On-chip flow cytometer using integrated photonics for the detection of human leukocytes.

Differentiation between leukocyte subtypes like monocytes and lymphocytes is essential for cell therapy and research applications. To guarantee the cost-effective delivery of functional cells in cell therapies, billions of cells must be processed in a limited time. Yet, the sorting rates of commercial cell sorters are not high enough to reach the required yield. Process parallelization by using multiple instruments increases variability and production cost. A compact solution with higher throughput can be provided by multichannel flow cytometers combining fluidics and optics on-chip. In this work, we present a micro-flow cytometer with monolithically integrated photonics and fluidics and demonstrate that both the illumination of cells, as well as the collection of scattered light, can be realized using photonic integrated circuits. Our device is the first with sufficient resolution for the discrimination of lymphocytes and monocytes. Innovations in microfabrication have enabled complete integration of miniaturized photonic components and fluidics in a CMOS-compatible wafer stack. In combination with external optics, the device is ready for the collection of fluorescence using the on-chip excitation.

Photocatalytic removal of organophosphorus pesticide by the WO3-Fe3O4/rGO photocatalyst under visible light.

The WO3-Fe3O4/reduced graphene oxide (rGO) composite was synthesized with a hydrothermal method for the photocatalytic removal of diazinon (DZ) in visible light. The influence of catalyst concentration (0.5-1.5 g L-1), pH (5-9), and initial pollutant value (5-15 mg L-1) on the pesticide degradation was studied. The performance of the WO3-Fe3O4/rGO nanocomposite for DZ degradation under visible light shows 94% degradation of 5 mg L-1 DZ for 100 min with 1 g L-1 nanocomposite, and the degradation kinetic was modeled in pseudo-first order (PFO) and the maximum kobs was 0.0248 min-1. The photocatalytic mechanism and the intermediates of DZ degradation were identified. In addition, the WO3-Fe3O4/rGO catalyst showed reusability after 4 runs. The results of this work illustrate that the WO3-Fe3O4/rGO nanocomposite can be applied for real use owing to its high catalytic performance.

Composition-Dependent Cytotoxic and Antibacterial Activity of Biopolymer-Capped Ag/Au Bimetallic Nanoparticles against Melanoma and Multidrug-Resistant Pathogens.

Nanostructured silver (Ag) and gold (Au) are widely known to be potent biocidal and cytotoxic agents as well as biocompatible nanomaterials. It has been recently reported that combining both metals in a specific chemical composition causes a significant enhancement in their antibacterial activity against antibiotic-resistant bacterial strains, as well as in their anticancer effects, while preserving cytocompatibility properties. In this work, Ag/Au bimetallic nanoparticles over a complete atomic chemical composition range were prepared at 10 at% through a green, highly reproducible, and simple approach using starch as a unique reducing and capping agent. The noble metal nanosystems were thoroughly characterized by different analytical techniques, including UV-visible and FT-IR spectroscopies, XRD, TEM/EDS, XPS and ICP-MS. Moreover, absorption spectra simulations for representative colloidal Ag/Au-NP samples were conducted using FDTD modelling. The antibacterial properties of the bimetallic nanoparticles were determined against multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, showing a clear dose-dependent inhibition even at the lowest concentration tested (5 µg/mL). Cytocompatibility assays showed a medium range of toxicity at low and intermediate concentrations (5 and 10 µg/mL), while triggering an anticancer behavior, even at the lowest concentration tested, in a process involving reactive oxygen species production per the nanoparticle Au:Ag ratio. In this manner, this study provides promising evidence that the presently fabricated Ag/Au-NPs should be further studied for a wide range of antibacterial and anticancer applications.

Molecular Epidemiology and Drug Resistance Pattern of Carbapenem-Resistant Klebsiella pneumoniae Isolates from Iran.

