Search

NLP7 (NIN-LIKE-PROTEIN 7) is the major transcriptional factor responsible for the primary nitrate response (PNR), but the role of its homolog, NLP6, in nitrogen signaling and the interplay between NLP6 and NLP7 remain to be elucidated. In this study, we show that, like NLP7, nuclear localization of NLP6 via a nuclear retention mechanism is nitrate dependent, but nucleocytosolic shuttling of both NLP6 and NLP7 is independent of each other. Compared with single mutants, the nlp6nlp7 double mutant displays a synergistic growth retardation phenotype in response to nitrate. The transcriptome analysis of the PNR showed that NLP6 and NLP7 govern ∼50% of nitrate-induced genes, with cluster analysis highlighting 2 distinct patterns. In the A1 cluster, NLP7 plays the major role, whereas in the A2 cluster, NLP6 and NLP7 are partially functionally redundant. Interestingly, comparing the growth phenotype and PNR under high- and low-nitrate conditions demonstrated that NLP6 and NLP7 exert a more dominant role in the response to high nitrate. Apart from nitrate signaling, NLP6 and NLP7 also participated in high ammonium conditions. Growth phenotypes and transcriptome data revealed that NLP6 and NLP7 are completely functionally redundant and may act as repressors in response to ammonium. Other NLP family members also participated in the PNR, with NLP2 and NLP7 acting as broader regulators and NLP4, -5, -6, and -8 regulating PNR in a gene-dependent manner. Thus, our findings indicate that multiple modes of interplay exist between NLP6 and NLP7 that differ depending on nitrogen sources and gene clusters.

Surface engineering of triboelectric nanogenerator for room temperature self-powered formaldehyde (FA) sensor is demonstrated. Such device delivers not only high power density but also remarkable selectivity and ultra-fast response time to FA gas.

With the rapid growth of emerging point-of-use (POU)/point-of-care (POC) detection technologies, miniaturized sensors for the real-time detection of gases and airborne pathogens have become essential to fight pollution, emerging contaminants, and pandemics. However, the low-cost development of miniaturized gas sensors without compromising selectivity, sensitivity, and response time remains challenging. Microfluidics is a promising technology that has been exploited for decades to overcome such limitations, making it an excellent candidate for POU/POC. However, microfluidic-based gas sensors remain a nascent field. In this review, the evolution of microfluidic gas sensors from basic electronic techniques to more advanced optical techniques such as surface-enhanced Raman spectroscopy to detect analytes is documented in detail. This paper focuses on the various detection methodologies used in microfluidic-based devices for detecting gases and airborne pathogens. Non-continuous microfluidic devices such as bubble/droplet-based microfluidics technology that have been employed to detect gases and airborne pathogens are also discussed. The selectivity, sensitivity, advantages/disadvantages vis-a-vis response time, and fabrication costs for all the microfluidic sensors are tabulated. The microfluidic sensors are grouped based on the target moiety, such as air pollutants such as carbon monoxide and nitrogen oxides, and airborne pathogens such as E. coli and SARS-CoV-2. The possible application scenarios for the various microfluidic devices are critically examined.

Intravenous adipose mesenchymal stem cells (ADSCs) attenuate renal ischemia/reperfusion (IR) injury but with major drawbacks, including the lack of a specific homing effect after systemic infusion, cell trapping in the lung, and early cell death in the damaged microenvironment. We examined whether intrarenal arterial transplantation of dexmedetomidine (DEX) preconditioning ADSC-derived microvesicles (DEX-MVs) could promote further therapeutic potential to reduce renal IR injury. We evaluated the effect of DEX-MVs on NRK-52E cells migration, hypoxia/reoxygenation (H/R)-induced cell death, and reactive oxygen species (ROS) amount and renal IR model in rats. IR was established by bilateral 45 min ischemia followed by 4 h reperfusion. Intrarenal MVs or DEX-MVs were administered prior to ischemia. Renal oxidative stress, hemodynamics and function, western blot, immunohistochemistry, and tubular injury scores were determined. The miR-122-5p expression in kidneys was analyzed using microarrays and quantitative RT-PCR and its action target was predicted by TargetScan. DEX-MVs were more efficient than MVs to increase migration capability and to further decrease H/R-induced cell death and ROS level in NRK-52E cells. Consistently, DEX-MVs were better than MV in increasing CD44 expression, improving IR-depressed renal hemodynamics and renal erythropoietin expression, inhibiting IR-enhanced renal ROS level, tubular injury score, miR-122-5p expression, pNF-κB expression, Bax/caspase 3/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis, blood urea nitrogen, and creatinine levels. The use of NRK-52E cells confirmed that miR-122-5p mimic via inhibiting erythropoietin expression exacerbated Bax-mediated apoptosis, whereas miR-122-5p inhibitor via upregulating erythropoietin and Bcl-2 expression reduced apoptosis. In summary, intrarenal arterial DEX-MV conferred further therapeutic potential to reduce renal IR injury through the miR-122-5p/erythropoietin/apoptosis axis.

Micromixing devices often utilize complex architectures to mix miscible liquid streams and can be complex and expensive to fabricate. Here, we developed, built, experimentally tested, and computationally analyzed a serpentine micromixer that can be fabricated using simple tools and supplies available in non-microdevice dedicated laboratories. Fluorescence imaging was used to quantify its mixing effectiveness experimentally. A Computational Fluid Dynamics (CFD) software package (COMSOL) was used to model the micromixing process. The predictions were in excellent agreement with the experimental data. The serpentine micromixer can achieve significant levels of mixing efficiency. CFD predictions for a straight microfluidic channel of the same length as the serpentine favorably compared with previous theoretical predictions, indicating that the serpentine's mixing efficiency was vastly superior. Finally, CFD predictions were conducted for different and possibly improved designs of the basic serpentine. In all cases, the mixing efficiency was primarily associated with the number of 90o elbows in the device rather than the straight sections' length, with the first serpentine bend playing a significant role. Future design improvements should focus on incorporating as many elbows as possible in the device to maximize mixing efficiency and reduce the device size.

