mediate the subsequent cell interactions. Magnetosomes are protein-rich membrane nanoparticles which are synthesized by magnetic bacteria; these have gained a lot of attention owing to their unique magnetic and biochemical characteristics. Nevertheless, whether bacterial magnetosomes have a corona after interacting with the plasma, and how such a corona affects nanoparticle-cell interactions is yet to be elucidated. The aim of this study was to characterize corona formation around a bacterial magnetosome and to assess the functional consequences. METHODS: Magnetosomes were isolated from the magnetotactic bacteria, M. gryphiswaldense (MSR-1). Size, morphology, and zeta potential were measured by transmission electron microscopy and dynamic light scattering. A quantitative characterization of plasma corona proteins was performed using LC-MS/MS. Protein absorption was further examined by circular dichroism and the effect of the corona on cellular uptake was investigated by microscopy and spectroscopy. RESULTS: Various serum proteins were found to be selectively adsorbed on the surface of the bacterial magnetosomes following plasma exposure, forming a corona. Compared to the pristine magnetosomes, the acquired corona promoted efficient cellular uptake by human vascular endothelial cells. Using a protein-interaction prediction method, we identified cell surface receptors that could potentially associate with abundant corona components. Of these, one abundant corona protein, ApoE, may be responsible for internalization of the magnetosome-corona complex through LDL receptor-mediated internalization. CONCLUSION: Our findings provide clues as to the physiological response to magnetosomes and also reveal the corona composition of this membrane-coated nanomaterial after exposure to blood plasma.

Interaction of gold and silver nanoparticles with human plasma: Analysis of protein corona reveals specific binding patterns.

Determining how nanomaterials interact with plasma will assist in understanding their effects on the biological system. This work presents a systematic study of the protein corona formed from human plasma on 20nm silver and gold nanoparticles with three different surface modifications, including positive and negative surface charges. The results show that all nanoparticles, even those with positive surface modifications, acquire negative charges after interacting with plasma. Approximately 300 proteins are identified on the coronas, while 99 are commonly found on each nanomaterial. The 20 most abundant proteins account for over 80% of the total proteins abundance. Remarkably, the surface charge and core of the nanoparticles, as well as the isoelectric point of the plasma proteins, are found to play significant roles in determining the nanoparticle coronas. Albumin and globulins are present at levels of less than 2% on these nanoparticle coronas. Fibrinogen, which presents in the plasma but not in the serum, preferably binds to negatively charged gold nanoparticles. These observations demonstrate the specific plasma protein binding pattern of silver and gold nanoparticles, as well as the importance of the surface charge and core in determining the protein corona compositions. The potential downstream biological impacts of the corona proteins were also investigated.

Relationship Between the Serum Total Bilirubin and Inflammation in Patients With Psoriasis Vulgaris.

BACKGROUND: Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. OBJECTIVE: To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. METHODS: A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. RESULTS: Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. CONCLUSION: The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response.

Characterization and Genomic Analysis of Quinolone-Resistant Delftia sp. 670 Isolated from a Patient Who Died from Severe Pneumonia.

Antibiotic-resistant opportunistic pathogens have become a serious concern in recent decades, as they are increasingly responsible for hospital-acquired infections. Here, we describe quinolone-resistant Delftia sp. strain 670, isolated from the sputum of a patient who died from severe pulmonary infection. The draft genome sequence of this strain was obtained by whole-genome shotgun sequencing, and was subjected to comparative genome analysis. Genome analysis revealed that one critical mutation (Ser83Ile in gyrA) might play a decisive role in quinolone resistance. The genome of Delftia sp. strain 670 contains both type II and type VI secretion systems, which were predicted to contribute to the virulence of the strain. Phylogenetic analysis, assimilation tests, and comparative genome analysis indicated that strain 670 differed from the four known Delftia species, suggesting this strain could represent a novel species. Although the study could not determine the strain 670 as the pathogen led to mortality, our findings also presented the pathogenic potential of Delftia species, and the increasing severity of antibiotic resistance among emerging opportunistic pathogens. The whole genome sequencing and comparative analysis improved our understanding of genome evolution in the genus Delftia, and provides the foundation for further study on drug resistance and virulence of Delftia strains.

Acute brucellosis with typical hemophagocytic lymphohistiocytosis accompanying elevated tumor markers.

We reported a typical brucellosis, which was diagnosed as hemophagocytic lymphohistiocytosis (HLH). Although some tumor markers (CEA, CYFRA21-1, NSE, CA19-9) in the patient's serum were elevated, carcinomas were excluded by a variety of inspections including bone marrow aspirations, ultrasound examinations, and whole-body PET-CT scans. It was concluded that serum tumor markers are considered medically necessary as a screening test for brucellosis with HLH, however, detailed inspections were needed to make a final diagnosis. Moreover, combination of epidemiology investigations and laboratory inspections were helpful to determine the etiology of HLH and initiate the corresponding treatments.