The emergence and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates and their involvement in several nosocomial outbreaks are of high concern. This study was conducted to investigate the genetic relatedness and molecular determinants of carbapenem resistance in 100 CRKP isolates. Susceptibility to carbapenems as well as other antibiotics was determined by using disk diffusion method. The Modified Hodge test was performed for detection of carbapenemase production. The minimum inhibitory concentrations of selected antibiotics were determined by broth microdilution method. The presence of blaOXA-48, blaKPC, blaNDM, and blaVIM carbapenemase genes was examined by PCR, and clonal relatedness of CRKP isolates was investigated by pulsed-field gel electrophoresis (PFGE) analysis. blaOXA-48 was the most frequent carbapenemase gene (72%), followed by blaNDM (31%). None of the isolates harbored blaKPC and blaVIM genes. PFGE separated the majority of isolates into 10 clusters, including the major clusters A and B, carrying blaOXA-48, and clusters C and D, carrying blaNDM, and 4 isolates had a unique PFGE pattern. An increased rate of colistin resistance (50%) was detected among the isolates. Tigecycline was found to be the most active agent against CRKP isolates. Our results revealed that high prevalence of blaOXA-48 and blaNDM carbapenamses and resistance to colistin are alarming threats, necessitating an immediate action to prevent the spread of carbapenem-colistin-resistant K. pneumoniae isolates in Iran.

Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors.

OBJECTIVES: 15-Lipoxygenases are one of the iron-containing proteins capable of performing peroxidation of unsaturated fatty acids in animals and plants. The critical role of enzymes in the formation of inflammations, sensitivities, and some cancers has been demonstrated in mammals. The importance of enzymes has led to the development of mechanistic studies, product analysis, and synthesis of inhibitors. MATERIALS AND METHODS: The inhibitory activity of all synthetic compounds against SLO (soybean 15-lipoxygenase: L1; EC 1,13,11,12) was determined using the peroxide formation method. In this method, the basis of evaluation of lipoxygenase activity is measuring the concentration of fatty acid peroxide. All measurements were compared with 4-​methyl-​2-​(4-​methylpiperazinyl)pyrimido[4,​5-​b]benzothiazine (4-MMPB) as one of the known lipoxygenase inhibitors. The radical scavenging ability of all synthetic compounds using stable free radicals (DPPH: 2,2-diphenyl-1-picrylhydrazyl) was measured for further investigation. RESULTS: In this study, a series of esters from phenolic acids with terpenoid alcohols was synthesized and their inhibitory potency against soybean 15-lipoxygenase and their free radical scavenging properties were determined. Among the synthetic compounds, adamantyl protocatetuate 2j and bornyl protocatetuate 2o showed the most potent inhibitory activity with IC50 values of 0.95 and 0.78 µm, respectively. CONCLUSION: By changing the alcohol and acyl portions of stylosin, it was found that electronic properties play main role in lipoxygenase inhibition potency in contrast with steric features. Insertion of more reductive phenolic moiety such as catechuate and gallate lead to more lipoxygenase inhibition potency of the esters as observed in their radical scavenging activity.

Compact fabrication-tolerant subwavelength-grating-based two-mode division (de)multiplexer.

Regarding the importance of bandwidth and capacity expansion in communication systems, a novel mode division (de)multiplexer based on subwavelength grating (SWG) is proposed. SWG-based devices could have smaller sizes, be much more fabrication-tolerant, and have much wider bandwidths due to the reduced confinement of the field and dispersion. It is also feasible to reduce the loss of a SWG-based device by tuning the duty cycle of the grating. Owing to these properties of SWGs, we have designed a compact fabrication-tolerant two-mode division (de)multiplexer. A flat-top transmission of >0.89 (loss <0.5 dB) is obtained over 65 nm from 1500 to 1565 nm, completely covering the entire C-band used for dense wavelength division multiplexing. Moreover, the cross-talk is <-10 dB for a broad bandwidth of ∼120 nm over which the loss of the complete device including both multiplexer and demultiplexer is <1 dB. Therefore, the proposed device is promising for high-capacity optical communications in both conventional and entirely SWG-based silicon photonic circuits.

MgrB Alterations Mediate Colistin Resistance in Klebsiella pneumoniae Isolates from Iran.

