Search

Mohammad Rabiul Halim,1,&ast; Shuvajit Saha,2,&ast; Injamam Ull Haque,1 Sadia Jesmin,1 Rahatul Jannat Nishat,3 ASMD Ashraful Islam,2 Seema Roy,4 Miah Md Akiful Haque,5 Md Motiul Islam,1 Tarikul Hamid,1 Kazi Nuruddin Ahmed,1 Md Azharul Islam Talukder,1 Arif Ahmed,1 Emran Hasan,2 Nurjahan Ananna,1 Faroque Md Mohsin,6 Mohammad Delwer Hossain Hawlader7 1Department of Critical Care Medicine, Central Police Hospital, Dhaka, Bangladesh; 2Department of Maternal and Child Health, Projahnmo Research Foundation, Dhaka, Bangladesh; 3Department of Physiology, Sir Salimullah Medical College, Dhaka, Bangladesh; 4Department of Medicine, Popular Medical College, Dhaka, Bangladesh; 5Department of Epidemiology, Public Health Professional Development Initiative (PPDI), Dhaka, Bangladesh; 6Directorate General of Health Services (DGHS), Ministry of Health and Family Welfare, Dhaka, Bangladesh; 7Department of Public Health, North South University, Dhaka, Bangladesh&ast;These authors contributed equally to this workCorrespondence: Mohammad Delwer Hossain Hawlader Email mohammad.hawlader@northsouth.eduPurpose: The world is heavily suffering from the COVID-19 pandemic for more than a year, with over 191 million confirmed cases and more than 4.1 million deaths to date. Previous studies have explored several risk factors for coronavirus disease 2019 (COVID-19), but there is still a lack of association with ABO blood type. This study aimed to find out the relationship between the ABO blood group and COVID-19 outcomes in Bangladesh.Subjects and Methods: This retrospective cross-sectional study was conducted in the intensive care unit (ICU) of a tertiary-level COVID-dedicated hospital in Dhaka city, Bangladesh, between April 2020 and November 2020. Records from 771 critically ill patients were extracted who were confirmed for COVID-19 by reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and blood grouping records were available in the health records.Results: The blood groups were 37.35%, 17.38%, 26.46%, and 18.81% for A, B, AB, and O type, respectively. Clinical symptoms were significantly more common in patients with blood type A (p < 0.05). Patients with blood type A had higher WBC counts and peak serum ferritin levels and both were statistically significant (p < 0.001). Patients with blood type A had a greater need for supplemental oxygen, and they were more likely to die in comparison to the patients with other blood types (p < 0.05). In multivariable analysis, our primary outcome death was significantly associated with blood type A (AOR: 3.49, 95% CI: 1.57– 7.73) while adjusting for age, male gender, and non-communicable diseases.Conclusion: Based on this study results, it can be concluded that the COVID-19 patients with blood type A have a higher chance of death and other complications. The authors recommend blood grouping before treating the COVID-19 patients, and healthcare workers should prioritize treating the patients based on that result.Keywords: COVID-19, ICU, ABO blood group, Bangladesh

Chemical dispersants is one of the globally accepted remediation technique used for marine oil spill. However, the toxicity related with these dispersants confined its application in marine environment. Therefore, to overcome this problem, the employment of environmentally benign dispersants is one of the effective conceivable approach. In this study, the formulation comprised of choline based ionic liquid, choline laurate ([Cho][Lau]) and a biosurfactant, lactonic sophorolipids (LS) were used as a crude oil emulsifier. The toxicity of the newly developed formulation was evaluated to confirm their safe employment in sea water. The developed formulation worked effectively as a crude oil emulsifier and formed a stable crude oil emulsion. The toxicity study against Gram-positive and -negative bacteria depicts the “practically harmless” nature of the developed formulation. Thus, the results presented in this study showed that the new formulation can potentially replace the conventional dispersant used for marine oil spill remediation.

