Alzheimer’s disease (AD) is a significant health concern worldwide with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells like microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms.

Organ-on-Chip is a game-changing technology born from the convergence of tissue engineering and microfluidic technology. Organ-on-Chip devices (OoCs) are expected to offer effective solutions to persisting problems in drug development and personalized disease treatments. This opinion paper surveys the current landscape in research, development, application and market opportunities for OoCs to help establishing a global and multi-stakeholder OoC ecosystem. Based on a bibliometric study, a market analysis, expert interviews, and panel discussions held at the ORCHID Vision Workshop (Stuttgart, 23 May 2018), we outline presently unmet needs, key challenges, barriers and perspectives of the field, and finally propose recommendations towards the definition of a comprehensive roadmap that could render OoCs realistic models of human (patho)physiology in the near future.

The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, characterization of intestinal disease processes are increasingly gaining more attention as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models they offer more translational value, and many different GOC models have been presented over the past years. Here, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely 1) the biological research questions, 2) chip fabrication and materials, 3) tissue engineering, and 4) the environmental and biochemical cues to add or measure in the GOC. Examples are presented of GOC studies in the two major areas of preclinical intestinal research: 1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and 2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.

The air is not the same as thousands and hundreds of years ago. In the air, suspended particles originate from natural phenomena like dust storms or volcanic activities, as well as anthropogenic pollutants such as fuel engine exhaust and everyday activities at home. The total particles in the air can be classified by sizes, such as PM10, PM2.5 or ultrafine particles. However, there are many other important factors in addition to the particle size, influencing the particle behavior and affecting our health. The surface area, chemical and biological composition, aspect ratio, and the charge are all factors characteristic of particles. OoC microfluidic chips are very useful for the pollutant toxicity measurements on various body tissues. A better understanding of pollutants will help to trace these to the potential sources. The data from the on-the-ground and satellite monitoring can be integrated into models, helping to predict and prevent pollution exposure.

Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested in humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including 3D cell culture models. 3D tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of realistic drug diffusion, paracrine signaling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.

Microfluidic lab-on-chip devices are widely being developed for chemical and biological studies. One of the most commonly used types of these chips is perfusion microwells for culturing multicellular spheroids. The main challenge in such systems is the formation of substantial necrotic and hypoxic zones within the cultured spheroids. Herein, we propose a novel acoustofluidic integrated platform to tackle this bottleneck problem. We show that such an approach enhances cell viability and shrinks necrotic and hypoxic zones in these spheroid-on-a-chip platforms without the need to increase the flow rate, leading to a significant reduction in costly reagents' consumption. Proof-of-concept, designing procedures, and finite element numerical simulation are discussed in details. Also, the effects of acoustic and hydrodynamic parameters on the cultured cells are investigated. The results show that by increasing acoustic boundary displacement amplitude (d0), the spheroid’s proliferating zone enlarges greatly. Moreover, it is shown that by implementing d0=0.5 nm, the required flow rate to maintain the necrotic zone below 13% will be decreased 12 times compared to non-acoustic chips.

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 165 peers in over 30 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability - which is also indicated by an increasing adaptation of the pharmaceutical industry but a lack of complexity can challenge their use as a predictive platform. Self-made systems on the other hand are less robust and standardized but provide the opportunity to develop customized and more complex models which are often needed for human disease modeling. This review serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs.

Pandemics caused by viruses have threatened lives of thousands of people. Viral infection is a complex and diverse process, and substantial studies have been complemented in understanding the biochemical and molecular interactions between viruses and hosts. However, the physical microenvironment where infections implement is often less carefully considered, and the role of mechanobiology in viral infection remains elusive. Mechanobiology focuses on sensation, transduction and response to intracellular and extracellular physical factors by tissues, cells and extracellular matrix. The intracellular cytoskeleton and mechanosensors have been proved to be extensively involved in virus life cycle. Furthermore, innovative methods in vivo and in vitro are being utilized to elucidate how extracellular factors including stiffness, forces and topography in regulating viral infection. Our current review covers how physical factors from different sources coordinate virus infection. We further discuss how this knowledge can be harnessed in future research on cross-fields of mechanobiology and virology.

In this work, an evanescent Bragg grating sensor inscribed in a few-mode planar polymer waveguide was integrated in microchannel structures and characterized with various chemical applications. The planar waveguide and the microchannels consisted of epoxide-based polymers. The Bragg grating structure was post-processed using point-by-point direct inscription technology. By monitoring the central wavelength shift of the reflected Bragg signal, the sensor showed a temperature sensitivity of -47.75 pm/K. Moreover, the functionality of the evanescent field-based measurements is demonstrated with two application examples: refractive index sensing of different aqueous solutions and gas-phase hydrogen concentration detection. For the latter application, the sensor was additionally coated with a functional layer based on palladium nanoparticles. During the refractive index sensing measurement, the sensor achieved a sensitivity of 6.5 nm/RIU from air to 99.9% pure isopropyl alcohol. For the gas-phase hydrogen detection, the coated sensor achieved a reproducible concentration detection up to 4 vol% hydrogen. According to the reported experimental results, the integrated Bragg grating-based waveguide sensor demonstrates high potential for applications based on lab-on-a-chip concept.

Recently, there has been increasing attention toward inhaled nanoparticles (NPs) to develop in-halation therapies for diseases associated with the pulmonary system and investigate the toxic ef-fects of hazardous environmental particles on human lung health. Taking advantage of microfluidic technology for cell culture applications, lung-on-a-chip devices with great potential in replicating the lung air-blood barrier (ABB) have opened new research insights in preclinical pathology and therapeutic studies associated with aerosol NPs. Surprisingly, the air interface in such devices, which makes them tremendously unique among the other common liquid-based cellular mi-crosystems and enables exposure of cultivated cells to the drug/toxic aerosols, has been largely disregarded. Accordingly, there exists a significant research gap in the comprehensive under-standing of the NPs’ dynamics in the lung-on-a-chip devices, which is momentous to control the injection of aerosols to the target area and attain a desired physiochemical efficacy. To address this research gap, a numerical parametric study is presented to provide a deep insight into the dynamic behavior of the airborne NPs in a gas-liquid dual-channel lung-on-a-chip device with a porous membrane separating the channels. A finite element multi-physics model is developed to enable a particle tracing investigation simultaneously in both air and medium phases to replicate the in vivo conditions avoiding laborious and costly experimental trials. The results include the impact of fluid flow as well as geometrical properties on the distribution, deposition, and translocation of the NPs with diameters ranging from 10 nm to 900 nm in the lung-on-a-chip. The obtained results strongly suggest the aerosol injection of NPs instead of the aqueous solution for more efficient deposition on the substrate of the air channel and higher translocation to the media channel. The current study proposes to optimize the affecting parameters to control the injection and delivery of aerosol par-ticles into the lung-on-chip device depending on the objectives of biomedical investigations and provides optimized values for some specific cases. Therefore, this study can assist scientists and researchers in complementing their experimental investigation in future preclinical studies on pulmonary pathology associated with inhaled hazardous and toxic environmental particles, as well as therapeutic studies for developing inhalation drug delivery.