Colistin is one of the last-resort therapeutic agents to combat multidrug-resistant Gram-negative bacteria (GNB) including Klebsiella pneumoniae. Although it happens rarely, resistance to colistin has been reported for several GNB. A total of 20 colistin resistant (col-R) and three colistin susceptible (col-S) clinical isolates of K. pneumoniae were studied to explore the underlying mechanisms of colistin resistance. The presence of plasmid encoded resistance genes, mcr-1, mcr-2, mcr-3, and mcr-4 genes were examined by PCR. The nucleotide sequences of pmrA, pmrB, phoP, phoQ, and mgrB genes were determined. To evaluate the association between colistin resistance and upregulation of pmrHFIJKLM and pmrCAB operons, transcriptional level of the pmrK and pmrC genes encoding for lipopolysaccharide target modifying enzymes was quantified by RT-qPCR analysis. None of the plasmid encoded resistance genes were detected in the studied isolates. Inactivation of MgrB due to nonsense mutations and insertion of IS elements was observed in 15 col-R isolates (75%). IS elements (IS5-like and IS1-like families) most commonly targeted the coding region and in one case the promoter region of the mgrB. Complementation with wild-type MgrB restored colistin susceptibility in isolates with altered mgrB. All col-R isolates lacked any genetic alterations in the pmrA, phoP, and phoQ genes and substitutions identified in the pmrB were not found to be involved in resistance conferring determined by complementation assay. Colistin resistance linked with upregulation of pmrHFIJKLM and pmrCAB operons with the pmrK and pmrC being overexpressed in 20 and 11 col-R isolates, respectively. Our results demonstrated that MgrB alterations are the major mechanisms contributing to colistin resistance in the tested K. pneumoniae isolates from Iran.

Fabrication-friendly subwavelength-structure-assisted waveguide for dispersion engineering.

A subwavelength structure deposited on top of a silicon strip is utilized as a novel tool for dispersion engineering. The equivalent refractive index of the subwavelength structure can be tailored through adjusting its period and duty cycle. As finding suitable materials with both appropriate refractive index and fabrication compatibility is one of the main difficulties in dispersion engineering, the possibility of refractive index engineering is the most significant advantage of the proposed waveguide. It can be beneficial for controlling the properties of the fundamental quasi-TM mode and consequently its dispersion characteristics without any concern about material compatibility. Utilizing this waveguide geometry, a wide and flattened low-dispersion bandwidth can be achieved. Moreover, high anomalous and normal dispersion is realizable without any degradation in dispersion flatness over bandwidth. Therefore, the proposed waveguide structure is promising for dispersion tailoring in both linear and nonlinear applications.

Bilayer dispersion-flattened waveguides with four zero-dispersion wavelengths.

We propose a new type of bilayer dispersion-flattened waveguides that have four zero-dispersion wavelengths. Low and flat dispersion can be achieved by using two different material combinations, with a much smaller index contrast as compared to the previously proposed slot-assisted dispersion-flattened waveguides. Without using a nano-slot, dispersion becomes less sensitive to waveguide dimensions, which is highly desirable for high-yield device fabrication. Ultra-low dispersion, high nonlinearity, and fabrication-friendly design would make it promising for practical implementation of nonlinear photonic functions. The proposed waveguide configuration deepens our understanding of the dispersion flattening principle.

Strip/slot hybrid arsenic tri-sulfide waveguide with ultra-flat and low dispersion profile over an ultra-wide bandwidth.

A strip/slot hybrid arsenic tri-sulfide waveguide with a horizontal silicon dioxide slot is proposed. The waveguide exhibits an ultra-flat and low dispersion profile with four zero-dispersion wavelengths. Tuning structural parameters of the waveguide causes tailoring the dispersion. There is only a low dispersion of approximately ± 3 ps/(nm · km) over a 1035 nm bandwidth. It is shown that the waveguide has less sensitivity to the variations of the structural parameters and fabrication errors compared to silicon waveguides. Moreover, nonlinear coefficient, figure of merit, third-order dispersion and phase-matching condition in four-wave mixing are studied. This waveguide has a great potential for nonlinear applications in a wide range of wavelengths.