Objective: Diabetes is a metabolic disorder that causes the risk of stroke, heart disease, kidney failure, and other long-term complications because diabetes generates excess sugar in the blood. Machine learning (ML) models can aid in diagnosing diabetes at the primary stage. So, we need an efficient ML model to diagnose diabetes accurately., Methods: In this paper, an effective data preprocessing pipeline has been implemented to process the data and random oversampling to balance the data, handling the imbalance distributions of the observational data more sophisticatedly. We used four different diabetes datasets to conduct our experiments. Several ML algorithms were used to determine the best models to predict diabetes faultlessly., Results: The performance analysis demonstrates that among all ML algorithms, random forest surpasses the current works with an accuracy rate of 86% and 98.48% for Dataset 1 and Dataset 2; extreme gradient boosting and decision tree surpass with an accuracy rate of 99.27% and 100% for Dataset 3 and Dataset 4, respectively. Our proposal can increase accuracy by 12.15% compared to the model without preprocessing., Conclusions: This excellent research finding indicates that the proposed models might be employed to produce more accurate diabetes predictions to supplement current preventative interventions to reduce the incidence of diabetes and its associated costs., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Hypopharyngeal cancer is a disease that is associated with EGFR-mutated lung adenocarcinoma. Here we utilized a bioinformatics approach to identify genetic commonalities between these two diseases. To this end, we examined microarray datasets from GEO (Gene Expression Omnibus) to identify differentially expressed genes, common genes, and hub genes between the selected two diseases. Our analyses identified potential therapeutic molecules for the selected diseases based on 10 hub genes with the highest interactions according to the degree topology method and the maximum clique centrality (MCC). These therapeutic molecules may have the potential for simultaneous treatment of these diseases., (© 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Due to its improved localization and confinement of light in single or multiple wavelength modes, nanolasers based on plasmonic crystals have grown in popularity in recent years. However, the lasing modes are not spatially separated, making applying different modes to different applications difficult. This work demonstrates an effective technique for spatially separating the two modes of a merged lattice metal nanohole array-based dual-mode plasmonic laser. A flat dielectric metasurface-based beam-splitter that exploits phase gradient profiles on the interfaces has been added to the laser to separate the modes into distinct spatial beams. The proposed structure successfully separates two modes by ∼23°, and the separation can be raised to ∼63° by tuning structural parameters such as the radius of the nanocylinders and the number of supercell rows. In addition, multiple beams can be generated, allowing for manual beam steering. This approach has a high emission output with a narrow linewidth, clarity, and a substantial degree of future tunability potential. The proposed integrated structure will provide a novel means of device miniaturization and may also serve advanced optical applications such as optical communication, quantum optics, interferometry, spectroscopy, and light detection and ranging (LiDAR).

We propose Tamm plasmon (TP) and surface plasmon (SP) hybrid modes for hemoglobin (Hb) detection in anisotropic graphene-photonic-crystal (GPC) structures. The proposed GPC sensor shows polarization-dependent responses due to the in-plane anisotropic property. The reflection profiles of the proposed sensor exhibit two reflectivity minima due to the simultaneous excitation of TP and SP modes. When used to detect Hb, the TP mode offers a greater figure-of-merit (FoM) than the SP mode. Using a Fourier mode spectral analysis, we observe energy coupling from the TP to the SP mode when the incident light's polarization changes, providing an option to enhance the sensor's sensitivity. We propose a double dips method (DDM) to detect Hb based on the simultaneous excitation of TP and SP modes. Using DDM, the proposed sensor offers a maximum sensitivity of 314.5 degrees/RIU and a FoM of 1746 RIU -1 when the Hb level is 189 g/L. The proposed anisotropic GPC sensor offers possible applications for highly sensitive bio-molecule detection with high FoM.

The worldwide COVID-19 pandemic has profoundly influenced the health and everyday experiences of individuals across the planet. It is a highly contagious respiratory disease requiring early and accurate detection to curb its rapid transmission. Initial testing methods primarily revolved around identifying the genetic composition of the coronavirus, exhibiting a relatively low detection rate and requiring a time-intensive procedure. To address this challenge, experts have suggested using radiological imagery, particularly chest X-rays, as a valuable approach within the diagnostic protocol. This study investigates the potential of leveraging radiographic imaging (X-rays) with deep learning algorithms to swiftly and precisely identify COVID-19 patients. The proposed approach elevates the detection accuracy by fine-tuning with appropriate layers on various established transfer learning models. The experimentation was conducted on a COVID-19 X-ray dataset containing 2000 images. The accuracy rates achieved were impressive of 99.55%, 97.32%, 99.11%, 99.55%, 99.11% and 100% for Xception, InceptionResNetV2, ResNet50 , ResNet50V2, EfficientNetB0 and EfficientNetB4 respectively. The fine-tuned EfficientNetB4 achieved an excellent accuracy score, showcasing its potential as a robust COVID-19 detection model. Furthermore, EfficientNetB4 excelled in identifying Lung disease using Chest X-ray dataset containing 4,350 Images, achieving remarkable performance with an accuracy of 99.17%, precision of 99.13%, recall of 99.16%, and f1-score of 99.14%. These results highlight the promise of fine-tuned transfer learning for efficient lung detection through medical imaging, especially with X-ray images. This research offers radiologists an effective means of aiding rapid and precise COVID-19 diagnosis and contributes valuable assistance for healthcare professionals in accurately identifying affected patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This work focuses on the utilization of counter-propagating plane waves for optical manipulation, which provides a unique approach to control the behavior of Rayleigh and Dipolar nanoparticles immersed in a homogeneous or heterogeneous medium. Our study presents an interesting finding of a repulsive force between plasmonic-chiral heterodimers where the particles move away from each other in both near and far field regions. Interestingly, this repulsive thrust supports the wave like nature of light for the case of homogeneous background but particle type nature of light for heterogenous background. At first, we have investigated the theory underlying the optical trapping of the chiral particle and the impact of this phenomenon on the overall repulsive behavior of the heterodimers placed in air (homogeneous) background. After that, our proposed set-up has further been investigated putting in air-water interface (heterogenous background) and by varying light angle only a little bit. Our observation for this interface case is suggesting the transfer of Minkowski momentum of photon to each optically pulled Rayleigh or dipolar particle of the dimer set, which ultimately causes a broad-band giant repulsive thrust of the dimers. However, in absence of the other particle in the cluster, a single half-immersed particle does not experience the pulling force for the broad-band spectrum. The 'common' reason of the observed repulsive thrust of the dimers for both the aforementioned cases has been attributed to "modified" longitudinal Optical Binding Force (OBF). Technically, this work may open a new way to control the repulsion and attraction between the nanoparticles both in near and far field regions by utilizing the background and the counter-propagating waves. We also believe that this work manifests a possible simple set-up, which will support to observe a background dependent wave 'or' particle nature of light experimentally., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Biswas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Biomarker-based cancer identification and classification tools are widely used in bioinformatics and machine learning fields. However, the high dimensionality of microarray gene expression data poses a challenge for identifying important genes in cancer diagnosis. Many feature selection algorithms optimize cancer diagnosis by selecting optimal features. This article proposes an ensemble rank-based feature selection method (EFSM) and an ensemble weighted average voting classifier (VT) to overcome this challenge. The EFSM uses a ranking method that aggregates features from individual selection methods to efficiently discover the most relevant and useful features. The VT combines support vector machine, k-nearest neighbor, and decision tree algorithms to create an ensemble model. The proposed method was tested on three benchmark datasets and compared to existing built-in ensemble models. The results show that our model achieved higher accuracy, with 100% for leukaemia, 94.74% for colon cancer, and 94.34% for the 11-tumor dataset. This study concludes by identifying a subset of the most important cancer-causing genes and demonstrating their significance compared to the original data. The proposed approach surpasses existing strategies in accuracy and stability, significantly impacting the development of ML-based gene analysis. It detects vital genes with higher precision and stability than other existing methods.