This paper introduces a novel 3D NoC router that combines buffered and bufferless routing with approximate priority comparison when deflecting flits. Our proposal is a modification of an asymmetrical router that is buffered in the z dimension ports and bufferless in the x and y dimension ports. Flits that request output ports in the x and y dimensions are granted or deflected based on approximate, instead of accurate, priority comparison. Experimental results show that the proposed router, besides effectively combining the advantages of both buffered and bufferless routers, it achieves additional performance and area gains due to the reduced logic required for approximate priority comparison in flit deflections. Experimental results using synthetic and realistic traffic show that the proposed router begins to saturate at a sifnificantly higher injection rate than a bufferless router, but at a slightly lower injection rate than when using accurate priority comparison. Furthermore, the proposed router achieves higher clock frequencies and reduced area compared to the simpler permutation network.

Digital microfluidics (DMF) holds great potential for the alleviation of laboratory procedures in assisted reproductive technologies (ARTs). Electrowetting on dielectric (EWOD) provides dynamic culture conditions in vitro that may better mimic the natural embryo microenvironment. Thus far, EWOD microdevices have been proposed for in vitro gamete and embryo handling in mice and for analyzing the human embryo secretome. This article presents the development of the first microfluidic chip utilizing EWOD technology designed for the manipulation of bovine embryos in vitro. The prototype sustains the cell cycles of embryos manipulated individually on the chips during in vitro culture (IVC). Challenges related to the chip fabrication as well as to its application during bovine embryo IVC in accordance with the adapted on-chip protocol are thoroughly discussed, and future directions for DMF in ARTs are indicated.

Microsystems are key enabling technologies, with applications found in almost every industrial field, including in-vitro diagnostic, energy harvesting, automotive, telecommunication, drug screening, etc. Microsystems, such as microsensors and actuators, are typically made up of components below 1000 microns in size that can be manufactured at low-unit cost through mass-production. Yet, the development of microsystems for commercial or educational purposes, has typically been limited to upper income countries due to the initial investment costs associated with the microfabrication equipment and processes. However, recent technological advances have enabled the development of low-cost microfabrication tools. In this paper, we describe a range of low-cost approaches and equipment (below £1000), developed or adapted and implemented in our laboratories. We describe processes including photolithography, micromilling, 3D printing, xurography and screen-printing used for the microfabrication of structural and functional materials. The processes that can be used to shape a range of materials with sub-millimetre feature sizes are demonstrated here in the context of Lab-on-Chips, but they can be adapted for other applications. We anticipate that this paper, which will enable researchers to build a low-cost microfabrication toolbox in a wide range of settings, will spark a new interest in microsystems.

Surface Plasmon Resonance (SPR) based sensors have the advantage of being label-free, enzyme-free and real-time. However, their spreading in multidisciplinary research is still limited and almost confined to prism-coupled devices. Plasmonic gratings, combined with a simple and cost-effective instrumentation, have been poorly developed compared to prism-coupled system mainly due to their lower sensitivity. Here we describe the optimization and signal enhancement of a sensing platform based on phase-interrogation method, which entails the exploitation of a nanostructured sensor. This technique is particularly suitable for integration of the plasmonic sensor in a lab-on-a-chip platform and can be used in a microfluidic circuit to ease the sensing procedures and limit the injected volume. The careful optimization of most suitable experimental parameters by numerical simulations leads to a 30 to 50% enhancement of SPR response, opening new possibilities for applications in the biomedical research field while maintaining the ease and versatility of the configuration.

Since the systematic evolution of ligands by exponential enrichment (SELEX) method was developed, aptamers have made significant contributions as bio-recognition sensors. Microdevice systems allow for low reagent consumption, high-throughput of samples, and disposability. Due to these advantages, there has been an increasing demand to develop microfluidic-based aptasensors for analytical technique applications. This review introduces the principal concepts of aptasensors and then presents some advanced applications of microdevice-based aptasensors on several platforms. Highly sensitive detection techniques such as electrochemical and optical detection have been integrated into lab-on-a-chip devices and researchers have moved towards the goal of establishing point-of-care diagnoses for target analyses.

Screening and early diagnosis of diseases are crucial for a patient's treatment to be successful and to improve their survival rate, especially in cancer. The development of non-invasive analytical methods able to detect biomarkers of pathologies is a critical point to define a successful treat-ment and a good outcome. This study extensively reviews electrochemical methods used for the development of biosensors in liquid biopsy, owing to their ability to provide rapid response, pre-cise detection, and low detection limits. We also discuss new developments in electrochemical biosensors, which can improve the specificity and sensitivity of standard analytical procedures. Electrochemical biosensors demonstrate remarkable sensitivity in detecting minute quantities of analytes, encompassing proteins, nucleic acids, and circulating tumor cells, even within challeng-ing matrices such as urine, serum, blood, and various other body fluids. Among the various de-tection techniques used for the detection of cancer biomarkers, even in the picogram range, volt-ammetric sensors are deeply discussed in this review because of their advantages and technical characteristics. This widespread utilization stems from their ability to facilitate quantitative de-tection of ions and molecules with exceptional precision. The comparison of each electrochemical technique is discussed to provide the selection of appropriate analytical methods.

Considering the actual world economical trends, one of the most important questions is now and in the future: how to reduce power consumption of electronic systems. Since the invention of computers, the electrical energy consumption step by step increased. Now when not only computers, but electric vehicles, robots, automation, and unmanned aerial vehicles play a very important role of our life, the main problem of system designers is how to reduce energy consumption in these systems. But also the existing already working systems must be revised in order to decrease their electric power consumption. The importance of this subject (energy control) shows that a huge number of research publications and survey papers deal with it. Just focusing on the last one or two years (2021 and 2022) the search hit 221000 titles (103000 hits only in 2022). Analyzing all the research areas is almost impossible, but focusing on some important research subjects, where one of the main topic is “energy saving methods” can give an overview about the subject. The paper focuses on the area of industrial robotic systems, electric vehicles, and embedded systems.

An approach employing ultrafast laser hybrid subtractive-additive microfabrication combining ablation, 3D nanolithography and welding is proposed for the realization of Lab-On-Chip (LOC) device. Single amplified Yb:KGW fs-pulsed laser source is shown to be suitable for fabricating microgrooves in glass slabs, polymerization of fine-meshes filter out of hybrid organic-inorganic photopolymer SZ2080 inside them, and, lastly, sealing the whole chip with cover glass into a single monolithic piece. The created microfluidic device proved its particle sorting function by separating 1 μm and 10 μm polystyrene spheres in a mixture. All together, this shows that fs-laser microfabrication technology is a flexible and versatile tool for the manufacturing of mesoscale multi-material LOC devices.