Stretchable electronics have received great attention in recent years because they are able to accommodate large mechanical deformation without damage to their electronic properties. These features are highly desirable for novel applications, including wearable devices, health-monitoring electronics, electronic skin, and artificial neural devices. A key factor in the area of stretchable electronics is the development of intrinsically stretchable polymer semiconductors. This review will survey different approaches that can significantly enhance the stretchability of polymer semiconductors without sacrificing their charge-transport properties. To develop stretchable polymer semiconductors, two approaches have been reported: (1) the engineering of the chemical structures of conjugated polymers; and (2) the physical blending of conjugated polymers in an elastomeric matrix. In addition to these two approaches, the influence of the fabrication process (e.g., solution shearing, nanoconfinement, and electrospinning) on the mechanical and electrical properties of polymer semiconductor films is also reviewed. In the final part, we will introduce novel applications of stretchable polymer semiconductors (e.g., electronic skin, artificial neural electronics, and self-healing polymer semiconductors) and the challenges facing these emerging technologies. This review provides a comprehensive introduction to the development of intrinsically stretchable polymer semiconductors covering molecular design, solution processes, and novel applications.

The discrete steps of transcriptional rewiring have been proposed to occur neutrally to ensure steady gene expression under stabilizing selection over long time-scales, especially when a regulon is being transferred from one transcription factor (TF) to another. Cooperative DNA binding between redundant regulatory components at the intermediate transition stage is believed to mediate this process, enabling a conflict-free switch between two TFs without a disruptive change in gene expression. Here, we have performed an evolutionary repair experiment on the Lachancea kluyveri yeast sef1Δ mutant by means of a suppressor development strategy. Complete loss of SEF1 forced cells to activate a rewiring process to compensate for the pleiotropic defects arising from misexpression of multiple TCA cycle genes. Using different selective conditions, we identified one generalist and one specialist suppressive loss-of-function mutation of IRA1 and AZF1, respectively. Our subsequent analyses show that Azf1 is a weak transcriptional activator regulated by the Ras1-PKA pathway. Azf1 loss-of-function triggers extensive gene expression changes responsible for both the compensatory and trade-off phenotypes. Our results indicate that the pleiotropic effects of dual perturbation of transcriptional networks are a potential mechanism for rapid adaptive compensation, facilitating the process of incipient transcriptional rewiring, and formation of complex traits.

Trichloroethylene (TCE) was once a widely applied industrial solvent, but is now an infamous contaminant in groundwater. Although anaerobic reductive dechlorination is considered a greener remediation approach, the accumulation of toxic intermediates, such as vinyl chloride (VC), and a longer remediation period are highly concerning. Biostimulation and bioaugmentation have been developed to solve these problems. The former method may not be effective, and the latter may introduce foreign genes. Here, we propose a new approach by applying environmental stresses to reshape the indigenous microbiome. In this study, by using the Taguchi method, the effects of heating, pH, salinity, and desiccation were systematically examined. The optimum conditions were defined as 50 °C, pH 9, 3.50% salinity (w/v), and 21% volumetric water content (θ

A huge challenge for developing self-healing materials is achieving a good compromisation between mechanical properties and self-healing efficiency. For this purpose, a facile route by introducing ...

The two liquid-water states, which lead to some anomalies when temperature crosses over 50 ± 10 °C at the atmospheric pressure, have been continuously catching popular attention. In this study, using the excited-state proton transfer (ESPT) catalyzed by water molecules as a prototypical reaction, we demonstrate that the kinetics of ESPT indeed is influenced by the two liquid-water states. In the water-catalyzed ESPT of 3-cyano-7-azaindole (3CAI), a repetitive and comprehensive temperature-dependent study of ESPT in H2O from 0 to 90 °C shows anomalous behavior. The plot of the logarithm of ESPT rate constant as a function of inverse of absolute temperature deviates from a straight line. The convex-Arrhenius behavior manifests the activation free energy for water-assisted ESPT being dependent on temperature and hence the liquid water structure. To simplify the discussion, the plot is well fitted by using two straight lines that are crossed over in the vicinity of 40 °C. The free energy difference between water-solvated 3CAI and the 1:1 H2O:3CAI complex is deduced to be 2.29 ± 0.04 and 1.96 ± 0.04 kcal·mol-1 in the regions of 0-40 and 40-90 °C water, respectively, which also results in different frequency factors, i.e., the proton transfer/tunneling rates of (5.83 ± 0.36) × 1010 and (3.48 ± 0.27) × 1010 s-1, respectively. In a qualitative manner, the results are then rationalized by the different types of H-bonding configuration as proposed for two liquid-water phases, rendering experimental evidence to support the different water phases in ambient temperatures at 1 bar.

An easy and novel synthetic concept for building intrinsically stretchable and elastic semiconducting polymers is designed in this study, in which a conjugated rod–coil block copolymer with a rigid...

Microfluidic devices are constructed from polydimethylsiloxane (PDMS) due to their biocompatibility, fabrication ease, well-established protocols, and simplicity. PDMS-based microfluidic devices are constructed by (i) applying liquid PDMS to a negative mold (usually a silicon or 3D-printed mold) and (ii) curing the PDMS with heat exposure over a set time period. Unreacted resin monomers in 3D-printed molds prevent PDMS from fully curing, resulting in improper channel formation in PDMS and reducing the PDMS device’s efficacy. An in-house protocol that uses SU-8 as a “non-stick” coating on 3D-printed molds facilitates the successful casting of PDMS. Contact angle, surface profile, optical profile, and force testing prove that PDMS cast from SU-8-treated molds resembles pristine PDMS, unlike PDMS cast from untreated molds. Further, this method is generalized to commercial 3D prints using different 3D printing resins. To demonstrate this technique’s viability in microfluidic devices, a microfluidic tree using PDMS from treated 3D prints shows vibrant colors and clear lines. This is absent from an untreated PDMS.