Topical application of honey results in disinfecting the wound infection promptly and also expedites healing. Being cheap and widely available, honey can be an excellent alternative to be used as a topical antimicrobial agent. This study observes the in vitro growth inhibitory activity of different concentration of honey for different bacterial strains. This experimental study had been carried out in the Department of Pharmacology and Therapeutics of Sir Salimullah Medical College and Mitford Hospital (SSMC), Dhaka, Bangladesh in collaboration with Microbiology, Department of Sir Salimullah Medical College and Mitford Hospital (SSMC), Dhaka, Bangldesh over a period of one year from July 2018 to June 2019. Using the Agar dilution method to detect the antimicrobial activity of honey on 18 bacterial isolates belong to enterobacteriaceae family namely, 8 bacterial isolates of Salmonella Enterica Serovar Typhi, Five (5) bacterial isolates of Escherichia coli and 5 bacterial isolates of Pseudomonas aeruginosa. The mean of the minimum inhibitory concentration (MIC) of honey for the isolates of Salmonella enterica serovar typhi was 15.35±12.39mg/ml, ranged between 3.56 and 41.6mg/ml (0.25% - 3.0% v/v). In case of the isolates of Escherichia coli the mean MIC of honey recorded at 28.53±16.18mg/ml and the growth was ranged between 7.10 and 48.3mg/ml (0.5% - 3.50% v/v). And the mean of the MIC of honey for the isolates of Pseudomonas aeruginosa was 20.31±13.20mg/ml, ranged between 10.63 and 41.6mg/ml (0.75% - 3.0% v/v). The brilliant antibacterial activity of honey against clinical bacterial isolates indicates the usefulness of honey in clinical practice against bacterial infection.

Precisely detecting the ultra-low-level severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial. The detection mechanism must be sensitive, low-cost, portable, fast, and easy to operate to tackle coronavirus disease 19 (COVID-19). This work proposes a sensor exploiting graphene surface plasmon resonance to detect SARS-CoV-2. The graphene layer functionalized with angiotensin-converting enzyme 2 (ACE2) antibodies will help efficient adsorption of the SARS-CoV-2. In addition to the graphene layer, ultra-thin layers of novel two-dimensional materials tungsten disulfide (WS2), potassium niobate (KNbO3), and black phosphorus (BP) or blue phosphorus (BlueP) used in the proposed sensor will increase the light absorption to detect an ultra-low SARS-CoV-2 concentration. The analysis presented in this work shows that the proposed sensor will detect SARS-CoV-2 as small as ∼1 fM. The proposed sensor also offers a minimum sensitivity of 201 degrees/RIU, a figure-of-merit of 140 RIU-1, and enhanced binding kinetics of the SARS-CoV-2 to the sensor surface., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hossain, Talukder. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Significance: Biological cell imaging has become one of the most crucial research interests because of its applications in biomedical and microbiology studies. However, three-dimensional (3D) imaging of biological cells is critically challenging and often involves prohibitively expensive and complex equipment. Therefore, a low-cost imaging technique with a simpler optical arrangement is immensely needed., Aim: The proposed approach will provide an accurate cell image at a low cost without needing any microscope or extensive processing of the collected data, often used in conventional imaging techniques., Approach: We propose that patterns of surface plasmon coupled emission (SPCE) features from a fluorescently labeled biological cell can be used to image the cell. An imaging methodology has been developed and theoretically demonstrated to create 3D images of cells from the detected SPCE patterns. The 3D images created from the different SPCE properties at the far-field closely match the actual cell structures., Results: The developed technique has been applied to different regular and irregular cell shapes. In each case, the calculated root-mean-square error (RMSE) of the created images from the cell structures remains within a few percentages. Our work recreates the base of a circular-shaped cell with an RMSE of ≲1.4 % . In addition, the images of irregular-shaped cell bases have an RMSE of ≲2.8 % . Finally, we obtained a 3D image with an RMSE of ≲6.5 % for a random cellular structure., Conclusions: Despite being in its initial stage of development, the proposed technique shows promising results considering its simplicity and the nominal cost it would require.

