Potent synergy and sustained bactericidal activity of polymyxins combined with Gram-positive only class of antibiotics versus four Gram-negative bacteria.

BACKGROUND: Gram-negative bacteria (GNB) are becoming increasingly resistant to a wide variety of antibiotics. There are currently limited treatments for GNB, and the combination of antibiotics with complementary mechanisms has been reported to be a feasible strategy for treating GNB infection. The inability to cross the GNB outer membrane (OM) is an important reason that a broad spectrum of Gram-positive only class of antibiotics (GPOAs) is lacking. Polymyxins may help GPOAs to permeate by disrupting OM of GNB. OBJECTIVE: To identify what kind of GPOAs can be aided to broaden their anti-GNB spectrum by polymyxins, we systematically investigated the synergy of eight GPOAs in combination with colistin (COL) and polymyxin B (PMB) against GNB in vitro. METHODS: The synergistic effect of COL or PMB and GPOAs combinations against GNB reference strains and clinical isolates were determined by checkerboard tests. The killing kinetics of the combinations were assessed using time-kill assays. RESULTS: In the checkerboard tests, polymyxins-GPOAs combinations exert synergistic effects characterized by species and strain specificity. The synergistic interactions on P. aeruginosa strains are significantly lower than those on strains of A. baumannii, K. pneumoniae and E. coli. Among all the combinations, COL has shown the best synergistic effect in combination with dalbavancin (DAL) or oritavancin (ORI) versus almost all of the strains tested, with FICIs from 0.16 to 0.50 and 0.13 to < 0.28, respectively. In addition, the time-kill assays demonstrated that COL/DAL and COL/ORI had sustained bactericidal activity. CONCLUSIONS: Our results indicated that polymyxins could help GPOAs to permeate the OM of specific GNB, thus showed synergistic effects and bactericidal effects in the in vitro assays. In vivo combination studies should be further conducted to validate the results of this study.

Wearable Bioimpedance-Based Deep Learning Techniques for Live Fish Health Assessment under Waterless and Low-Temperature Conditions.

(1) Background: At present, physiological stress detection technology is a critical means for precisely evaluating the comprehensive health status of live fish. However, the commonly used biochemical tests are invasive and time-consuming and cannot simultaneously monitor and dynamically evaluate multiple stress levels in fish and accurately classify their health levels. The purpose of this study is to deploy wearable bioelectrical impedance analysis (WBIA) sensors on fish skin to construct a deep learning-based stress dynamic evaluation model for precisely estimating their accurate health status. (2) Methods: The correlation of fish (turbot) muscle nutrients and their stress indicators are calculated using grey relation analysis (GRA) for allocating the weight of the stress factors. Next, WBIA features are sieved using the maximum information coefficient (MIC) in stress trend evaluation modeling, which is closely related to the key stress factors. Afterward, a convolutional neural network (CNN) is utilized to obtain the features of the WBIA signals. Then, the long short-term memory (LSTM) method learns the stress trends with residual rectification using bidirectional gated recurrent units (BiGRUs). Furthermore, the Z-shaped fuzzy function can accurately classify the fish health status by the total evaluated stress values. (3) Results: The proposed CNN-LSTM-BiGRU-based stress evaluation model shows superior accuracy compared to the other machine learning models (CNN-LSTM, CNN-GRU, LSTM, GRU, SVR, and BP) based on the MAPE, MAE, and RMSE. Moreover, the fish health classification under waterless and low-temperature conditions is thoroughly verified. High accuracy is proven by the classification validation criterion (accuracy, F1 score, precision, and recall). (4) Conclusions: the proposed health evaluation technology can precisely monitor and track the health status of live fish and provides an effective technical reference for the field of live fish vital sign detection.

rGO-PDMS Flexible Sensors Enabled Survival Decision System for Live Oysters.

The shell-closing strength (SCS) of oysters is the main parameter for physiological activities. The aim of this study was to evaluate the applicability of SCS as an indicator of live oyster health. This study developed a flexible pressure sensor system with polydimethylsiloxane (PDMS) as the substrate and reduced graphene oxide (rGO) as the sensitive layer to monitor SCS in live oysters (rGO-PDMS). In the experiment, oysters of superior, medium and inferior grades were selected as research objects, and the change characteristics of SCS were monitored at 4 °C and 25 °C. At the same time, the time series model was used to predict the survival rate of live oyster on the basis of changes in their SCS characteristics. The survival times of superior, medium and inferior oysters at 4 °C and 25 °C were 31/25/18 days and 12/10/7 days, respectively, and the best prediction accuracies for survival rate were 89.32%/82.17%/79.19%. The results indicate that SCS is a key physiological indicator of oyster survival. The dynamic monitoring of oyster vitality by means of flexible pressure sensors is an important means of improving oyster survival rate. Superior oysters have a higher survival rate in low-temperature environments, and our method can provide effective and reliable survival prediction and management for the oyster industry.