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modelling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues are becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging on chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.

Phosphorus, an essential rare element in aquatic ecosystems, plays a key role in maintaining ecosystem balance. However, an excess of phosphorus will lead to eutrophication and algal pro-liferation. To prevent eutrophication, it is crucial to pretreat and measure the concentration of total phosphorus (TP). Compared with conventional TP pretreatment equipment (autoclave), a lab-on-a-chip detection device fabricated through micro-electromechanical system technology using titania (TiO2) as a photocatalyst is more convenient, efficient, and cost-effective. However, the wide bandgap of TiO2 (3.2 eV) limits the photocatalytic activity. To address this problem, this paper describes the preparation of a TiO2/Au nanocomposite film by electron-beam evaporation and atomic layer deposition, based on the introduction of a gold film and TiO2 on a quartz substrate. The photocatalytic degradation properties of TiO2/Au nanocomposite films with thicknesses of 1, 2, 3, and 4 nm are assessed using rhodamine B as a pollutant. Experimental results demonstrate that the deposition of a gold film with different thicknesses can enhance the photocatalytic degradation efficiency through synergetic reactions in the charge separation process on the surface. The optimal photocatalytic efficiency is achieved when the deposition thickness is 2 nm, and it decreases with further increase in the thickness. When the photocatalytic reaction time is 15 min, the LOC device with a 2-nm-thick gold layer and autoclave exhibit similar TP pretreatment performance. Therefore, the proposed LOC device based on photocatalysis technology can address the limitation of conventional autoclave equipment, such as large volume, long processing time, and high cost, thereby satisfying the growing demand for on-site evaluation.

This study presents the design and implementation of a PLC microprocessor adhering to the IEC-61131-3 standard, executed on a Cyclone-V FPGA using a DE10-NANO development board. Our microprocessor optimizes the central processing unit by streamlining the data path, achieving a remarkable simulated response time of approximately 60 ns, equivalent to three clock cycles at a 50MHz frequency for Boolean operations. To substantiate our approach, we conducted practical experiments utilizing a FESTO conveyor station, employing relays as actuators, and incorporating optical and inductive sensors. The results underscore the feasibility of our proposed approach and serve as practical validation of its efficacy. This work introduces a promising avenue for the development of cost-effective PLCs employing SoC FPGA variants. Additionally, a thorough comparison of execution times with other early reported architectures. Our microprocessor outperforms even well-established PLCs like the S7-312, with substantial reductions in execution times of 94.54% for floating-point operations, 71.42% to 93.33% for word operations, and up to 78.57% for bit operations.

Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here a “3D extensible” microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures- check valve (in), check valve (out), double-check valve (in and out), and on-off valve, were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a “3D extensible” architecture to fulfill the needs of the function integration, the adaptive “world-to-chip” interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect Chlamydia trachomatis automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.

The aim of this study is to provide a detailed strategy for Safe-by-Design (SbD) 3D printed lab-on-a-chip (LOC) device manufacturing, using Fused Filament Fabrication (FFF) technology. At first, the applicability of FFF in lab-on-a-chip device development is briefly discussed. Subsequently, a methodology to categorize, identify and implement SbD measures for FFF is suggested. Furthermore, the most crucial health risks involved in FFF processes are examined, placing the focus on the examination of ultrafine particle (UFP) and Volatile Organic Compound (VOC) emission hazards. Thus, a SbD scheme for lab-on-a-chip manufacturing is provided, while also taking into account process optimization for obtaining satisfactory printed LOC quality. This work can serve as a guideline for the effective application of FFF technology for lab-on-a-chip manufacturing through the safest applicable way, towards a continuous effort to support sustainable development of lab-on-a-chip devices through cost-effective means.

Blade Health Monitoring (BHM) is often necessary in power plants and in aviation to prevent excessive blade vibration and cracks. This article proposes a network of blade tip timing sensors operated in a distributed BHM system. A number of cooperating agents is implemented in smart conditioning units which can autonomously operate in an adverse environment and communicate with other nodes via a serial interface. The project uses special versions of reduced instruction set chips that are able to operate near the hot section of the engine. Due to the limited number of types of microprocessors available in the extended temperature range grading, it was necessary to fully utilize the limited hardware resources and implement preemptive multitasking. For this purpose, a custom operating system and communication protocol were designed. The protocol hosts the middle layer which hides the implementation of the distributed system. The presented architecture ensures the sufficient computational capacity in individual nodes of the network operated in adverse conditions. It is scalable and resistant to transmission errors.

In this work modeling and analysis of an integrated opto-fluidic sensor, with a focus on achievement of single mode optical confinement and continuous flow of micro particles in the microfluidic channel for Lab-on-a Chip (LOC) sensing application is presented. This sensor consists of integrated optical waveguides, microfluidic channel among other integrated optical components. A continuous flow of micro particles in a narrow fluidic channel is achieved by maintaining the two sealed chambers at different temperatures and by maintaining a constant pressure of 1Pa at the centroid of narrow fluidic channel geometry. The analysis of silicon on insulator (SOI) integrated optical waveguide at an infrared wavelength of 1550nm for single mode sensing operation is presented. The optical loss is found to be 0.0005719dB/cm with an effective index of 2.2963. The model presented in this work can be effectively used to detect the nature of micro particles and continuous monitoring of pathological parameters for sensing applications.

Light Detection and Ranging (LiDAR) technology, a cutting-edge advancement in mobile applications, presents a myriad of compelling use cases, including enhancing low-light photography, capturing and sharing 3D images of fascinating objects, and elevating the overall augmented reality (AR) experience. However, its widespread adoption has been hindered by the prohibitive costs and substantial power consumption associated with its implementation. To surmount these obstacles, this paper proposes a low-power, low-cost, SPAD-based system-on-chip (SoC) which packages the microlens arrays (MLA) and incorporates with a light-weight RGB-guided sparse depth imaging completion neural network for 3D LiDAR imaging. The proposed SoC integrates an 8x8 Single-Photon Avalanche Detectors (SPADs) macro pixel array with time-to-digital converters (TDC) and charge pump, fabricated using a 180nm bipolar-CMOS-DMOS (BCD) process. A random MLA-based homogenizing diffuser efficiently transforms Gaussian beams into flat-topped beams with a 45° field of view (FOV), enabling flash projection at the transmitter. To further enhance resolution and broaden application possibilities, a lightweight neural network employing RGB-guided sparse depth complementation is proposed, enabling a substantial expansion of image resolution from 8x8 to quarter video graphics array level (QVGA; 256x256). Experimental results demonstrate the effectiveness and stability of the hardware encompassing the SoC and optical system, as well as the lightweight features and accuracy of the algorithmic neural network. This integrated state-of-the-art hardware-software solution offers a promising and inspiring foundation for developing consumer-level 3D imaging applications.