Lasers that can emit two photons from a single electron relaxation between two states of the same parity have been discussed since the early days of the laser era. However, such lasers have seen only limited success, mainly due to a lack of suitable gain medium. We propose that terahertz (THz) frequency quantum cascade lasers (QCLs) are an ideal semiconductor structure to realize such two-photon emissions. In this work, we present a THz QCL heterostructure designed to emit two resonant photons from each electronic relaxation between two same-parity states in the active region. We present coupled Maxwell-Bloch equations that describe the dynamics of such a two-photon laser and find analytical solutions for the steady-state light intensity, the steady-state energy-resolved carrier densities, and the total threshold carrier density. Due to the two-photon emission from each excited state relaxation and an increased photon-driven carrier transport rate, our simulations predict a significant enhancement of light intensity in our designed resonant two-photon THz QCL when compared to an exemplar conventional THz QCL structure.

Miniature lasers emitting dual-wavelength modes have diverse applications alongside the more explored single-mode counterparts. However, having dual-wavelength modes originating from a plasmonic-photonic hybrid laser is still a relatively new area for research. Compared to the amount of literature devoted to the physics of such hybrid cavities, only a few have analyzed their role in lasing applications. Notably, the role of hybrid cavities in dual-wavelength lasing is still unexplored. In this work, the properties of one-dimensional distributed Bragg reflectors and thin metal nanohole arrays come together to create a hybrid dual-mode plasmonic laser. The similar energy distribution characteristics of photonic and plasmonic lasers make hybrid structures a viable choice for efficient dual-mode lasing. In this work, the lasing cavity simultaneously excites photonic and Tamm plasmonic modes to generate dual-mode lasing. Consequently, the proposed laser shows high emission output with narrow linewidth and a clear and tunable mode separation.

Plasmonic lasers offer great potential for cutting-edge, disruptive applications. However, they suffer from a high loss in metals, lack of spatial coherence in the near field, and divergent far-field emission. The challenges are even more significant for a plasmonic laser emitting more than one wavelength mode. The design complexity required for creating multiple modes often limits avenues for minimizing losses and converging far-field emission patterns. This work exploits plasmonic resonances at the junction of a merged lattice metal nanohole array (NHA) and a one-dimensional photonic crystal to achieve dual-mode lasing. The merged lattice NHA is designed by concentrically combining two simple NHAs with different periodicities to create pseudo randomness, leading to enhanced localization and confinement of light in multiple wavelength modes. The proposed structure notably produces intense dual-mode lasing at an ultra-low threshold compared to recent state-of-the-art plasmonic laser demonstrations. The wavelengths of the lasing modes and the separation between them can be tuned over a broad range by changing the structural parameters. The proposed laser also creates a highly directional far-field pattern with a divergence angle of only <0.35°., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

The superior mass sensitivity of microcoil technology in nuclear magnetic resonance (NMR) spectroscopy provides potential for the analysis of extremely small-mass-limited samples such as eggs, cells, and tiny organisms. For optimal performance and efficiency, the size of the microcoil should be tailored to the size of the mass-limited sample of interest, which can be costly as mass-limited samples come in many shapes and sizes. Therefore, rapid and economic microcoil production methods are needed. One method with great potential is 5-axis computer numerical control (CNC) micromilling, commonly used in the jewelry industry. Most CNC milling machines are designed to process larger objects and commonly have a precision of >25 μm (making the machining of common spiral microcoils, for example, impossible). Here, a 5-axis MiRA6 CNC milling machine, specifically designed for the jewelry industry, with a 0.3 μm precision was used to produce working planar microcoils, microstrips, and novel microsensor designs, with some tested on the NMR in less than 24 h after the start of the design process. Sample wells could be built into the microsensor and could be machined at the same time as the sensors themselves, in some cases leaving a sheet of Teflon as thin as 10 μm between the sample and the sensor. This provides the freedom to produce a wide array of designs and demonstrates 5-axis CNC micromilling as a versatile tool for the rapid prototyping of NMR microsensors. This approach allowed the experimental optimization of a prototype microstrip for the analysis of two intact adult Daphnia magna organisms. In addition, a 3D volume slotted-tube resonator was produced that allowed for 2D 1 H- 13 C NMR of D. magna neonates and exhibited 1 H sensitivity ( n LOD ω 600 = 1.49 nmol s 1/2 ) close to that of double strip lines, which themselves offer the best compromise between concentration and mass sensitivity published to date.

Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) analyses of diffusion-weighted magnetic resonance imaging (MRI) show that diffusional fractional anisotropy (FA) and kurtosis anisotropy (KA) of water inside brain white matter decrease for schizophrenic patients from that for healthy persons. DTI and DKI are statistical approaches and do not directly point to the underlying neurobiological reasons. In schizophrenia, it is believed that the demyelination of axons-microstructures that constitute the brain white matter-increases lateral diffusion of water and causes defective neural communications, resulting cognitive processing-speed deficits. Here, we use a simple but realistic neurobiological model for brain white matter and solve the Bloch-Torrey equation using numerical finite-element method to find out the underlying reasons of cognitive deficits in schizophrenia. FA and KA are calculated from computationally obtained diffusion-weighted MRI data after a Stejskal-Tanner gradient pulse sequence is applied to a periodic array of tubular axons with circular cross-sections. The calculated FA and KA decrease when the axon walls are more permeable to water, agree with the experimental findings, and correlate with the cognitive processing speeds of healthy persons and schizophrenic patients, and thus, help to understand the underlying reasons of cognitive processing-speed deficits in schizophrenia.

Distinguishing between whole cells and cell debris is important in microscopy, e.g., in screening of pulmonary patients for infectious tuberculosis. We propose and theoretically demonstrate that whole cells and cell debris can be distinguished from the far-field pattern of surface plasmon coupled emission (SPCE) of a fluorescently-labeled sample placed on a thin metal layer. If fluorescently-labeled whole cells are placed on the metal film, SPCE takes place simultaneously at two or more different angles and creates two or more distinct rings in the far field. By contrast, if fluorescently-labeled cell debris are placed on the metal film, SPCE takes place at only one angle and creates one ring in the far-field. We find that the angular separation of the far-field rings is sufficiently distinct to use the presence of one or more rings to distinguish between whole cells and cell debris. The proposed technique has the potential for detection without the use of a microscope., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Insulin resistance and diabetes are comorbidities of obesity and affect one in 10 adults in the United States. Despite the high prevalence, the mechanisms of cardiac insulin resistance in obesity are still unclear. We test the hypothesis that the insulin receptor localizes to caveolae and is regulated through binding to caveolin-3 (CAV3). We further test whether haploinsufficiency forCAV3 increases the susceptibility to high-fat-induced insulin resistance. We used in vivo and in vitro studies to determine the effect of palmitate exposure on global insulin resistance, contractile performance of the heart in vivo, glucose uptake in the heart, and on cellular signaling downstream of theIR We show that haploinsufficiency forCAV3 increases susceptibility to palmitate-induced global insulin resistance and causes cardiomyopathy. On the basis of fluorescence energy transfer (FRET) experiments, we show thatCAV3 andIRdirectly interact in cardiomyocytes. Palmitate impairs insulin signaling by a decrease in insulin-stimulated phosphorylation of Akt that corresponds to an 87% decrease in insulin-stimulated glucose uptake inHL-1 cardiomyocytes. Despite loss of Akt phosphorylation and lower glucose uptake, palmitate increased insulin-independent serine phosphorylation ofIRS-1 by 35%. In addition, we found lipid induced downregulation ofCD36, the fatty acid transporter associated with caveolae. This may explain the problem the diabetic heart is facing with the simultaneous impairment of glucose uptake and lipid transport. Thus, these findings suggest that loss ofCAV3 interferes with downstream insulin signaling and lipid uptake, implicatingCAV3 as a regulator of theIRand regulator of lipid uptake in the heart., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), and reduced BH4 availability leads to endothelial NOS (eNOS) uncoupling and increased reactive oxygen species (ROS) generation. Questions remain regarding the functional state of eNOS and role of BH4 availability in the process of in vivo myocardial ischemia-reperfusion (I/R) injury. Rats were subjected to 60min of in vivo left coronary artery occlusion and varying periods of reperfusion with or without pre-ischemic liposomal BH4 supplementation (1mg/kg, iv). Myocardial infarction was correlated with cardiac BH4 content, eNOS protein level, NOS enzyme activity, and ROS generation. In the vehicle group, 60-min ischemia drastically reduced myocardial BH4 content in the area at risk (AAR) compared to non-ischemic (NI) area and the level remained lower during early reperfusion followed by recovery after 24-h reperfusion. Total eNOS, activated eNOS protein level (eNOS Ser1177 phosphorylation) and NOS activity were also significantly reduced during ischemia and/or early reperfusion, but recovered after 24-h reperfusion. With liposomal BH4 treatment, BH4 levels were identical in the AAR and NI area during ischemia and/or early reperfusion, and were significantly higher than with vehicle. BH4 pre-treatment preserved eNOS Ser1177 phosphorylation and NOS activity in the AAR, and significantly reduced myocardial ROS generation and infarction compared to vehicle. These findings provide direct evidence that in vivo I/R induces eNOS dysfunction secondary to BH4 depletion, and that pre-ischemic liposomal BH4 administration preserves eNOS function conferring cardioprotection with reduced oxidative stress., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We theoretically show that quantum coherent saturable absorption can be used to obtain ultra-short pulses from mid-infrared quantum cascade lasers (QCLs). In this proposal, quantum cascade structures are processed as two electrically isolated sections. The two sections will be biased with two different voltages so that one of the sections produces gain as is done in typical QCLs, while the other produces quantum coherent resonant absorption for the propagating waves. The quantum coherent absorbing section is saturable and favors the generation of ultra-short pulses. We find that stable ultra-short pulses on the order of ∼100 ps are created from a two-section QCL when the pumping in the gain and absorbing sections remains within critical limits. The intensity and the duration of the stable pulses can be significantly varied when the pumping in the gain and absorbing sections and the length of the gain and absorbing sections are varied.