Suppression of the caspase-1/GSDMD-mediated pyroptotic signaling pathway through dexamethasone alleviates corneal alkali injuries.

The pathological mechanism of corneal injuries mediated by alkali burns are associated with Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 protein (NLRP3)-related corneal sterile inflammation. Whether the executive protein gasdermin D (GSDMD) of pyroptosis mediated by the NLRP3 inflammasome is present in alkali-induced corneal lesions remains unclear. Dexamethasone (Dex) is a commonly used drug for ocular surface diseases that can maintain corneal transparency and anti-inflammatory effects by topical administration. Here, we presented evidence that the effect of Dex on the pyroptosis-related caspase-1/GSDMD pathway in corneal alkali burns (CABs). We assessed the clinical manifestations and histological characteristics of the placebo group, 0.05% Dex group, 0.1% Dex group on day 3 or day 7 postburn and the control group (healthy corneas). The expression of factors (including NLRP3, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N termini, pro-interleukin(IL)-1ß, IL-1ß, pro-IL-18 and IL-18) involved in the pyroptosis related caspase-1/GSDMD signaling pathway was demonstrated by molecular experiments in CAB. Alkali burns can upregulate the originally relatively dim expression of NLRP3, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, pro-IL-1ß, pro-IL-18, IL-1ß and IL-18 in the healthy corneal epithelium and stroma. However, Dex can reverse the enhanced expression at the two timepoints. Corneal sterile inflammation can activate the NLRP3 inflammasome through the innate immune response mechanism and then activate the pyroptosis-related caspase-1/GSDMD signaling pathway. In addition, Dex can inhibit pyroptosis through this pathway.

A self-designed versatile and portable sensing device based on smart phone for colorimetric detection.

A UV-vis spectrometer, as a sort of important analytical instrument, has been widely used to analyze various substances. However, expensive equipment and skilled operators are required, which limits its broad applications for out-of-lab and daily measurements. In this work, a self-designed sensing device based on smart phone was developed as a sensitive, cost-effective, facile, and portable testing tool. The sensing device fabricated by 3D printing was used to lodge a sample solution and produce a light signal, and the optical sensor on a smart phone worked as a transducer. The light source in the device generated wide-wavelength radiation, which passed through an inner filter and only light of a designated wavelength reached the testing solution. The intensity of transmitted light was then measured by an optical sensor internally installed in most smart phones, where the signals were processed as well. The feasibility of our device was verified by detecting four kinds of common heavy metal ions in actual water samples, and the testing results showed good agreement with those obtained from the UV-vis spectrometer. This work is expected to shed some light on the construction of smart phone-based sensors, featuring decent portability, simple operation, low cost, high sensitivity, and good accuracy.

Extraction and bioinformatics analysis of Chlamydia trachomatis LpxA.

OBJECTIVE: The aim of this study is to clone the LpxA gene of Chlamydia trachomatis and analyze its biological characteristics. METHODS: Specific primers were designed according to the sequence of Ct LpxA gene. LpxA gene was amplified by PCR and connected to pMD18-T vectors. Positive clones were selected for PCR and DNA sequencing. Finally, bioinformatics software was used to analyze the biological properties of LpxA protein. RESULTS: The total length of LpxA gene was 840 bp, encoding 280 amino acids. LpxA protein has no signal peptide and was located in bacterial cytoplasm. The prediction of secondary structure showed that the α-helix, extended strand, ß-turn and random coil accounted for 19.6%, 32.8%, 11.4% and 36%, respectively. According to the prediction of tertiary structure, three identical LpxA molecules constituted homologous trimers. It was predicted that there were 11 B cell epitopes in LpxA. CONCLUSION: Ct Lpxa gene was cloned, and LpxA protein structure and function were predicted.

Facile microfluidic fabrication of monodispersed self-coupling microcavity with fine tunability.