We herein aim to probe the emission quenched by O2 on silica gel. Our special focus is on the O2 quenching of the fluorescence of a series of organic D–π–A phosphonium compounds 1–3. The results show that the O2 quenching rate constants for the fluorescence of 1–3 are on the order of 1010 M−1 s−1, which are nearly on the same order as those measured for 1–3 and common organic compounds in solution. In yet another approach, the study of O2 quenching of phosphorescence in the solid phase indicates that the O2 quenching rate constant for the triplet state, i.e., , is smaller than by two orders of magnitude. Detailed investigation indicates that this distinction stems from the intrinsic O2 quenching rate constants for the singlet and triplet states subsequent to the formation of collisional complexes. In the absence of the solvent cage effect, is greatly influenced by the formation energy of the O2–dye CT complex, whereas in the solid phase is a nearly diffusion-controlled rate. Due to the larger distinction between and in the solid phase, O2 quenching of fluorescence is efficient for dyes in the solid phase. This leads to a feasible application of sensing O2 with regular fluorescent dyes adsorbed on porous solid substrates.

This review paper presents the recent developments in spectroelectrochemical (SEC) technologies. The coupling of spectroscopy and electrochemistry enables SEC to do a detailed and comprehensive study of the electron transfer kinetics and vibrational spectroscopic fingerprint of analytes during electrochemical reactions. Though SEC is a promising technique, the usage of SEC techniques is still limited. Therefore, enough publicity for SEC is required, considering the promising potential in the analysis fields. Unlike previously published review papers primarily focused on the relatively frequently used SEC techniques (ultraviolet-visible SEC and surface-enhanced Raman spectroscopy SEC), the two not-frequently used but promising techniques (nuclear magnetic resonance SEC and dark-field microscopy SEC) have also been studied in detail. This review paper not only focuses on the applications of each SEC method but also details their primary working mechanism. In short, this paper summarizes each SEC technique’s working principles, current applications, challenges encountered, and future development directions. In addition, each SEC technique’s applicative research directions are detailed and compared in this review work. Furthermore, integrating SEC techniques into microfluidics is becoming a trend in minimized analysis devices. Therefore, the usage of SEC techniques in microfluidics is discussed.

Chronic kidney disease (CKD) progression may be evoked through dysregulated mitochondrial dynamics enhanced oxidative stress and inflammation contributing to high cardiovascular morbidity and mortality. Previous study has demonstrated sodium thiosulfate (STS, Na2S2O3) could effectively attenuate renal oxidative injury in the animal model of renovascular hypertension. We explored whether the potentially therapeutic effect of STS is available on the attenuating CKD injury in thirty-six male Wistar rats with 5/6 nephrectomy. We determined the STS effect on reactive oxygen species (ROS) amount in vitro and in vivo by an ultrasensitive chemiluminescence-amplification method, ED-1 mediated inflammation, Masson’s trichrome stained fibrosis, mitochondrial dynamics (fission and fusion) and two types of programmed cell death, apoptosis and ferroptosis by western blot and immunohistochemistry. Our in vitro data showed STS displayed the strongest scavenging ROS activity at the dosage of 0.1 g. We applied STS at 0.1 g/kg intraperitoneally 5 times/week for 4 weeks to these CKD rats. CKD significantly enhanced the degree in arterial blood pressure, urinary protein, BUN, creatinine, blood and kidney ROS amount, leukocytes infiltration, renal 4-HNE expression, fibrosis, dynamin-related protein 1 (Drp1) mediated mitochondrial fission, Bax/c-caspase 9/c-caspase 3/poly (ADP-ribose) polymerase (PARP) mediated apoptosis, iron overload/ferroptosis and the decreased xCT/GPX4 expression and OPA-1 mediated mitochondrial fusion. STS treatment significantly ameliorated oxidative stress, leukocyte infiltration, fibrosis, apoptosis and ferroptosis and improved mitochondrial dynamics and renal dysfunction in CKD rats. Our results suggest that STS as drug repurposing strategy could attenuate CKD injury through the action of anti-mitochondrial fission, anti-inflammation, anti-fibrosis, anti-apoptotic, and anti-ferroptotic mechanisms.

An NP-μFEC is a reusable, novel microfluidic electrochemical cell with multiple non-planar interdigitated microelectrode arrays, minimal sample volume, and enhanced electric field penetration for highly sensitive electrochemical analysis. (i) The NP-μFEC features spatial 3-electrode architecture, and a small sample volume (∼4 μL). (ii) Here, [Fe(CN)

Negative air ions (NAIs) being bioactive and negative charged molecules may confer antioxidant and anti-inflammatory activity. We assessed the effect of NAIs on two inflammatory diseases in animal models including lipopolysaccharide (LPS) induced acute lung injury (ALI) and wound healing in diabetic rats. We used intra-tracheal infusion of LPS to induce ALI and made a full-thickness cutaneous wound in streptozotocin-induced diabetic female Wistar rats. We evaluated NAIs effects on reactive oxygen species amount, leukocyte infiltration, wound healing rate, western blot, and immunohistochemistry in the lungs of ALI and skin sections of wounds. Our data found NAIs exposed saline displayed higher antioxidant activity vs. non-exposed saline. NAIs exposure did not significantly affect arterial blood pressure and respiratory frequency in control and LPS treated groups. LPS increased leukocyte infiltration, caspase 3/Poly-ADP-ribose-polymerase-mediated apoptosis formation and decreased Beclin-1/LC3-II-mediated autophagy in lungs. NAIs exposure conferred pulmonary protection by depressed leukocyte infiltration and caspase 3/Poly-ADP-ribose-polymerase mediated apoptosis and enhanced LC3-II-mediated autophagy in LPS induced ALI. NAIs treatment resulted in a significantly accelerated wound closure rate, decreased erythrocyte accumulation and leukocyte infiltration mediated oxidative stress and inflammation, and upregulated expression of skin collagen, vascular endothelial growth factor receptor-2 (VEGFR-2) and factor transforming growth factor-beta 1 (TGF-β1) vs non-treated group. Based on these results, it is suggested that NAIs conferred a protection through the upregulating LC3-II-dependent autophagy mechanism and downregulating leukocyte infiltration mediated inflammation and caspase 3/Poly-ADP-ribose-polymerase signaling in the LPS-treated ALI and promoted diabetic wound healing through the enhancing skin collagen synthesis, VEGFR-2 and TGF-β1 pathways.