The GTP-binding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O(2)(·-)). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A novel transgenic mouse model with cardiac-specific overexpression of constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been reported with increased myocardial Rac-GTPase activity and O(2)(·-) generation. The goal of the present study was to determine signaling pathways related to increased myocardial ZmRacD and to what extent hearts with increased ZmRacD proteins are susceptible to I/R injury. The effect of myocardial I/R was examined in young adult wild-type (WT) and ZmRacD transgenic (TG) mice. In vitro reversible myocardial I/R for postischemic cardiac function and in vivo regional myocardial I/R for MI were performed. Following 20-min global ischemia and 45-min reperfusion, postischemic cardiac contractile function and heart rate were significantly reduced in TG hearts compared with WT hearts. Importantly, acute regional myocardial I/R (30-min ischemia and 24-h reperfusion) caused significantly larger MI in TG mice compared with WT mice. Western blot analysis of cardiac homogenates revealed that increased myocardial ZmRacD gene expression is associated with concomitant increased levels of NADPH oxidase subunit gp91(phox), O(2)(·-), and P(21)-activated kinase. Thus these findings provide direct evidence that increased levels of active myocardial Rac renders the heart susceptible to increased postischemic contractile dysfunction and MI following acute I/R.

Aims: The role of endothelial nitric oxide synthase (eNOS)/NO signalling is well documented in late ischaemic preconditioning (IPC); however, the role of eNOS and its activation in early IPC remains controversial. This study investigates the role of eNOS in early IPC and the signalling pathways and molecular interactions that regulate eNOS activation during early IPC., Methods and Results: Rat hearts were subjected to 30-min global ischaemia and reperfusion (I/R) with or without IPC (three cycles 5-min I and 5-min R) in the presence or absence of the NOS inhibitor l-NAME, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (LY), and protein kinase A (PKA) inhibitor H89 during IPC induction or prior endothelial permeablization. IPC improved post-ischaemic contractile function and reduced infarction compared with I/R with this being abrogated by l-NAME or endothelial permeablization. eNOS(Ser1176), Akt(Ser473), and PKA(Thr197) phosphorylation was increased following IPC. I/R decreased eNOS(Ser1176) phosphorylation, whereas IPC increased it. Mass spectroscopy confirmed eNOS(Ser1176) phosphorylation and quantitative Western blots showed ∼24% modification of eNOS(Ser1176) following IPC. Immunoprecipitation demonstrated eNOS, Akt, and PKA complexation. Immunohistology showed IPC-induced Akt and PKA phosphorylation in cardiomyocytes and endothelium. With eNOS activation, IPC increased NO production as measured by electron paramagnetic resonance spin trapping and fluorescence microscopy. LY or H89 not only decreased Akt(Ser473) or PKA(Thr197) phosphorylation, respectively, but also abolished IPC-induced preservation of eNOS and eNOS(Ser1176) phosphorylation as well as cardioprotection., Conclusion: Thus, Akt- and PKA-mediated eNOS activation, with phosphorylation near the C-terminus, is critical for early IPC-induced cardioprotection, with eNOS-derived NO from the endothelium serving a critical role.