The lab-on-a-chip concept, enabled by microfluidic technology, promises the integration of multi-ple discrete laboratory techniques into a miniaturised system. Research into microfluidics has generally focused on the development of individual elements of the total system (often with rela-tively limited functionality), without full consideration for integration into a complete fully opti-mised and miniaturised system. Typically, the operation of many of the reported lab-on-a-chip devices is dependent on the support of a laboratory framework. In this paper, a demonstrator platform for routine laboratory analysis is designed and built, which fully integrates a number of technologies into a single device with multiple domains such as fluidics, electronics, pneumatics, hydraulics, and photonics. This facilitates the delivery of breakthroughs in research, by incorpo-rating all physical requirements into a single device. To highlight this proposed approach, this demonstrator microsystem acts as a fully integrated biochemical assay reaction system. The re-sulting design determines enzyme kinetics in an automated process and combines reservoirs, three-dimensional fluidic channels, optical sensing, and electronics in a low-cost, low-power and portable package.

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumor models. The complex tumor microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.

Separation and interpretation of rebellious Circulating Tumor Cells (CTCs) originating from the primary tumor or cancer tissue plays a significant role in diagnostics, cancer progression analyses, suitable medicine exploration, and treatment proficiency examination. Cancer metastasis occurs when CTCs spread throughout the body and invade healthy tissues, leading to new tumors in that area. Although a dramatic rate of deaths begins from spreading CTCs around the body, valuable measures have been made to control their development. However, the first step is separating these harmful cells from the bloodstream and investigating their features. Having examined the characteristics of CTCs as cancer’s main strength, researchers can introduce complementary treatments that can affect cancerous cells without damaging the healthy cells. Therefore, according to their unique characteristics, numerous techniques have been established for continuous and fast separation and sorting of CTCs. Nevertheless, few separators enjoy the efficient performance and appropriate accuracy and can be produced in mass numbers due to the available fabrication equipment. Microfabrication advancements enable separators to combine the advantages of active and passive methods in a small-scale platform for probing individual cells and separation purposes. Reduction in reagents, sample volume, analysis time, and less harmfulness to patients are some of the motivations that encourage researchers to employ microfluidic instruments for CTCs separation from other blood cells over the last two decades. However, microfabrication limitations mean effective separators, and the diagnostic option they provide, are not readily available. Addressing these limitations requires optimizing the design and fabrication of separators such that they are reduced in their size and fabrication cost, while also maintaining high-throughput separating capability. The emergence of the Lab-On-a-Chip (LOC) and then Lab-On-a-CD (LOCD) technologies, having more inherent benefits than conventional microfluidic devices, has created new opportunities and become increasingly widespread in recent years. Evidence suggests that employing single methodologies or integrating approaches without sufficient understanding of potential outcomes is unlikely to result in successful diagnostic results. This paper contributes an extensive review of several separation systems, including fundamental theories and experimental details, and describes detailed operating principles and device performance.

Understanding cell migration is a key step to unravel many physiological phenomena and predict several pathologies, like cancer metastasis. In particular, mechanical confinement has been proved to be a key factor in the cellular migration strategy choice. As our insight in the field improves, new tools are needed in order to empower biologists’ analysis capabilities. In this framework, microfluidic devices have been used to engineer the mechanical stimuli and to investigate cellular migration response in a more controlled way. In this work, we will review the existing technologies employed in the realization of microfluidic cellular migration assays, namely soft lithography of PDMS and hydrogels and femtosecond laser micromachining. We will give an overview of the state of the art of these devices, focusing on the different geometrical configurations that have been exploited to study specific aspects of cellular migration. Our scope is to highlight the advantages and possibilities given by each approach and to envisage the future developments in in-vitro migration studies under mechanical confinement in microfluidic devices.

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

The VisionCube is a 2-unit CubeSat developed in-house, of which the primary mission is aimed at detecting the occurrence of transient luminous events in the upper atmosphere and obtaining corresponding images from the low Earth orbit. An on-board TLE observation system of the VisionCube cubesat is designed and developed by incorporating a photon-sensitive MaPMT and a CMOS image sensor. Also, a distinctive TLE observation software which enables detecting the TLEs and capturing images in a timely manner is devised. By taking into account the limited resources of a small CubeSat in size and power, the on-board observation system is developed employing a system-on-chip design architecture by which both hardware and software can be integrated seamlessly. The purpose of this study is to investigate the functionality of the hardware and the validity of the software algorithm to show the on-board system will operate properly with no human intervention during the space operation. To this end, a ground simulation facility is constructed to emulate the space environment of the TLE occurrence using a set of UV LEDs inside a darkbox. Based on the analysis of the spectral and temporal properties of the TLEs, the randomly generated UV LED pulses are opted for verification scenarios for the TLE observation system. The validation results show that the hardware and the software algorithm of the on-board observation system can effectively detect the TLEs and obtain the images during the on-orbit operation.

Collision avoidance is an important feature in advanced driver-assistance systems, aiming at providing correct, timely and reliable warnings before an imminent collision (objects, vehicles, pedestrians, etc.). A co-simulation framework is proposed in this paper to address the design and evaluation of collision avoidances in a cyber-physical system. The co-simulation framework is supported on the interaction between SCANeR and Matlab/Simulink. From the best of authors’ knowledge, two main contributions are reported in this paper. Firstly, the modelling and simulation of virtual on-chip LIDAR sensors in a cyber-physical system (CPS) considering traffic scenarios is presented. The CPS is designed and implemented in SCANeR. Secondly, an obstacle recognition library with three specific Artificial Intelligence-based methods is also designed based on sensory information database provided by SCANeR. Three methods for collision avoidance detection are considered, i.e.; a multi-layer perceptron neural network, a self-organization map and a support vector machine. Finally, a comparison among these methods for detecting obstacles before different weather conditions is done with very promising results in terms of accuracy. The best results are achieved using the multi-layer perceptron in sunny and fog conditions, the support vector machine in rainy and self-organized map in snowy conditions.

Analytical chemistry applied to medical and diagnostic analysis, recently focused on the development of cost-effective biosensors able to monitor the health status or to assess the level of specific biomarkers that can be indicative for several diseases. The improvement of technologies relating to the possibility of non-invasive sampling of biological fluids, as well as sensors for the detection of analytical signals and the computational capabilities of the systems routinely employed in everyday life (e.g. smartphones, computers, etc.), make the complete integration of self-standing analytical devices more accessible. This review aims to discuss the biosensors that have been proposed in the last 5 years focusing on two principal detecting approaches, optical and electrochemical, which have been employed for quantifying different kind of target analytes reaching detection limits below the clinical sample levels required. These detection principles applied to Point-of-care (POC) devices, have been extensively reported in literature and even the limited examples found on the market are based on these strategies. This work will show the latest innovations considering the integration of optical and electrochemical detection with the most commonly reported analytical platforms for POC applications such as paper-based or wearable and implantable devices.