In this work we report the use of a gas sensor that can be used in inline configuration for applications like organ-on-a-chip. The key element of the device is a microfluidic channel with a thickness of 140 μm and width of 500 μm. This microfluidic channel is sandwiched between a top and bottom substrate, each substrate containing microelectrodes making this a non-planar interdigitated microelectrode (NP-IμE) configuration. Room temperature ionic liquids (RTILs) are used as electrolyte in the microfluidic channel. Due to the dimensions of the microfluidic channel only low volume of RTILs are required as electrolyte. RTILs can be tuned to selectively capture specific gases. This in addition to other favourable properties such as wide electrochemical window, thermal stability and negligible vapor pressure makes it a good candidate as the selective electrolyte in electrochemical gas sensor. The use of NP-IμE makes the electric field penetrate through the channel. This allows us to register the perturbations in signal caused by absorption of CO2 from the entire cross-section of the channel, thereby increasing the sensitivity of the device (as compared to a planar architecture). 1-ethyl-3-methylimidazolium 2-cyanopyrolide ([EMIM][2-CNpyr]) was used as the RTIL, as it has been shown to be a good sorbent of CO2 with high capacity at low partial pressures due to its chemical affinity. The RTILs exposed to different concentrations of CO2 was injected into the microfluidic channel. Cyclic Voltammetry (CV), Differential pulse voltammetry (DPV) and Electrochemical impedance spectroscopy (EIS) experiments were done using our microfluidic device. During the CV and DPV experiments, RTIL exposed to CO2 shows a reduction peak (of CO2). This along with the changes in EIS spectrum (Nyquist plot) can be used to detect the presence of CO2. We used CO2 as a test gas to analyse the sensitivity of our microfluidic device combined with RTIL. In future we will be using this same setup to sense biomarker gases and other toxic gases by changing the RTIL and tuning its affinity towards the target analytes.

The ESSENCE platform is an electrochemical sensor system that utilizes non-planar porous microelectrode microfluidic chips with a fully programmable fluidic/sample system to be a “portable, automatic, rapid, sensitive, and selective” for different emerging contaminants and liquid biopsy. The system is designed with non-planar porous microelectrode interfaces, containing different functional capturing probes for specific sensing tasks. From our previous report, this 3D non-planar structure has advantages such as increased flow’s convective fluxes and disrupts diffusive processes like the electric double layer (EDL). The porous electrode structure utilized the packing material’s higher Zeta potential than the bare glass surface, resulting in the EDL length will be significantly smaller than the clear channel. Due to a smaller EDL length, the relaxation frequency will increase, which shifts the EIS signal to a higher frequency range (1kHz to 100MHz) and results in a fast response with a higher signal-to-noise ratio in Electrochemical Impedance Spectroscopy (EIS) measurements. From the perspective of electric field penetration, the top-down electric direction covers all the packing sensing areas, providing a generally higher electronic signal response than the traditional planar electrode system, leading to a higher signal-to-noise ratio. A second feature from the perspective of microfluidics is the significant fluidic shear force generated due to flow through the porous electrode surface. This higher shear force on the surface can unbind most false-positive signals generated by non-specific binding, such as physical adhesive or biofouling. These unique benefits provide physical enhancements of sensitivity and selectivity without manipulating the chemical material in the system. Earlier we showed that our detection of the biomolecules like DNA (fM sensitivity, which can distinguish against a mismatched DNA), proteins (breast cancer biomarker p53, fM sensitivity, which can distinguish it against another breast cancer biomarker HER2), PFOS (Perfluorooctanesulfonate, 0.5 ng) under the traditional desktop Electrochemical Impedance Spectroscopy (EIS) analyzer in the total process of hourly. In this talk, we have further developed our previous ESSENCE platform to a modular, automatic, and portable, one-stop instrument for clinicians to screen for infectious diseases, liquid biopsy, and toxin detection to detect emerging pathogens while significantly reducing false positives and false negatives, but also decreasing our detecting process to 15 mins in much more hazard background conditions to meet the criteria of POC. Second, A small (15 cm x 17cm) USB programable fluidic/oscilloscope base with a 15 minutes total detecting protocol is applied to our ESSENCE system for a fast Point-of-care (POC) diagnostic. This portable ESSENCE platform can respond to the measurable EIS signals from the oscilloscope with 25 ul samples size (DNA and HER2 proteins in undiluted artificial Urine) with a fully automatic process at the uM to pM regions in 15 minutes. Each ESSENCE chip is also significantly cheaper than the ELISA; the chip costs about $20 (for an academic lab) and can be reused. Figure 1

The D-π-A type phosphonium salts in which electron acceptor (A=-+ PR3 ) and donor (D=-NPh2 ) groups are linked by polarizable π-conjugated spacers show intense fluorescence that is classically ascribed to excited-state intramolecular charge transfer (ICT). Unexpectedly, salts with π=-(C6 H4 )n - and -(C10 H6 C6 H4 )- exhibit an unusual dual emission (F1 and F2 bands) in weakly polar or nonpolar solvents. Time-resolved fluorescence studies show a successive temporal evolution from the F1 to F2 emission, which can be rationalized by an ICT-driven counterion migration. Upon optically induced ICT, the counterions move from -+ PR3 to -NPh2 and back in the ground state, thus achieving an ion-transfer cycle. Increasing the solvent polarity makes the solvent stabilization dominant, and virtually stops the ion migration. Providing that either D or A has ionic character (by static ion-pair stabilization), the ICT-induced counterion migration should not be uncommon in weakly polar to nonpolar media, thereby providing a facile avenue for mimicking a photoinduced molecular machine-like motion.