Synthesis and SAR comparative studies of 2-allyl-4-methoxy-1-alkoxybenzenes as 15-lipoxygenase inhibitors.

A group of 2-alkoxy-5-methoxyallylbenzene were designed, synthesised and evaluated as potential inhibitors of the soybean 15-lipoxygenase (SLO) on the basis of the eugenol and esteragol structures. Compound 4d showed the best half maximal inhibitory concentration (IC50) for SLO inhibition (IC50 = 5.9 ± 0.6 µM). All the compounds were docked in the SLO active site retrieved from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB entry: 1IK3) and showed that the allyl group of the synthetic compounds similar to the linoleic acid double bond, were oriented toward the Fe³+-OH moiety in the active site of the enzyme and this conformation was especially fixed by the hydrophobic interaction of the 2-alkoxy group with Leu5¹5, Trp5¹9, Val566 and Ile57². It was concluded that the molecular volume and shape of the alkoxy moiety was a major factor in the inhibitory potency variation of the synthetic compounds.

Effect of chlorhexidine on coronal microleakage from root canals obturated with Resilon/Epiphany Self-Etch.

This ex vivo study compared saliva coronal microleakage in root canals filled with Resilon/Epiphany Self-Etch (SE) system after final irrigation with different solutions. A total of 60 extracted single-rooted human teeth were instrumented using Mtwo Ni-Ti rotary instruments and divided into two experimental groups (n = 20 each) and positive and negative control groups (n = 10 each). The canals were irrigated with 1.3% NaOCl during instrumentation. After removing the smear layer with 17% EDTA, the root canals in groups A and B were flushed with distilled water and 2% chlorhexidine (CHX), respectively, after which they were obturated with Resilon/Epiphany SE using lateral compaction technique. After sterilizing the whole system with gamma-rays, saliva leakage was tested using a split-chamber model. Specimens were monitored every 24 h for 60 days. The data collected were then analyzed using the chi-square test and Kaplan-Meier survival analysis. As compared with group A, the specimens in group B tended to be more resistant to saliva leakage; however, the difference was not significant (P > 0.05). In conclusion, our findings suggest that 2% CHX is a good conditioner for root canal dentin before use of Resilon/Epiphany SE.

Design and synthesis of 4-methoxyphenylacetic acid esters as 15-lipoxygenase inhibitors and SAR comparative studies of them.

A group of 4-methoxyphenylacetic acid esters were designed, synthesized and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO) on the basis of eugenol and esteragol structures. Compounds 7d-e showed the best IC(50) in SLO inhibition (IC(50)=3.8 and 1.9 microM, respectively). All compounds were docked in SLO active site and showed that carbonyl group of compounds is oriented toward the Fe(III)-OH moiety in the active site of enzyme and fixed by hydrogen bonding with hydroxyl group. It is assumed that lipophilic interaction of ligand-enzyme would be in charge of inhibiting the enzyme activity. The selectivity of the synthetic esters in inhibiting of 15-HLOb was also compared with 15-HLOa by molecular modeling and multiple alignment techniques.

Design, synthesis and SAR studies of 4-allyoxyaniline amides as potent 15-lipoxygensae inhibitors.

A group of 4-allyloxyaniline amides 5a-o were designed, synthesized and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO) on the basis of eugenol and esteragol structures. Compound 5e showed the best IC(50) in SLO inhibition (IC(50)=0.67+/-0.06 microM). All compounds were docked in SLO active site retrieved from RCSB Protein Data Bank (PDB entry: 1IK3) and showed that allyloxy group of compounds is oriented towards the Fe(3+)-OH moiety in the active site of enzyme and fixed by hydrogen bonding with two conserved His(513) and Gln(716). It is resulted that molecular volume of the amide moiety would be a major factor in inhibitory potency variation of the synthetic amides, where the hydrogen bonding of the amide group could also involve in the activity of the inhibitors.