Whispering gallery mode (WGM) resonators have received extensive attention because of their nonlinear optical application in lasers and sensors. Optical microcavities are excellent candidates for constructing powerful microlasers and label-free biosensors, owing to their low optical losses and small size. However, most of these microcavity syntheses rely on sophisticated fabrication methods and cannot be manipulated easily. To achieve facile and versatile microcavity fabrication, we present a robust microfluidics method for monodispersed self-coupling optical microcavity fabrication with a fine tunability. The microcavity polydispersity was less than 3%. The optical microcavity size could be varied from 10 to 30 µm with a steady quality factor (Q) of approximately 1000. The lowest laser threshold that we obtained was 0.82 µJ with a microcavity size of 20 µm. The doped fluorescent dye concentration can be tuned precisely from 0.001 to 0.05 wt% to explore an optimized fluorescent background. The experimental results and theoretical simulation match well in terms of Q and the electrometric resonance field intensity. Compared with previous precise and practical fabrication methods, we have demonstrated a facile approach for versatile optical microcavity fabrication. This method can vary the microcavity materials, size, doped fluorescent dye concentration, WGM resonance spectrum, Q factor, and laser threshold easily to adapt to various circumstances and specific applications.

Multi-layer silver nanowire/polyethylene terephthalate mesh structure for highly efficient transparent electromagnetic interference shielding.

Electromagnetic interference protection in optoelectronic devices is challenging because of the dual requirements of optical transmittance and high shielding effectiveness (SE). Herein, we propose a novel silver nanowire (AgNW)/polyethylene terephthalate (PET) multi-layer mesh pattern structure for transparent electromagnetic shielding obtained via laser marking and transfer printing. A three-layer composite shielding film with an optical transmittance of 67.8% exhibits a SE of 44 dB at 10 GHz, which is superior to most of the reported transparent shielding films composed of AgNWs to date. The newly designed multi-layer composite structure can enhance the transparent shielding properties of the shielding film via optimization of the AgNW distribution and the shielding film structure. It is expected that this multi-layer mesh composite structure will have splendid application prospects in electromagnetic shielding films, which require both light transmittance and high SE.

Electrochemical sensor based on dual-template molecularly imprinted polymer and nanoporous gold leaf modified electrode for simultaneous determination of dopamine and uric acid.

A novel electrochemical sensor based on dual-template molecularly imprinted polymer (MIP) with nanoporous gold leaf (NPGL) was established for the simultaneous determination of dopamine (DA) and uric acid (UA). NPGL acts as an enlarged loading platform to enhance sensing capacity, and the MIP layer was synthesized in situ in the presence of monomer and dual templates (DA and UA) to provide specific recognition. Under the optimal conditions, the sensor shows a good linear range of 2.0~180 µM for DA at a working potential of 0.15 V (vs. Ag/AgCl) and 5.0~160 µM for UA at 0.35 V (vs. Ag/AgCl), with the respective detection limit of 0.3 µM and 0.4 µM (S/N = 3). Good selectivity of the sensor to its dual templates was confirmed as the sensing signals are significantly different between templates and interfering species. The responses maintained higher than 96% of the initial values after 30-day storage, and the day-to-day relative standard deviation is less than 3.0%. Real sample simultaneous determination of DA and UA was conducted with bovine serum, and the results were in good agreement with those from high-performance liquid chromatography. It can be concluded that this work offers a reliable, facile, fast, and cost-effective method of simultaneous quantification of two or more chem-/bio-molecules. Graphical abstract.

An electrochemical sensor based on MOF-derived NiO@ZnO hollow microspheres for isoniazid determination.

The electrocatalytic activity of metal-organic framework (MOF)-derived NiO@ZnO hollow microspheres was studied for its application to an isoniazid sensor. The MOF-derived NiO@ZnO hollow spheres were synthesized by the coordination reaction of terephthalic acid with Zn2+ and Ni2+ and followed by calcination. Morphology characterization showed that the MOF-derived NiO@ZnO sphere has circular core-shell structure with pores on its surface. Further electrochemical characterization of the prepared sensor by cyclic voltammetry and differential pulse voltammetry proved that the material has good electrical conductivity and strong catalytic ability. Distinct oxidation peaks occur for INZ at potential of 0.22 V (vs. saturated calomel electrode). Under the optimal experimental conditions, the linear range of the sensor for isoniazid determination was 0.8 ~ 800 µM, and the detection limit was 0.25 µM (S/N = 3). In addition, the sensor displayed good stability, repeatability, and reproducibility. The established method was successfully applied for determination of isoniazid in tablets and mouse serum with admirable accuracy and reliability. Graphical abstract Schematic presentation of an electrochemical sensor based on MOF-derived NiO@ZnO hollow microspheres for isoniazid determination.

Curcumin suppressed proliferation and migration of human retinoblastoma cells through modulating NF-κB pathway.