Conventional diagnostic techniques are based on utilization of analyte sampling, sensing and signalling on separate platforms for detection purposes, that must be evaded and integrated to a single step procedure in point of care (POC) testing devices. Therefore, the trend has been shifted towards utilization of microfluidic platforms for detection of analytes in biochemical, clinical and food technology due to its being expeditious. Microfluidic systems moulded with polymer substances or glass offer specific and sensitive detection of infectious and non-infectious diseases by providing innumerable benefits including less cost, good biological affinity, strong capillary action and simple process of fabrication. In the case of nucleic acid-based nanosensors, there are some challenges that need to be addressed such as cellular lysis, isolation and amplification of nucleic acid required to be accomplished prior to its detection. To avoid utilization of laborious steps for executing these steps, advances have been deployed in this perspective for on-chip sample preparation, amplification and detection which not only improves sensitivity and selectivity but also saves time and resources. This review emphasizes the significance of microfluidic technology for nucleic acid detection of infectious and non-infectious diseases. The implementation of isothermal amplification in concomitance with lateral flow assay greatly increases the binding efficiency of nanoparticles and biomolecules, improves limit of detection and sensitivity. Most importantly deployment of paper-based material made of cellulose reduces the overall cost. Microfluidic technology in nucleic acid testing has been discussed by explicating its applications in different fields. This review concludes with the prospects and proposes future directions in microfluidic based methods in disease diagnosis.

Cancer stem cells remain a challenge to isolate and characterize because of their plastic phenotype. Using a microfluidic lab-on-a-chip based on ultra-high frequency dielectophoresis, we measured the electromagnetic signature of colorectal cancer cells and demonstrated that cancer stem cells show a distinct and lower electromagnetic signature than differentiated cells. The release of extracellular vesicles from tumor cells can drive tumor progression and metastasis development. As extracellular vesicles from cancer stem cells carry more aggressive content, we treated colorectal cancer cells with these vesicles to test whether the lab-on-a-chip can detect a change in phenotype. The electromagnetic signature of treated cells is modified in comparison to untreated cells and sometimes even when no biological change is observed. The lab-on-a-chip provides rapid and relevant result without prior labeling compared to conventional biological approaches. It could be useful in the clinic for early detection of cancer stem cells in the tumor mass and for monitoring the aggressive potential of extracellular vesicles in the bloodstream in order to adapt therapeutic management and prevent relapse.

Soft-Core architecture for Analogue to Digital Converter (ADC) sampling is useful for mixed signal applications. Soft-core architecture for cutting edge odd or even ADC sampling with interface to block RAM memory has not been found. Soft-core architecture as a concept has become popular due to the advantage of customization for different applications as compared to general-core architecture suited for single application. The latest generation of piece wise sampling is odd sampling and was introduced in the second decade of the 20th century. Odd and even order sampling techniques are analogue in nature driven by a tuned (tuned for odd or even) mixer. This paper proposes a third-generation piece wise sampling with soft-core architecture that enables an option to select both odd and even while interfacing to memory mapping. The proposed odd/even has superior SNR performance of 6 dB as compared to existing architecture such as Mod-∆ which recorded worst performance of 18 dB. Advances in soft-core technology have allowed a niche odd/even switching field to be identified and studied, the study has also been extended to include memory architecture.

Recent developments in optical biosensors based on integrated photonic devices are reviewed with a special emphasis on silicon-on-insulator ring resonator. The review is mainly devoted to the following aspects: (1) Principles of sensing mechanism, (2) sensor design, (3) biofunctionalization procedures for specific molecule detection and (4) measurement set-ups and advances in chip-integration. The inherent challenges of implementing photonics-based biosensors to meet specific requirements of applications in medicine, food analysis, and environmental monitoring are discussed.

The UNUSUAL FLORAL ORGANS (UFO) gene is an essential regulatory factor of class B genes and plays a vital role in the process of inflorescence primordial and flower primordial development. We investigated the role of UFO genes in soybean to better understand the development of floral organs through gene cloning, expression analysis, and gene knockout. In situ hybridization demonstrated predominant expression of the GmUFO1 gene in the flower primordium. Phenotypic observation of GmUFO1 knockout mutant lines (Gmufo1) showed obvious alteration in floral organ number and shape, and mosaic organ formation. In contrast, GmUFO2 knockout mutant lines (Gmufo2) showed no obvious difference in floral organs. However, the GmUFO1 and GmUFO2 double knockout lines (Gmufo1ufo2) showed a more severe mutant phenotype than the Gmufo1 lines. Gene expression analysis also showed differences in the expression of major ABC function genes in the knockout lines. Based on the phenotypic and expression analysis, our results suggest the major role of GmUFO1 in the regulation of flower organ formation in soybean and that GmUFO2 does not have any direct effect, but it might have an interaction role with GmUFO1 in the regulation of flower development. In conclusion, the present study identified UFO genes in soybean and improved our understanding of floral development that could be useful for flower design in hybrid soybean breeding.

The investigation of the electromagnetic properties of biological particles in microfluidic platforms may enable wireless monitoring and interaction with functional activity of microorganisms. Of high relevance is the membrane potential as it is one of the most important parameters of living cells. In particular, the complex mechanisms of the cell’s membrane potential are comparable to the dynamics of bacteria membranes, providing a simplified platform for advancing the current techniques and knowledge of general bio-particle dynamics. In this work, we provide a theoretical analysis and experimental results on the microwave detection of bacteria on a microfluidic-based framework for sensing the membrane potential of bacteria. The results enable to further advance the state-of-the-art of electromagnetic bacteria sensing and microfluidic control, and their implication for measuring and interacting with the cell and its membrane potentials, which is of great importance for developing new biotechnological engineered systems and solutions.

Droplet-based microfluidics has revolutionized numerous fields such as biomedical research, pharmaceuticals, drug discovery, food engineering, flow chemistry, and cosmetics. This paper presents a comprehensive study focusing on the detection and characterization of droplets with volumes in the nanoliter range. Leveraging the precise control of minute liquid volumes, we introduced a novel spectroscopic On-Chip microsensor equipped with integrated microfluidic channels for droplet generation, characterization, and sensing, simultaneously. The microsensor, designed with Interdigitated-Ring-Shaped Electrodes (IRSE) and seamlessly integrated with microfluidic channels, offers enhanced capacitance and impedance signal amplitudes, reproducibility, and reliability in droplet analysis. We were able to make analyses of droplets length in the range 1.0-6.0 mm, velocity 0.66-2.51 mm/s, droplet volume 1.07nL-113.46nL. Experimental results demonstrated that the microsensor's has a great performance in terms of droplet size, velocity, and length, with a significant signal amplitude of capacitance and impedance, and real-time detection capabilities, thereby highlighting its potential for facilitating microcapsule reactions and enabling on-site real-time detection for chemical and biosensor analyses on-chip.