There is emerging evidence that treatment with thyroid hormone (TH) can improve postischemic cardiac function. 3,5-Diiodothyropropionic acid (DITPA), a TH analog, has been proposed to be a safer therapeutic agent than TH because of its negligible effects on cardiac metabolism and heart rate. However, conflicting results have been reported for the cardiac effects of DITPA. Importantly, recent clinical trials demonstrated no symptomatic benefit in patients with DITPA despite some improved hemodynamic and metabolic parameters. To address these issues, dose-dependent effects of DITPA were investigated in mice for baseline cardiovascular effects and postischemic myocardial function and/or salvage. Mice were treated with subcutaneous DITPA at 0.937, 1.875, 3.75, or 7.5 mg·kg(-1)·day(-1) for 7 days, and the results were compared with untreated mice for ex vivo and/or in vivo myocardial ischemia-reperfusion (I/R). DITPA had no effects on baseline body temperature, body weight, or heart rate; however, it mildly increased blood pressure. In isolated hearts, baseline contractile function was significantly impaired in DITPA-pretreated mice; however, postischemic recovery was comparable between untreated and DITPA-treated groups. In vivo baseline cardiac parameters were significantly affected by DITPA, with increased ventricular dimensions and decreased contractile function. Importantly, DITPA-treated mice demonstrated high prevalence of fatal cardiac rhythm abnormalities during in vivo ischemia and/or reperfusion. There were no improvements in myocardial infarction and postischemic fractional shortening with DITPA. Myocardial sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and heat shock protein (HSP) levels remained unchanged with DITPA treatment. Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R.

Cigarette smoking is a major independent risk factor for cardiovascular disease. While the association between chronic smoking and cardiovascular disease is well established, the underlying mechanisms are incompletely understood, partly due to the lack of adequate in vivo animal models. Here, we report a mouse model of chronic smoking-induced cardiovascular pathology. Male C57BL/6J mice were exposed to whole body mainstream cigarette smoke (CS) using a SCIREQ "InExpose" smoking system (48 min/day, 5 days/wk) for 16 or 32 wk. Age-matched, air-exposed mice served as nonsmoking controls. Blood pressure was measured, and cardiac MRI was performed. In vitro vascular ring and isolated heart experiments were performed to measure vascular reactivity and cardiac function. Blood from control and smoking mice was studied for the nitric oxide (NO) decay rate and reactive oxygen species (ROS) generation. With 32 wk of CS exposure, mice had significantly less body weight gain and markedly higher blood pressure. At 32 wk of CS exposure, ACh-induced vasorelaxation was significantly shifted to the right and downward, left ventricular mass was significantly larger along with an increased heart-to-body weight ratio, in vitro cardiac function tended to be impaired with high afterload, white blood cells had significantly higher ROS generation, and the blood NO decay rate was significantly faster. Thus, smoking led to blunted weight gain, hypertension, endothelial dysfunction, leukocyte activation with ROS generation, decreased NO bioavailability, and mild cardiac hypertrophy in mice that were not otherwise predisposed to disease. This mouse model is a useful tool to enable further elucidation of the molecular and cellular mechanisms of smoking-induced cardiovascular diseases.

Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O(2)(•-)), which are key mediators of cellular signalling. In the presence of Ca(2+)/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from l-arginine (l-Arg) by means of electron transfer from NADPH through a flavin containing reductase domain to oxygen bound at the haem of an oxygenase domain, which also contains binding sites for tetrahydrobiopterin (BH(4)) and l-Arg. In the absence of BH(4), NO synthesis is abrogated and instead O(2)(•-) is generated. While NOS dysfunction occurs in diseases with redox stress, BH(4) repletion only partly restores NOS activity and NOS-dependent vasodilation. This suggests that there is an as yet unidentified redox-regulated mechanism controlling NOS function. Protein thiols can undergo S-glutathionylation, a reversible protein modification involved in cellular signalling and adaptation. Under oxidative stress, S-glutathionylation occurs through thiol-disulphide exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl radicals with reduced glutathione. Cysteine residues are critical for the maintenance of eNOS function; we therefore speculated that oxidative stress could alter eNOS activity through S-glutathionylation. Here we show that S-glutathionylation of eNOS reversibly decreases NOS activity with an increase in O(2)(•-) generation primarily from the reductase, in which two highly conserved cysteine residues are identified as sites of S-glutathionylation and found to be critical for redox-regulation of eNOS function. We show that eNOS S-glutathionylation in endothelial cells, with loss of NO and gain of O(2)(•-) generation, is associated with impaired endothelium-dependent vasodilation. In hypertensive vessels, eNOS S-glutathionylation is increased with impaired endothelium-dependent vasodilation that is restored by thiol-specific reducing agents, which reverse this S-glutathionylation. Thus, S-glutathionylation of eNOS is a pivotal switch providing redox regulation of cellular signalling, endothelial function and vascular tone.