PURPOSE: To study the effect of curcumin on proliferation and invasion of the human retinoblastoma cells and its potential mechanism. METHODS: A cell line of retinoblastoma (WERI-Rb-1) was treated with various concentrations of curcumin (0-40 µM). Cell number was counted with CCK8 kit, and cell migration was assessed using the Transwell assay. Immunoblotting was performed to detect the proteins of metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) as well as nuclear translocation of nuclear factor-κB (NF-κB, p65). RESULTS: Proliferation and migration of WERI-Rb-1 cells were significantly inhibited by curcumin in a concentration-dependent manner (0-40 µM). Protein expressions of MMP-2, MMP-9 and VEGF in the WERI-Rb-1 cells were also significantly inhibited by curcumin in a concentration-dependent manner (0-40 µM). Furthermore, nuclear translocation of NF-κB (p65) was significantly inhibited by curcumin in time-dependent manner (6-24 h). CONCLUSION: Curcumin inhibited proliferation and migration of WERI-Rb-1 cells, a cell line of human retinoblastoma, which might be through modulating NF-κB and its downstream proteins including VEGF, MMP-2, and MMP-9.

Droplet-based microfluidics systems in biomedical applications.

Microfluidics has made a very impressive progress in the past decades due to its unique and instinctive advantages. Droplet-based microfluidic systems show excellent compatibility with many chemical and biological reagents and are capable of performing variety of operations that can implement microreactor, complex multiple core-shell structure, and many applications in biomedical research such as drug encapsulation, targeted drug delivery systems, and multifunctionalization on carriers. Droplet-based systems have been directly used to synthesize particles and encapsulate many biological entities for biomedicine applications due to their powerful encapsulation capability and facile versatility. In this paper, we review its origin, deviation, and evolution to draw a clear future, especially for droplet-based biomedical applications. This paper will focus on droplet generation, variations and complication as starter, and logistically lead to the numerous typical applications in biomedical research. Finally, we will summarize both its challenge and future prospects relevant to its droplet-based biomedical applications.

Nano oxide intermediate layer assisted room temperature sintering of ink-jet printed silver nanoparticles pattern.

Sintering of metallic nanoparticles (NPs) at low temperature is highly wanted in the manufacturing of flexible electronics. And for ink-jet printing, the metallic NPs after printing usually need thermal or chemical post-treatment to remove stabilizing agents and achieve conductivity. Here, we reported a facile method to realize one-step printed sintering of silver nanoparticle (AgNP) ink at room temperature by using intermediate coated layers composed of oxide NPs and polyvinyl alcohol (PVA) mixture. We found that the detachment of the stabilizer (citrate) from the AgNPs was caused by hydroxyl groups on the surface of the oxide NPs, which enabled the coalescence and sintering of the AgNPs. With the aid of SiO2 NPs based intermediate layer, the patterns showed resistivity as low as 3.45 µΩ cm after sintering. Moreover, the mixed PVA could ensure the forming quality of patterns owing to its adsorption of ink and the high adhesiveness of PVA with substrates. So, we envision that this approach could serve as an adaptive method for sintering of AgNPs based conductive patterns on various substrates at room temperature and promote the manufacture of printed electronics.

Highly stretchable patternable conductive circuits and wearable strain sensors based on polydimethylsiloxane and silver nanoparticles.

Patterned circuits on highly stretchable conductive films are critical in the practical application of next-generation flexible and wearable devices. Currently, most patterned circuits do not exhibit highly stretchable properties, and a lithography process in vacuum is required. In this study, silver nanoparticles (AgNPs) and liquid polydimethylsiloxane (PDMS) are mixed together to form liquid conductive adhesives (CAs). Various stretchable patterned circuits are prepared using this CA to achieve all required functions. Six basic patterns, including rhombus, straight lines, serpentine, triangle, ellipses, and fold line, are studied for their stretchable and electrical properties. The film is found to maintain excellent conductivity after withstanding tensile strain of up to 320% and more than 10 000 stretching-releasing cycles of 0%-150%. More than 86% of visible lights can be penetrated through the film due to the transparent substrates. Functional and wearable devices are manufactured, and devices fabricated from rhombus-pattern circuits are found to exhibit stable electrical conductivity when subjected to very high tensile strains. According to the sensitivity of the straight-line patterned circuit to strain, a repeatable use sensitive strain sensor is studied. Also, two types of artificial electrical skin are demonstrated.

Tuberculosis of acromioclavicular joint: a case report.