Rapid and sensitive detection and quantification of trace and ultra-trace analytes is critical to environmental remediation, analytical chemistry and defense from chemical and biological contaminants. Though affinity based electrochemical sensors have gained immense popularity, they frequently do not meet the requirements of desired sensitivity and detection limits. Here, we demonstrate a complementary luminescence mode that can significantly enhance sensitivity of impedance or voltammetric electrochemical sensors. Our methodology involves using a redox probe, whose luminescence properties change upon changing the oxidation state. By tailoring the system such that these luminescence changes can be correlated with the capture of target analytes, we are able to significantly lower the detection limit and improve the efficiency of detection compared to the electrochemical modes alone. Our proof-of-concept demonstration, using a model system designed for Ca2+ capture, illustrated that the luminescent mode allowed us to lower the limits of detection by three-orders of magnitude compared to the impedance or voltammetric modes alone without requiring any modification of electrode design or cell configuration. Further, the linear ranges of detection are 10−8 to 10−3 M in the voltammetry mode, 10−8 to 10−5 M in the impedance mode and 2.5 × 10−11 to 10−7 M in the luminescent mode, providing a large range of operational flexibility.

BackgroundMDR Elizabethkingia anophelis strains are implicated in an increasing number of healthcare-associated infections worldwide, including a recent cluster of E. anophelis infections in the Midwestern USA associated with significant morbidity and mortality. However, there is minimal information on the antimicrobial susceptibilities of E. anophelis strains or their antimicrobial resistance to carbapenems and fluoroquinolones.ObjectivesOur aim was to examine the susceptibilities and genetic profiles of clinical isolates of E. anophelis from our hospital, characterize their carbapenemase genes and production of MBLs, and determine the mechanism of fluoroquinolone resistance.MethodsA total of 115 non-duplicated isolates of E. anophelis were examined. MICs of antimicrobial agents were determined using the Sensititre 96-well broth microdilution panel method. QRDR mutations and MBL genes were identified using PCR. MBL production was screened for using a combined disc test.ResultsAll E. anophelis isolates harboured the blaGOB and blaB genes with resistance to carbapenems. Antibiotic susceptibility testing indicated different resistance patterns to ciprofloxacin and levofloxacin in most isolates. Sequencing analysis confirmed that a concurrent GyrA amino acid substitution (Ser83Ile or Ser83Arg) in the hotspots of respective QRDRs was primarily responsible for high-level ciprofloxacin/levofloxacin resistance. Only one isolate had no mutation but a high fluoroquinolone MIC.ConclusionsOur study identified a strong correlation between antibiotic susceptibility profiles and mechanisms of fluoroquinolone resistance among carbapenem-resistant E. anophelis isolates, providing an important foundation for continued surveillance and epidemiological analyses of emerging E. anophelis opportunistic infections. Minocycline or ciprofloxacin has the potential for treatment of severe E. anophelis infections.

BackgroundCiliates are an ancient and diverse eukaryotic group found in various environments. A unique feature of ciliates is their nuclear dimorphism, by which two types of nuclei, the diploid germline micronucleus (MIC) and polyploidy somatic macronucleus (MAC), are present in the same cytoplasm and serve different functions. During each sexual cycle, ciliates develop a new macronucleus in which newly fused genomes are extensively rearranged to generate functional minichromosomes. Interestingly, each ciliate species seems to have its way of processing genomes, providing a diversity of resources for studying genome plasticity and its regulation. Here, we sequenced and analyzed the macronuclear genome of different strains ofParamecium bursaria, a highly divergent species of the genusParameciumwhich can stably establish endosymbioses with green algae.ResultsWe assembled a high-quality macronuclear genome ofP.bursariaand further refined genome annotation by comparing population genomic data. We identified several species-specific expansions in protein families and gene lineages that are potentially associated with endosymbiosis. Moreover, we observed an intensive chromosome breakage pattern that occurred during or shortly after sexual reproduction and contributed to highly variable gene dosage throughout the genome. However, patterns of copy number variation were highly correlated among genetically divergent strains, suggesting that copy number is adjusted by some regulatory mechanisms or natural selection. Further analysis showed that genes with low copy number variation among populations tended to function in basic cellular pathways, whereas highly variable genes were enriched in environmental response pathways.ConclusionsWe report programmed DNA rearrangements in theP.bursariamacronuclear genome that allow cells to adjust gene copy number globally according to individual gene functions. Our results suggest that large-scale gene copy number variation may represent an ancient mechanism for cells to adapt to different environments.

We herein aim to probe the emission quenched by O2 on silica gel. Our special focus is on the O2 quenching of the fluorescence of a series of organic D-π-A phosphonium compounds 1-3. The results show that the O2 quenching rate constants for the fluorescence of 1-3 are on the order of 1010 M-1 s-1, which are nearly on the same order as those measured for 1-3 and common organic compounds in solution. In yet another approach, the study of O2 quenching of phosphorescence in the solid phase indicates that the O2 quenching rate constant for the triplet state, i.e., , is smaller than by two orders of magnitude. Detailed investigation indicates that this distinction stems from the intrinsic O2 quenching rate constants for the singlet and triplet states subsequent to the formation of collisional complexes. In the absence of the solvent cage effect, is greatly influenced by the formation energy of the O2-dye CT complex, whereas in the solid phase is a nearly diffusion-controlled rate. Due to the larger distinction between and in the solid phase, O2 quenching of fluorescence is efficient for dyes in the solid phase. This leads to a feasible application of sensing O2 with regular fluorescent dyes adsorbed on porous solid substrates.