The ongoing revolution in Deep Learning is redefining the nature of computing that is driven by the increasing amount of pattern classification and cognitive tasks. Specialized digital hardware for deep learning still holds its predominance due to the flexibility offered by the software implementation and maturity of algorithms. However, it is being increasingly desired that cognitive computing occurs at the edge, i.e. on hand-held devices that are energy constrained, which is energy prohibitive when employing digital von Neumann architectures. Recent explorations in digital neuromorphic hardware have shown promise, but offer low neurosynaptic density needed for scaling to applications such as intelligent cognitive assistants (ICA). Large-scale integration of nanoscale emerging memory devices with Complementary Metal Oxide Semiconductor (CMOS) mixed-signal integrated circuits can herald a new generation of Neuromorphic computers that will transcend the von Neumann bottleneck for cognitive computing tasks. Such hybrid Neuromorphic System-on-a-chip (NeuSoC) architectures promise machine learning capability at chip-scale form factor, and several orders of magnitude improvement in energy efficiency. Practical demonstration of such architectures has been limited as performance of emerging memory devices falls short of the expected behavior from the idealized memristor-based analog synapses, or weights, and novel machine learning algorithms are needed to take advantage of the device behavior. In this work, we review the challenges involved and present a pathway to realize ultra-low-power mixed-signal NeuSoC, from device arrays and circuits to spike-based deep learning algorithms, with ‘brain-like’ energy-efficiency.

The relative paucity of donor livers suitable for transplantation has sparked innovations to preserve and recondition organs to expand the pool of transplantable organs. Currently, machine perfusion techniques have led to the improvement of the quality of marginal livers and to prolonged cold ischemia time and allowed for the prediction of graft function through analysis of the organ during perfusion, improving the rate of organ use. In the future, the implementation of organ modulation might expand the scope of machine perfusion beyond its current usage. The aim of this review was to provide an overview of the current clinical use of machine perfusion devices in liver transplantation and provide a perspective for future clinical use, including therapeutic interventions in perfused donor liver grafts.

Why do the eyes remain comparatively large whereas the cornea is reduced in most troglobiont mysids? Are there any important organ size-dependent functions served by non-visual eye rudiments? This issue was approached by measuring eye structures in five troglobiont species of Mysida and two Stygiomysida compared with 14 troglophile and 49 trogloxene Mysida species. The Organ of Bellonci (OB) was found in all Mysida and as first records also in Stygiomysida. The length of OBs increased with individual body length and eye length in four examined species: from postnauplioid larvae to adult stage in a troglophile and a trogloxene mysid species examined; and from juveniles to adults in a troglobiont mysid and a troglobiont stygiomysid. At the interspecific level, eye length was on average 26% shorter at a given body length while the OB was 40% longer at a given body length and 54% longer at a given eye length, respectively, in adult troglobionts compared with trogloxene mysids. The OB is clearly proliferating while the cornea is reduced in troglobionts. This points to sensory functions (possibly together with other functions). The sensory pore organ was found in all 15 Mysida species whose eyes were mounted on slides, and a first record of this organ was also found in Stygiomysida.

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell culture due to various limitations of in vivo testing. Unfortunately, in vitro cell culture fails to provide an accurate microenvironment, and in vivo cell culture is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The key component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

To increase the network computer and mobile telephone capacity one needs a laser to carry information instead of electrons. Since the laser is very fast compared to electrons, one expects information to be transmitted very fast through the network (internet). This requires searching for chips that act as capacitors, inductors, or evens as resistors this work shows that the laser traveling beam diminished as the frequency reciprocal thus acts as a capacitor or diminished as frequency thus acts as an inductor and sometimes diminished with the concentration of carriers thus act as a resistor for magnetic materials with strength that cancels the friction force when the laser frequency is equal nearly to the atoms natural frequency the material act as an inductor. Then frictional force is dominant with high mobility dielectric, the material acts as a capacitor. However, it acts as a conductor for negligible friction and natural frequency.

Liquid manipulation by photoisomerization attracts recent attentions as a new active droplet control method for micro-chemical analysis. Such a non-inverse manipulation can be realized by a use of solution liquid of surfactant that exhibits the \emph{cis}-\emph{trans} isomerization triggered by light irradiation with a specific wavelength such as ultraviolet light. Since the isomerization is accompanied by changes in fluid properties, a light irradiation on one of liquid-air interfaces of a liquid column in a tube would generate differences in the wettability accompanied between the both sides of the finite liquid column. Although this technique has been demonstrated experimentally by Muto et al. (\emph{Euro.~Phys.~J.~Special Topics}, {\bf 226}, 2016, 1199--1205), its dynamics and developments of each isomer distribution are not understood. In order to reveal the liquid-column migration phenomenon, we have performed numerical simulations of air-liquid two-phase flows and its scalar transport of the isomer, using the Volume-of-Fluid method in conjunction with the Continuum-Surface-Force model and Continuous-Species-Transfer method. We validated present results by comparison with experimental result in terms of the migration distance of the liquid column. We confirmed a termination of the liquid-column migration occurs when the \emph{cis} isomer distribution reaches the non-irradiated region. The migration speed was less dependent on the liquid-column length and was proportional to the tube diameter.

Systemic sclerosis (SSc) is a progressive autoimmune disorder that mainly affects the skin. There are other clinical manifestations as renal, pulmonary, cardiovascular, and gastrointestinal tract involvements. Based on the skin involvement there are two subtypes of SSc, as limited cutaneous SSc (lSSc) which involves the acral part of the body and diffuse cutaneous SSc (dSSc) resulting in significant skin thickening of the body. The lSSc has usually moderate internal organ manifestations, except for the late-onset pulmonary arterial hypertension (PAH) mainly appearing in this form. In dSSc the severity of the organ manifestations or failure is more intensive such as scleroderma renal crisis (RSC), interstitial lung disease (ILD), myocardial fibrosis, and chronic gastrointestinal dysmotility with consequent malabsorption

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

Many centers worldwide raised the concern that immunocompromised patients for solid organ transplantation may be at high risk of developing a severe respiratory disease by COVID-19. Currently, there are no specific data on the COVID-19 in patients with generalized immunosuppression and transplantation.In this narrative review, we reported the main data of COVID-19 in patients with solid organ transplantation presented in the literature. The aim is to elaborate a strategy for tailored management, from diagnosis to therapy.The management of adult patients with solid organ transplantation and COVID-19 is a challenge for the clinicians. There is a lack of data in the literature, but three key-points are crucial: in the “pandemic era,” consider the symptomatic patient as positive for COVID-19 until proven otherwise; adjust/stop immunosuppressive agents; protect graft function with adequate route and dose administration of glucocorticoid and supportive measures. For pediatric patients, data are scarce. It is unclear if immunosuppression in patients with solid organ transplantation alters the predisposition to acquiring COVID-19 or if the disease implications are modified for better or for worse. Further studies are needed.