Characterization of the morphology and genome of an Escherichia coli podovirus.

Escherichia coli is an important opportunistic pathogen. It can cause sepsis and severe infection. The application of lytic bacteriophages to treat infectious diseases is an alternative to antibiotics. A lytic Escherichia coli phage, designated IME-EC2, was isolated from hospital sewage. Transmission electron microscopy revealed that IME-EC2 to be a member of the family Podoviridae. It had a 60-nm head and a 15-nm tail. Here, we present the complete genome sequence of this phage, which consists of 41,510 bp with an overall G+C content of 59.2 %. A total of 60 coding sequences (CDS) were identified, and the phage genome does not contain any tRNA genes. Forty percent of the unknown CDSs are unique to IME-EC2. This phage does not show significant similarity to other phages at the DNA level, which suggests that IME-EC2 could be a novel phage. One of the unique features identified in the IME-EC2 genome was a gene coding for a putative colanic-acid-degrading protein, which could allow the phage to degrade bacterial capsule and biofilms. Another unique feature is that IME-EC2 does not contain a terminase small subunit, which suggests that this phage may have a unique packaging mechanism. The present work provides novel information on phages and shows that this lytic phage or its products could be exploited to destroy bacterial biofilms and pathogenic E. coli.

Betaine homocysteine methyltransferase (BHMT) as a specific and sensitive blood marker for acute liver injury.

We developed a high-performance ELISA assay and measured serum BHMT levels in healthy individuals and patients with acute liver injury (ALI). The detection range of this ELISA assay was from 1.56 to 100 ng/ml. BHMT levels are significantly higher in ALI groups. In the healthy group (n = 244), the median value (interquartile range, IQR 0-56.40) was 1.83 ng/ml. In the ALI group (n = 42), the median value of BHMT was 748.48 ng/ml (IQR, 0-51095.92). ROC curve analysis demonstrated good sensitivity (0.86) and specificity (0.98). In addition, in five ALI cases with time course samples available, BHMT and ALT both followed the "rise and fall" temporal pattern with the disease progression. However, the slopes of BHMT curves were steeper than ALT curves. And in three out of the five cases, BHMT levels peaked 1 day earlier than ALT levels be a sensitive marker with good prognostic value.

Quantitative liver-specific protein fingerprint in blood: a signature for hepatotoxicity.

We discuss here a new approach to detecting hepatotoxicity by employing concentration changes of liver-specific blood proteins during disease progression. These proteins are capable of assessing the behaviors of their cognate liver biological networks for toxicity or disease perturbations. Blood biomarkers are highly desirable diagnostics as blood is easily accessible and baths virtually all organs. Fifteen liver-specific blood proteins were identified as markers of acetaminophen (APAP)-induced hepatotoxicity using three proteomic technologies: label-free antibody microarrays, quantitative immunoblotting, and targeted iTRAQ mass spectrometry. Liver-specific blood proteins produced a toxicity signature of eleven elevated and four attenuated blood protein levels. These blood protein perturbations begin to provide a systems view of key mechanistic features of APAP-induced liver injury relating to glutathione and S-adenosyl-L-methionine (SAMe) depletion, mitochondrial dysfunction, and liver responses to the stress. Two markers, elevated membrane-bound catechol-O-methyltransferase (MB-COMT) and attenuated retinol binding protein 4 (RBP4), report hepatic injury significantly earlier than the current gold standard liver biomarker, alanine transaminase (ALT). These biomarkers were perturbed prior to onset of irreversible liver injury. Ideal markers should be applicable for both rodent model studies and human clinical trials. Five of these mouse liver-specific blood markers had human orthologs that were also found to be responsive to human hepatotoxicity. This panel of liver-specific proteins has the potential to effectively identify the early toxicity onset, the nature and extent of liver injury and report on some of the APAP-perturbed liver networks.

Characterization of Enterococcus faecalis phage IME-EF1 and its endolysin.