Ocean-bottom seismometers (OBSs) were deployed at a shallow water depth (

Additional file 1: Figure S1. De novo assembly of the P. bursaria MAC genome. Figure S2. P. bursaria introns have very conserved 5′ and 3′ splice sites. Figure S3. PFG Southern blot analysis of the genomic DNA of different P. bursaria strains. Figure S4. The extensive chromosome breakage pattern in the MAC. Figure S5. A model showing how highly variable breaking sites lead to non-uniform gene dosage. Figure S6. Contig copy number is uniform in T. thermophila. Different P. bursaria strains show similar patterns of copy number distribution. Figure S7. Conserved GA-rich motifs are found near chromosome breakage sites. Figure S8. DK1 and DK2 strains are the real F1 progeny of Dd1 and KM2.

Additional file 2: Table S1. Basic statistics for the coding regions of the two haplotypes of the Dd1 reference genome. Table S2. Statistics of sequence diversity for different P. bursaria strains compared to the H1 haplotype of Dd1. Table S3. Basic statistics for the intergenic and intron regions on two haplotypes of the reference genome. Table S5. Enriched GO terms for P. bursaria specific genes (p-value ≤0.05 after the Benjamini-Hochberg correction). Table S7. The correlation matrix (Spearman’s correlation coefficient ρ) of the gene copy number between genetically divergent strains. Table S8. Enriched GO terms for the conserved and non-conserved groups of genes (p-value ≤0.05 after the Benjamini-Hochberg correction). Table S9. DNA and RNA sequencing library list and data accession numbers. Table S10. Primer list used in qPCR and Southern blot and F1 progeny validation.

Exendin-4 (Ex-4) is an incretin mimetic agent approved for diabetes treatment and neuronal protection. However, the required frequent injections restrict its clinical application. We prepared Ex-4-loaded poly(d,l-lactide-co-glycolide) nanoparticles (PEx-4) and investigated their effect on cerebral ischemia/reperfusion (IR) injury associated with micturition center damage-induced cystopathy in diabetic rats. Using ten minutes of bilateral carotid artery occlusion combined with hemorrhage-induced hypotension of the IR model in streptozotocin-induced type 1 diabetic (T1DM) Wistar rats, we compared the effects of Ex-4 and PEx-4 on prefrontal cortex edema, voiding function and oxidative stress including cerebral spinal fluid (CSF) reference H2O2 (RH2O2) and HOCl (RHOCl) levels, endoplasmic reticulum (ER) stress, apoptosis, autophagy and pyroptosis signaling in brain and bladder by Western blot and immunohistochemistry. Single injection of PEx-4 displayed higher CSF antioxidant activity and a long-lasting hypoglycemic effect compared to Ex-4 in rats. T1DM and IR primarily enhanced CSF RH2O2, and pIRE-1/caspase-12/pJNK/CHOP-mediated ER stress, caspase-3/PARP-mediated apoptosis, Beclin-1/LC3B-mediated autophagy and caspase-1/IL-1β-mediated pyroptosis signaling in the damaged brains. Our data further evidenced that PEx-4 were more efficient than Ex-4 in attenuating IR-evoked prefrontal cortex edema, the impairment in micturition center and the enhanced level of CSF RH2O2 and HOCl, ER stress, apoptosis, autophagy and pyroptosis parameters in the damaged brains, but had less of an effect on IR-induced voiding dysfunction in bladders of T1DM rats. In summary, PEx-4 with stronger antioxidant activity and long-lasting bioavailability may efficiently confer therapeutic efficacy to ameliorate IR-evoked brain damage through the inhibitory action on oxidative stress, ER stress, apoptosis, autophagy and pyroptosis signaling in diabetic rats.

Background/Purpose: To compare shear modulus of heel pad microchamber and macrochamber layers between young and elderly people using shear wave ultrasound elastography (SWUE), with the intent to clarify age-related changes. Methods: This single-center prospective cross-sectional study was conducted between March, 2014 and March, 2016. Shear modulus of entire heel pad (Gentire), macrochamber layer (Gmac), and microchamber layer (Gmic) were measured with SWUE. Results: Elderly participants (15 men, 15 women; age = 66.9 ± 6.2 years) had significantly higher Gmic (103.8 ± 20.7 vs. 60.1 ± 9.8 kPa; p

A simple and efficient strategy to modulate the self-assembly and solid-state morphology of conjugated polymers has been developed by incorporating various amounts of amide-containing alkyl side chains to high charge carrier mobility conjugated polymers based on diketopyrrolopyrrole (DPP). Synthetically easily accessible and tunable, the incorporation of amide-containing side chains is a direct strategy to promote intermolecular hydrogen bonding between polymer chains and tune the solid-state morphology. Incorporation of 5–30 mol % of amides in the conjugated polymers was performed without a drastic decrease of solubility. The incorporation of hydrogen-bonding moieties allowed for an improvement of the charge carrier mobility in organic field-effect transistors (OFET) devices, which achieved a maximum value of 2.46 cm2/(V s) at 5 mol % of amides. Morphological investigation showed that the intermolecular hydrogen bonds formed between adjacent amide moieties directly affected the lamellar packing of the po...