Background: Immunosuppressant blood levels should be measured at regular periods in order to keep them within the therapeutic index. Although LC-MS/MS is preferred as a reliable method, some molecules like radiopaque agents in blood matrix may lead to false results. The aim of this study is to investigate the effect of seven different radiopaque agents on immunosuppressant drugs. Methods: Seven different radiopaque agents were added into control materials containing tacrolimus, everolimus, sirolimus and cyclosporine A drugs. Measurements were performed by LC-MS/MS instrument. The amount of deviations from target values were calculated. Results: Immunosuppressant blood levels significantly changed after the administration of radiopaque agents. Seven different radiopaque products led to false negative results in tacrolimus and cyclosporine A levels at a rate of 19.77% to 44.45%. The smallest deviations were seen in everolimus levels with administration of RM6 (gadodiamide) and in sirolimus levels with RM1 (gadobutrol) at rates of 4.04% and 2.11%, respectively. The highest deviations were observed with RM3 (iohexol) administration in everolimus and sirolimus levels at rates of 153.72% and 171.41%, respectively. Conclusions: False immunosuppressant results associated with radiopaque agents may result in organ rejection. Preferring radiopaque agents that cause the least interference risk is important to reduce the organ rejection risk. However, the least risky method is to obtain samples for drug levels before contrast-enhanced imaging.

Nanoparticles (NPs) are widely used in diverse disciplines, including biology, medicine science. The central question that need to be answered is whether NPs have toxic effects on biological cells and molecules or are they safe. The safety of NPs including targeted drug delivery is critical and so is their toxicity in the environment. In recent years, in vitro and in vivo research on animals has generated abundant information about the toxicity of NPs. However, due to varying laboratory conditions, the comparison of the results from ensuing studies is somewhat unreliable. It should be noted that, depending on the type of production, NPs can enter the body through inhalation, skin and via digestive routes. Due to the diversity of NPs and their properties, there is paucity of accurate information on their toxicological effects; particle size, shape, surface area and the chemical levels are considered as key factors in creating health and toxicological effects. Consequently, there is a need for reliable information about their effects on various organs so as to deal with NPs effectively and their impact on health and the environment. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

The pleiotropic biochemical and antioxidant functions of Vitamin C (Vit C) have recently sparked interest in its application in intensive care. Vit C protects important organ systems such as the cardiovascular, neurologic and renal system during inflammation and oxidative stress. Vit C also influences the systems of coagulation and inflammation and its application might prevent the development of organ damage. The current evidence of Vit C’s effect on the pathophysiological reactions during various acute stress events, such as sepsis, shock, trauma, burn and ischemia-reperfusion injury imposes the question, if the application of Vit C might be especially beneficial for cardiac surgery patients, who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of Vit C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between Vit C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence regarding the administration of Vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage and most the appropriate application strategy.

Gravity played an important role in the development of life on earth. The effect of gravity on a living organisms can be investigated by controlling the magnitude of gravity. Most reduced gravity experiments are conducted on the lower earth orbit (LEO) in the International Space Station (ISS). However, running experiments in ISS face challenges such as high cost, extreme condition, lack of direct accessibility, and long waiting period. Therefore, researchers have developed various ground-based devices and methods to perform reduced gravity experiments. However, the search for life outside the earth requires more intensive research. Advancements in conventional methods and the development of new tools are required for this purpose. The advantages of Lab-on-a-Chip (LOC) devices make them an attractive option for simulating microgravity. This paper briefly reviews the advancement of LOC technologies for simulating microgravity in a earth-based laboratory.

Despite accumulating evidence for the pro-apoptotic role for X-linked inhibitor of apoptosis-associated factor 1 (XAF1), its involvement in endoplasmic reticulum (ER) stress response remains undefined. Here, we report that XAF1 enhances cell sensitivity to ER stress and acts as a switch in unfolded protein response (UPR)-mediated cell-fate decisions favoring apoptosis over adaptive autophagy. XAF1 interacts with and destabilizes ER stress sensor GRP78 through the assembly of zinc finger protein 313-mediated destruction complex. Moreover, XAF1 gene transcription is activated by ER stress through PERK-Nrf2 signaling to direct an adaptive to apoptotic switch of stress response by blocking C-terminus of Hsc70-interacting protein (CHIP)-mediated K63-linked ubiquitination and subsequent phosphorylation of inositol-required enzyme-1α (IRE1α). In tumor xenograft assays, XAF1-/- tumors display substantially lower regression compared to XAF1+/+ tumors in response to cytotoxic dose of ER stress inducer. XAF1 and GRP78 expression show an inverse correlation in human cancer cell lines and primary breast carcinomas. Collectively this study uncovers an important role for XAF1 as a linchpin to govern the sensitivity to ER stress and the outcomes of UPR signaling, illuminating the mechanistic consequence of XAF1 inactivation in tumorigenesis.

We report a small footprint cost-effective isothermal rapid DNA amplification system, with integrated microfluidics for automated sample analysis and detection of SARS-CoV-2 in human and environmental samples. Our system measures low-level fluorescent signal in real-time during amplification, while maintaining the desired assay temperature, on a low power, portable system footprint. A unique soft microfluidic chip design was implemented to mitigate thermocapillary effects and facilitate optical alignment for automated image capture and signal analysis. The system-on-board prototype coupled with the LAMP primers designed by BioCoS, is sensitive enough to detect viral loads of SARS-CoV-2 in a broad concentration range corresponding to a threshold cycle range of 16 to 39. Clinical specimens were tested at Kingston Health Sciences using a clinically validated PCR assay and variants were determined using whole genome sequencing.

Under the main features required on portable devices in electrochemical instrumentation is to have a small size, low power consumption, economically affordable, and precision in the measurements. This paper describes the development of a programmable Embedded Potentiostat System (EPS) capable of performing electrochemical sensing over system-on-a-chip platforms. Furthermore, the study explains a circuit design and develops some validation of the entire system. The hardware validation is performed by electrochemical experiments such as Double Step Chronoamperometry (DSC), Linear Sweep Voltammetry (LSV) and Cyclic Voltammetry (CV); moreover, a comparison of the experimental signals between a commercial potentiostat and the EPS was done by analysis of errors on the response signal. Results illustrate that the EPS is capable of handling currents in the range of absolute values of 86.44 to 3000 nA, and having control voltages in the range of ± 2 V. The device can support from 50 to 2000 samples per second. The EPS capabilities were compared with other compact potentiostats. The programmable EPS is an original approach which hugely reduces the hardware complexity and leads the way to create new applications for Point-of-Care or industrial developments with a reusable full electronics module.