BACKGROUND: Osteoarticular tuberculosis is a great masquerader presenting in varied forms and in atypical locations, and it is prone to misdiagnosis and missed diagnosis. Isolated acromioclavicular joint tuberculosis has been reported rarely. CASE PRESENTATION: A 19-year-old man presented with a chronic, mild pain, non-healing ulcer in right shoulder. Imaging of the shoulder revealed destruction of the acromioclavicular joint and histopathology confirmed the diagnosis of acromioclavicular tuberculosis. The patient underwent debridement, synovectomy and drainage of the abscess and recovered well with antitubercular therapy postoperatively. CONCLUSIONS: Awareness of this uncommon presentation of osteoarticular tuberculosis may assist in earlier diagnosis. Especially, in endemic countries, osteoarticular tuberculosis should be considered as a differential diagnosis in all atypical presentations to avoid residual problems.

Electrochemical microfluidics techniques for heavy metal ion detection.

Heavy metals refer to metals with a density above 5 × 103 kg m-3, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg). Even a trace amount of heavy metals is detrimental to human health. With the increasing significance of detection of heavy metals, the use of the electrochemical detection technique combined with microfluidics is a promising strategy and has thus attracted wide attention from academia and is the subject of this review. First, this review introduces the basics of electrochemical detection and microfluidics. Second, this review presents and evaluates a variety of electrochemical microfluidics technologies for heavy metal ions detection that are user friendly, portable, inexpensive, and easy to manufacture compared to traditional methods. The categorization is based on different detected ions in the order of Pb, Cd, As, Hg, Mn, and Zn. Finally, the author summarizes the development of detection technology in recent years and puts forward a perspective for the future prospects.

Correction: Electrochemical microfluidics techniques for heavy metal ion detection.

Correction for 'Electrochemical microfluidics techniques for heavy metal ion detection' by Su Li et al., Analyst, 2018, 143, 4230-4246.

Conductivity enhancement of silver nanowire networks via simple electrolyte solution treatment and solvent washing.

As a promising replacement material for indium tin oxide in flexible electronics, silver nanowires (AgNWs) usually need complicated post-treatment to reduce the high contact resistance across the intersections when used as transparent conductive films. In this work, a widely applicable nano-joining method for improving the overall conductivity of AgNW networks with different kinds of electrolyte solutions is presented. By treatment with an electrolyte solution with appropriate ionic strengths, the insulating surfactant layer (polyvinylpyrrolidone, PVP) on the AgNWs could be desorbed, and the AgNW network could be densified. The sheet resistance of the AgNW film on a glass slide is reduced by 60.9% (from 67.5 to 26.4 Ohm sq-1) with a transmittance of 92.5%. High-resolution transmission electron microscopy analysis indicates that atomic diffusion occurs at the intersection of two AgNWs. Thus, metallurgical bonding on the nanometer scale is achieved across the junctions of the AgNWs, leading to a significant enhancement in the conductivity of the AgNW network.

Controlling the Hierarchical Assembly of π-Conjugated Oligoelectrolytes.

Here, a means of controlling the assembly pathways of p-conjugated oligoelectrolytes into supramolecular fibers and microtubes is presented, and it is shown how the addition of small end-caps to well-defined and pH-responsive conjugated oligomers can alter the balance between repulsive and attractive supramolecular forces and enables control of the morphology of the hierarchical assembly process. The assembly stages from nuclei to protofibers are evidenced and a hypothesis on the mechanism of microtubes formation using a combination of analytical methods is provided, revealing different degrees of order at different scales along the structural hierarchy.

Photocatalytically Powered Matchlike Nanomotor for Light-Guided Active SERS Sensing.

Surface enhanced Raman spectroscopy (SERS) is a powerful optical sensing technique that can detect analytes of extremely low concentrations. However, the presence of enough SERS probes in the detection area and a close contact between analytes and SERS probes are critical for efficient acquisition of a SERS signal. Presented here is a light-powered micro/nanomotor (MNM) that can serve as an active SERS probe. The matchlike AgNW@SiO2 core-shell structure of the nanomotors work as SERS probes based on the shell-isolated enhanced Raman mechanism. The AgCl tail serves as photocatalytic nanoengine, providing a self-propulsion force by light-induced self-diffusiophoresis. The phototactic behavior was utilized to achieve enrichment of the nanomotor-based SERS probes for on-demand biochemical sensing. The results demonstrate the possibility of using photocatalytic nanomotors as active SERS probes for remote, light-controlled, and smart biochemical sensing on the micro/nanoscale.