An efficient strategy to modulate the mechanical properties of conjugated polymers has been developed through the incorporation of amide-containing alkyl chains in diketopyrrolopyrrole-based conjugated polymers. The side-chain engineering performed with hydrogen bonding moieties (up to 20 mol% of amide-containing side-chains) was found to reduce the crystallinity of the conjugated polymers in the solid state. Interestingly, this reduction in crystallinity drastically influenced the mechanical properties of the new DPP-polymers, by promoting their stretching ability, reducing the elastic modulus of the polymers, and facilitating the molecular alignment after stretch. The resulting polymers with 10% hydrogen bonding side chains showed a maximum stretchability of 75% elongation, without the appearance of nanoscale cracks, and a detailed investigation of the mechanical properties was performed by a combination of morphological characterization tools, including grazing-incidence X-ray diffraction, polarized UV-Vis spectroscopy and optical/atomic force microscopy to support our finding. Additionally, incorporation of amide-containing side-chains also enabled the regeneration of the conjugated polymer morphology after damage. Our results demonstrate that the introduction of amide-containing alkyl chains is an effective strategy to enhance the mechanical properties of π-conjugated polymers without disrupting the π-conjugation, and to enable new properties such as morphological healing.

Author(s): Lai, Yuan-Yang; Cheng, Yu-Hsuan; Hsieh, Kung-Chiao; Nguyen, Darian; Chew, Keng-Tee; Ramanathan, Lalini; Siegel, Jerome M | Abstract: BackgroundAbnormal striatal dopamine transmission has been hypothesized to cause restless legs syndrome. Dopaminergic drugs are commonly used to treat restless legs syndrome. However, they cause adverse effects with long-term use. An animal model would allow the systematic testing of potential therapeutic drugs. A high prevalence of restless legs syndrome has been reported in iron-deficient anemic patients. We hypothesized that the iron-deficient animal would exhibit signs similar to those in restless legs syndrome patients.MethodsAfter baseline polysomnographic recordings, iron-deficient rats received pramipexole injection. Then, iron-deficient rats were fed a standard rodent diet, and polysomnographic recording were performed for 2 days each week for 4 weeks.ResultsIron-deficient rats have low hematocrit levels and show signs of restless legs syndrome: sleep fragmentation and periodic leg movements in wake and in slow-wave sleep. Iron-deficient rats had a positive response to pramipexole treatment. After the iron-deficient rats were fed the standard rodent diet, hematocrit returned to normal levels, and sleep quality improved, with increased average duration of wake and slow-wave sleep episodes. Periodic leg movements decreased during both waking and sleep. Hematocrit levels positively correlated with the average duration of episodes in wake and in slow-wave sleep and negatively correlated with periodic leg movements in wake and in sleep. Western blot analysis showed that striatal dopamine transporter levels were higher in iron-deficient rats.ConclusionsThe iron-deficient rat is a useful animal model of iron-deficient anemic restless legs syndrome. © 2017 International Parkinson and Movement Disorder Society.

•Survey of 97 MRT/LRT systems.•Statistical tests of 4 key variables.•Scale economies are present.•Affordability matters.•MRT/LRT networks work best in large and dense cities.•MRT/LRT systems with moderate coverage are less successful.

Study ObjectivesRestless legs syndrome (RLS) has been hypothesized to be generated by abnormal striatal dopamine transmission. Dopaminergic drugs are effective for the treatment of RLS. However, long-term use of dopaminergic drugs causes adverse effects. We used iron-deficient (ID) and iron-replacement (IR) rats to address the neuropathology of RLS and to determine if a histamine H3 receptor (H3R) antagonist might be a useful treatment. Histamine H3R antagonists have been shown to decrease motor activity.MethodsControl and ID rats were surgically implanted with electrodes for polysomnographic recording. After 3 days of baseline polysomnographic recordings, rats were systemically injected with the H3R agonist, α-methylhistamine, and antagonist, thioperamide. Recordings were continued after drug injection. Striatal H3R levels from control, ID, and IR rats were determined by western blots. Blood from control, ID, and IR rats was collected for the measurement of hematocrit levels.Resultsα-Methylhistamine and thioperamide increased and decreased motor activity, respectively, in control rats. In ID rats, α-methylhistamine had no effect on motor activity, whereas thioperamide decreased periodic leg movement (PLM) in sleep. Sleep–wake states were not significantly altered under any conditions. Striatal H3R levels were highest in ID rats, moderate to low in IR rats, and lowest in control rats. Striatal H3R levels were also found to positively and negatively correlate with PLM in sleep and hematocrit levels, respectively.ConclusionsA striatal histamine mechanism may be involved in ID anemia-induced RLS. Histamine H3R antagonists may be useful for the treatment of RLS.

Objective: To evaluate the effectiveness of traction in improving low back pain, functional outcome, and disk morphology in patients with herniated intervertebral disks. Data Source: PubMed, Scopus, Embase, and the Cochrane Library were searched from the earliest record to July 2019. Review methods: We included randomized control trials which (1) involved adult patients with low back pain associated with herniated disk confirmed by magnetic resonance imaging or computed tomography, (2) compared lumbar traction to sham or no traction, and (3) provided quantitative measurements of pain and function before and after intervention. Methodological quality was assessed using the physiotherapy evidence database (PEDro) scale and Cochrane risk of bias assessment. Results: Initial searches for literature yielded 3015 non-duplicated records. After exclusion based on the title, abstract, and full-text review, 7 articles involving 403 participants were included for quantitative analysis. Compared with the control group, the participants in the traction group showed significantly greater improvements in pain and function in the short term, with standard mean differences of 0.44 (95% confidence interval (CI): 0.11–0.77) and 0.42 (95% CI: 0.08–0.76), respectively. The standard mean differences were not significant to support the long-term effects on pain and function, nor the effects on herniated disk size. Conclusion: Compared with sham or no traction, lumbar traction exhibited significantly more pain reduction and functional improvements in the short term, but not in the long term. There is insufficient evidence to support the effect of lumbar traction on herniated disk size reduction.