Background: Ischemic postconditioning (PoC) is a cardio-protective strategy in which initial reperfusion is interrupted by episodes of ischemia. It is unclear whether PoC can be achieved in the Langendorff perfused rat heart model. We investigated (1) whether postconditioning occurs in Langendorff perfused rat heart and (2) whether there is a gender-specific response to PoC., Materials and Methods: Male/female rat hearts (n = 8/group) were subjected to 30 min of equilibration, 30 min of ischemia, and 120 min of reperfusion (Control). PoC was induced by 6 cycles (PoC 6c10s), 3 cycles (PoC 3c10s), or 2 cycles (PoC 2c10s) of 10 s reperfusion/10 s ischemia. Rate pressure product (RPP) and infarct size were measured. Male rats (n = 7/group) were subjected in vivo to 30 min left coronary ligation followed by 24 h of reperfusion (Control) or PoC 6c10s and 24 h of reperfusion., Results: Recovery of RPP was 18% ± 4% in male Control versus 17% ± 2% for 6c10s, 16% ± 1% for 3c10s, and 15% ± 3% for 2c10s. Female Control hearts recovered 25% ± 3% of their RPP versus 21% ± 2% for 6c10s. Infarct size was 25% ± 3% for male Control versus 26% ± 3% for 6c10s, 30% ± 2% for 3c10s, 28% ± 1% for 2c10s, and 30% ± 2% for female Control versus 29% ± 2% in 6c10s. In vivo infarct size for Control and PoC 6c10s was 44% ± 3% and 28% ± 5%, respectively (P < 0.05)., Conclusions: In the Langendorff perfused rat hearts, none of the PoC protocols improved myocardial tolerance to ischemia reperfusion injury nor decreased infarct size; however, in vivo postconditioning did confer protection. The lack of protection in the isolated hearts was not gender specific., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Ischemic preconditioning (IPC) is a powerful phenomenon that provides potent cardioprotection in mammalian hearts; however, the role of endothelial nitric oxide (NO) synthase (eNOS)-mediated NO in this process remains highly controversial. Questions also remain regarding this pathway as a function of sex and ischemic duration. Therefore, we performed extensive experiments in wild-type (WT) and eNOS knockout (eNOS(-/-)) mice to evaluate whether the infarct-limiting effect of IPC depends on eNOS, ischemic periods, and sex. Classical IPC was induced by three cycles of 5 min of regional coronary ischemia separated by 5 min of reperfusion and was followed by 30 or 60 min of sustained ischemia and 24 h of reperfusion. The control ischemia-reperfusion protocol had 30 or 60 min of ischemia followed by 24 h of reperfusion. Protection was evaluated by measuring the myocardial infarct size as a percentage of the area at risk. The major findings were that regardless of sex, WT mice exhibited robust IPC with significantly smaller myocardial infarction, whereas eNOS(-/-) mice did not. IPC-induced cardiac protection was absent in eNOS(-/-) mice of both Jackson and Harvard origin. In general, female WT mice had smaller infarctions compared with male WT mice. Although prolonged ischemia caused significantly larger infarctions in WT mice of both sexes, they were consistently protected by IPC. Importantly, prolonged myocardial ischemia was associated with increased mortality in eNOS(-/-) mice, and the survival rate was higher in female eNOS(-/-) mice compared with male eNOS(-/-) mice. In conclusion, IPC protects WT mice against in vivo myocardial ischemia-reperfusion injury regardless of sex and ischemic duration, but the deletion of eNOS abolishes the cardioprotective effect of classical IPC.

We consider the impact of saturable nonlinearity and group velocity dispersion on self-induced transparency (SIT) modelocking of quantum cascade lasers (QCLs). We find that self-induced transparency modelocking in QCLs can be obtained in the presence of saturable nonlinearity if the saturable loss or gain is below a critical limit. The limit for the saturable loss is significantly more stringent than the limit for the saturable gain. Stable modelocked pulses are also obtained in the presence of both normal and anomalous group velocity dispersion when its magnitude is below a critical value. The stability limit for the saturable loss becomes less stringent when group velocity dispersion is simultaneously present. However, the stability limit for the saturable gain is not significantly affected. All these limits depend on the ratio of the SIT-induced gain and absorpt n to the linear loss. Realistic values for both the saturable nonlinearity and chromatic dispersion are within the range in which SIT modelocking is predicted to be stable.

The goal of the present study was to assess how reduced SERCA2a expression affects in vivo myocardial ischemia/reperfusion (I/R) injury. We specifically wanted to determine to what extent hearts with reduced SERCA2a levels are susceptible to in vivo I/R injury. Therefore, we examined the effects of different ischemic periods on post-ischemic myocardial injury in wild-type (WT) and SERCA2a heterozygous knockout (SERCA2a(+/-)) mice expressing lower levels of SERCA2a pump in vivo. Following 20-min ischemia and 48-hour reperfusion, SERCA2a(+/-) mice developed significant myocardial infarction (MI) compared to negligible infarction in WT mice (14+/-3% vs. 3+/-1%, P<0.01); whereas following 30-min ischemia, the infarction was significantly larger in SERCA2a(+/-) mice compared to WT mice (49+/-5% vs. 37+/-3%, P<0.05). Further, echocardiographic analysis revealed worsened postischemic contractile function in SERCA2a(+/-) mice compared to WT mice. Thus, these findings demonstrate that maintaining optimal SERCA2a function is critical for myocardial protection from I/R injury and postischemic functional recovery.

The possibility of using the self-induced transparency effect to passively modelock lasers has been discussed since the late 1960s, but has never been observed. It is proposed that quantum cascade lasers are the ideal tool to create this modelocking, due to their rapid recovery times and relatively long coherence times and because it is possible to interleave gain and absorbing layers. Conversely, it is possible to use the self-induced transparency effect to create midinfrared pulses that are less than 100 fs in duration in a semiconductor laser.