Enterococcus faecalis is increasingly becoming an important nosocomial infection opportunistic pathogen. E. faecalis can easily obtain drug resistance, making it difficult to be controlled in clinical settings. Using bacteriophage as an alternative treatment to drug-resistant bacteria has been revitalized recently, especially for fighting drug-resistant bacteria. In this research, an E. faecalis bacteriophage named IME-EF1 was isolated from hospital sewage. Whole genomic sequence analysis demonstrated that the isolated IME-EF1 belong to the Siphoviridae family, and has a linear double-stranded DNA genome consisting of 57,081 nucleotides. The IME-EF1 genome has a 40.04% G+C content and contains 98 putative coding sequences. In addition, IME-EF1 has an isometric head with a width of 35 nm to 60 nm and length of 75 nm to 90 nm, as well as morphology resembling a tadpole. IME-EF1 can adsorb to its host cells within 9 min, with an absorbance rate more than 99% and a latent period time of 25 min. The endolysin of IME-EF1 contains a CHAP domain in its N-terminal and has a wider bactericidal spectrum than its parental bacteriophage, including 2 strains of vancomycin-resistant E. faecalis. When administrated intraperitoneally, one dose of IME-EF1 or its endolysin can reduce bacterial count in the blood and protected the mice from a lethal challenge of E. faecalis, with a survival rate of 60% or 80%, respectively. Although bacteriophage could rescue mice from bacterial challenge, to the best of our knowledge, this study further supports the potential function of bacteriophage in dealing with E. faecalis infection in vivo. The results also indicated that the newly isolated bacteriophage IME-EF1 enriched the arsenal library of lytic E. faecalis bacteriophages and presented another choice for phage therapy in the future.

Complete Genome Sequence of IME13, a Stenotrophomonas maltophilia bacteriophage with large burst size and unique plaque polymorphism.

Stenotrophomonas maltophilia bacteriophage IME13 is a virulent phage with a large burst size, exceeding 3,000, much larger than that of any other stenotrophomonas phage reported before. It showed effective lysis of Stenotrophomonas maltophilia. Additionally, the phage IME13 developed at least three obviously different sizes of plaques when a single plaque was picked out and inoculated on a double-layer Luria broth agar plate with its host. Here we announce its complete genome and describe major findings from its annotation.

Signal peptide and denaturing temperature are critical factors for efficient mammalian expression and immunoblotting of cannabinoid receptors.

Many researchers employed mammalian expression system to artificially express cannabinoid receptors, but immunoblot data that directly prove efficient protein expression can hardly be seen in related research reports. In present study, we demonstrated cannabinoid receptor protein was not able to be properly expressed with routine mammalian expression system. This inefficient expression was rescued by endowing an exogenous signal peptide ahead of cannabinoid receptor peptide. In addition, the artificially synthesized cannabinoid receptor was found to aggregate under routine sample denaturing temperatures (i.e., ≥95°C), forming a large molecular weight band when analyzed by immuno-blotting. Only denaturing temperatures ≤75°C yielded a clear band at the predicted molecular weight. Collectively, we showed that efficient mammalian expression of cannabinoid receptors need a signal peptide sequence, and described the requirement for a low sample denaturing temperature in immuno-blot analysis. These findings provide very useful information for efficient mammalian expression and immuno-blotting of membrane receptors.

Circulating microRNA-122 as a potential biomarker for liver injury.

Liver-specific microRNA-122 (miR-122) is involved in the replication of hepatitis C virus (HCV) and its potential as a target for antiviral intervention was recently assessed. However, the use of circulating miR-122 in the evaluation of liver function has never been reported. In the present study, changes of serum miRNA levels were first evaluated in acute human hepatotoxicity due to paraquat exposure. Serum samples were collected and analyzed using real-time reverse transcription PCR. The results showed a positive correlation between serum miR-122 and alanine aminotransferase, a clinical biomarker for liver function. Furthermore, serum miR-122 was assessed in patients with hepatitis B and hepatocarcinoma, resulting in distinct miR-122 profiles in these two closely related diseases. In addition to miR-122, another small RNA, U6 small nuclear RNA, was downregulated in hepatocarcinoma patients, suggesting its prognostic significance in this disease. Taken together, these lines of evidence indicate that serum miR-122 may provide a biomarker for diverse liver diseases and, more importantly, suggest that a combination of nucleic acid biomarkers may be used as a sensitive and specific index for discriminating closely related diseases.

Rapid genetic characterization of a novel Enterobacteria phage and determination of its host recognizing genes.

We isolated a novel Enterobacteria phage IME08 from hospital sewage, then confirmed it was a double-stranded DNA phage by digesting its genetic material with DNase I, RNase A and several restriction endonucleases respectively. BLAST results of random fragments generated by a random PCR cloning method revealed that it belonged to T4-like virus. We subsequently determined the host recognizing genes (g37 and g38) sequence with a PCR-based "genome jumping" protocol based on highly conserved region at 5' terminus of g37 from four other T4-like Bacteriophages (T4, JS98, T2 and K3). These molecular biological methods enabled us to readily characterize the bacteriophage and efficiently determine the sequence of the genes of interest based on very limited conserved sequence information.