Author(s): Zhang, S; Ocheje, MU; Huang, L; Galuska, L; Cao, Z; Luo, S; Cheng, YH; Ehlenberg, D; Goodman, RB; Zhou, D; Liu, Y; Chiu, YC; Azoulay, JD; Rondeau-Gagne, S; Gu, X | Abstract: Organic semiconducting donor–acceptor polymers are promising candidates for stretchable electronics owing to their mechanical compliance. However, the effect of the electron-donating thiophene group on the thermomechanical properties of conjugated polymers has not been carefully studied. Here, thin-film mechanical properties are investigated for diketopyrrolopyrrole (DPP)-based conjugated polymers with varying numbers of isolated thiophene moieties and sizes of fused thiophene rings in the polymer backbone. Interestingly, it is found that these thiophene units act as an antiplasticizer, where more isolated thiophene rings or bigger fused rings result in an increased glass transition temperature (T g ) of the polymer backbone, and consequently elastic modulus of the respective DPP polymers. Detailed morphological studies suggests that all samples show similar semicrystalline morphology. This antiplasticization effect also exists in para-azaquinodimethane-based conjugated polymers, indicating that this can be a general trend for various conjugated polymer systems. Using the knowledge gained above, a new DPP-based polymer with increased alkyl side chain density through attaching alky chains to the thiophene unit is engineered. The new DPP polymer demonstrates a record low T g , and 50% lower elastic modulus than a reference polymer without side-chain decorated on the thiophene unit. This work provides a general design rule for making low-T g conjugated polymers for stretchable electronics.

Background Technology-assisted gait training (TAGT) with body weight support (BWS) has been designed to provide high numbers of repetitions during stepping practice, but its benefits have been inconclusive. Objective We evaluated the superiority of TAGT over conventional overground training (COT) to judge the clinical benefits. Methods We searched PubMed, Embase and Web of Science databases from their earliest record to July 1, 2019 and included randomized controlled trials of TAGT with BWS, such as robot-assisted gait training and body weight-supported treadmill training, for treating walking disability in patients within 6 months after stroke. We conducted a meta-analysis of the outcomes motor impairment, mobility capacity, walking speed, endurance and fitness, balance, and activities of daily living as well as subgroup analyses of initial ambulatory ability and stroke duration. Results Among 14 robotics and 10 body weight-supported treadmill studies included for review, 23 studies involving 1452 participants contributed to the meta-analysis. We found no significant standardized mean differences between TAGT and COT (P > 0.05) across all outcome categories in the robotics subgroup, the body weight-supported treadmill subgroup, or both subgroups combined, for both the short and long term. Further subgroup analyses also revealed non-significant standardized mean differences (P > 0.05) across all outcomes in the subgroups initially ambulatory, non-ambulatory, or stroke duration less than 3 months. Conclusions TAGT with BWS was not superior to COT in improving post-stroke recovery in patients with subacute stroke. Strategies other than simply increasing the repetitions by external assistance may be considered to augment the treatment effects of TAGT.

The rapid, sensitive, and selective detection of target analytes using electrochemical sensors is challenging. ESSENCE, a new Electrochemical Sensor that uses a Shear-Enhanced, flow-through Nanoporous Capacitive Electrode, overcomes current electrochemical sensors' response limitations, selectivity, and sensitivity limitations. ESSENCE is a microfluidic channel packed with transducer material sandwiched by a top and bottom microelectrode. The room-temperature instrument less integration process allows the switch of the transducer materials to make up the porous electrode without modifying the electrode architecture or device protocol. ESSENCE can be used to detect both biomolecules and small molecules by simply changing the packed transducer material. Electron microscopy results confirm the high porosity. In conjunction with the non-planar interdigitated electrode, the packed transducer material results in a flow-through porous electrode. Electron microscopy results confirm the high porosity. The enhanced shear forces and increased convective fluxes disrupt the electric double layer's (EDL) diffusive process in ESSENCE. This disruption migrates the EDL to high MHz frequency allowing the capture signal to be measured at around 100 kHz, significantly improving device timing (rapid detection) with a low signal-to-noise ratio. The device's unique architecture allows us multiple configuration modes for measuring the impedance signal. This allows us to use highly conductive materials like carbon nanotubes. We show that by combining single-walled carbon nanotubes as transducer material with appropriate capture probes, NP-μIDE has high selectivity and sensitivity for DNA (fM sensitivity, selective against non-target DNA), breast cancer biomarker proteins (p53, pg/L sensitivity, selective against non-target HER2).

We report the functionalized carbon nanotubes (fCNTs) and graphene oxide (GO) doped polyvinyl alcohol (PVA) based gel electrolytes (GEs). The multiwalled carbon nanotubes (CNTs) were treated via microwave irradiation to alter the degree of carboxylation. The fCNT doped gel electrolyte (fCNTGE) showed significantly improved ionic conductivity, mechanical strength as well as electrochemical stability when compared to the pure GE and graphene oxide doped gel electrolyte (GOGE). The homogeneous distribution of ionic channels provided by fCNTs served as redox shuttle and facilitated the ion migration in the gel. The fCNTGE exhibited the best performance when the oxygen content was 12.8% by weight. The ionic conductivity was significantly improved by introducing fCNTs into the PVA gel and reached 6.9 × 10−2 S cm−1, revealing that the diffusion and transport of ions into electrolyte were much better than the GE and GOGE. A significant enhancement in the gel mechanical properties was observed as the Young's module (E = 2.3) and tensile strength (22.3 kPa) of fCNTGE was higher than that of GE and GOGE. Furthermore, the composite Zn–Ag2O batteries were made and tested using the fCNTGE, GE, and GOGE in the 3D-printed battery casings. The fCNTGE based batteries demonstrated good electrochemical stability with specific capacity reaching 204.3 mAh g−1 (C/20).