Hip replacement has significantly improved the quality of life of patients with symptomatic hip osteoarthritis. Metal-on-metal (MoM) bearings have been used with conventional total hip re-placement (THR) for several decades with promising results from early applications. Wear and corrosion of these implants may lead to a release of metal products into surrounding tissue and body fluids. From the 1980s onwards, the search for increasingly better coupling materials with low levels of wear led to the rise of hard-on-hard couplings such as ceramic-on-ceramic (CoC). The latter is currently the coupling with the longest known duration and with a wear rate close to zero. MoM coupling has been for a long time the most significative alternative, but systemic and local complications linked to the release of chromium and cobalt ions, determine the withdrawn from the market. One other alternative proposed over the time has been Ceramic-on-Metal (CoM) bearing. Preliminary results have been described as favourable, but due to the failures of metal on metal it has been withdrawn from the market, without causing significant clinical complications. In this narrative review, we analysed risks and benefits associated with the implantation of hybrid hard-on-hard bearings, such as CoM.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

Background: Chronic kidney disease (CKD) is a common complication of non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD), increased serum creatinine ≥50%, renal replacement therapy (RRT), and death in pre-transplant, peri-transplant and post-transplant period. Results: 74 patients were studied (7 heart transplant, 34 liver transplants, and 33 lung transplant). Patients who were not followed-up by nephrology in the pre-transplant (p<0.027), peri-transplant (p<0.046), and the longest time until outpatient clinic follow-up (HR 1,032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred higher risk than liver or hear transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxic and the number of hospital admissions were significantly associated to present a creatinine increase ≥50% and develop ESKD. Conclusion: An early follow-up by the nephrology department was associated with a decrease in the worsening of renal function.

The orchid market is a dynamic horticultural business in which novelty and beauty command high prices. The development of miniature to large and showy flowers, in addition to fragrance, is mainly of interest. Overall organ size might be modified by doubling the chromosome number, which can be accomplished by careful study of meiotic chromosome disjunction in hybrids or species. Meiosis is the process in which diploid (2n) pollen mother cells recombine their DNA sequences and then undergo two rounds of division to give rise to four haploid (n) cells called sporads. Thus, by interfering in chromosome segregation, one can induce the development of diploid recombinant sporads called dyads. These dyads may be used for breeding polyploid progenies with enhanced fertility and large flower size. This review gives an overview of developments in orchid breeding placed in the large context of ploidy breeding in higher plants to facilitate innovation

Granulomatosis with polyangiitis (GPA) is an autoimmune disease which is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that frequently affects the lungs and kidneys. However, GPA limited to a single organ has also been reported. A 73-year-old man was admitted for back pain and fever. We detected elevated levels of inflammatory markers and myeloperoxidase-ANCA. Magnetic resonance imaging indicated diffuse inflammation of the back and psoas muscles. Histology showed degenerated muscle fibers and granulomatosis vasculitis with mixed lymphoplasma cell infiltration. High-dose methylprednisolone therapy improved his symptoms. A final diagnosis of GPA limited to the muscles was made.

Ultrafast chip nanocalorimetry opens up remarkable possibilities in materials science by allowing samples to be cooled and heated at extremely high rates. Due to heat transfer limitations, controlled ultrafast cooling and heating can only be achieved for tiny samples in calorimeters with a micron-thick membrane. Even if ultrafast heating can be controlled under quasi-adiabatic conditions, ultrafast controlled cooling can be performed if the calorimetric cell is located in a heat-conducting gas. It was found that the maximum possible cooling rate increases as 1/r0 with decreasing radius r0 of the hot zone of the membrane. The possibility of increasing the maximum cooling rate with decreasing r0 was successfully implemented in many experiments. In this regard, it is interesting to answer the question: what is the maximum possible cooling rate in such experiments if r0 tends to zero? Indeed, on submicron scales, the mean free path of gas molecules lmfp becomes comparable to r0, and the temperature jump that exists at the membrane/gas interface becomes significant. Considering the limitation associated with thermal resistance at the membrane/gas interface and considering the transfer of heat through the membrane, we show that the controlled cooling rate can reach billions of K/s, up to 1010 K/s.

We previously reported how the loss of CHIP expression (Carboxyl terminus of Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac dysfunction, accompanied by a failure to maintain ATP levels in the face of increased energy demand. In this study, we analyzed the cardiac metabolome after seven days of pressure overload and found an increase in long- and medium-chain fatty acid metabolites in wild-type hearts, a response that was attenuated in mice that lack expression of CHIP (CHIP^-/-). These findings suggest that CHIP may play an essential role in regulating oxidative metabolism, pathways that are regulated in part by the nuclear receptor PPARα (Peroxisome Proliferator-Activated Receptor alpha). Next, we challenged CHIP^-/- mice with the PPARα agonist, fenofibrate. Surprisingly, treating CHIP^-/- mice with fenofibrate for five weeks under non-pressure overload conditions resulted in a loss of skeletal muscle mass and a marked increase in cardiac fibrosis, accompanied by a decrease in cardiac function. Isolated CHIP^-/- cardiac fibroblasts treated with fenofibrate did not increase synthesis of collagen or TGFβ, suggesting that the fibrosis observed in CHIP^-/- hearts likely depends on signaling from other cell types or circulating factors. In conclusion, in the absence of functional CHIP expression, fenofibrate results in unexpected cardiac pathologies. These findings are particularly relevant to patients harboring loss-of-function mutations in CHIP and are consistent with a prominent role for CHIP in regulating cardiac metabolism.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level CMOS-chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

Background: The liver has emerged as a frequent transplanted organ which can transmit T. gondii between seropositive donors and seronegative recipients. Associated with the immunosuppressive therapy of recipients, the presence of cysts in donor livers elevate the risk of severe toxoplasmosis in recipients. Objectives: The objective of the study was to verify the frequencies of positive serology in liver graft donors and their respective recipients, as well as to verify whether their clinical signs presented post-transplant are associated with the serological status of recipients. Patients and methods: All data on liver transplant recipients from 2008 to 2018 were obtained from the MVPeP electronic medical records of the Liver Transplant Service of FUNFARME/FAMERP. IgM and IgG anti-T. gondii antibody serology was investigated by chemiluminescence. According to the serological profile, four groups of recipients were assessed (G1: IgG-/IgM-; G2: IgG+/IgM-; G3: IgG+/IgM+, G4: IgG-/IgM+). Results: The numbers of recipients according to the serological profile groups were: G1: 20 (41.7%), G2: 26 (54.1%; G3: 2 (4.2%). No cases were found for G4. Post-transplant clinical manifestations such as fever without defined cause, lung nodules, headache, hepatosplenomegaly, encephalopathy and hepatitis (A, B and C) were reported in all groups. Conclusions: This study demonstrates that there is a high prevalence of T. gondii infection in liver recipients and, therefore, screening should be intensified. Furthermore, a high incidence of co-infection with hepatitis A was identified especially in patients who died in the post-transplant period.

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

Background and objectivesː Physical examination is the predominant method for evaluating pelvic floor defects. Magnetic Resonance Imaging (MRI) is a radiological technique useful to identify the underlying defects of pelvic floor structures that require surgery. The primary aim was to find correspondence between the clinical and radiological staging of pelvic organ prolapse (POP) before and after vaginal surgery. A secondary endpoint was to investigate, through clinical and MRI findings if surgery influences continence mechanisms. Finally, we reported changes in the quality of life in women who underwent surgery for prolapse. Materials and methodsː Twenty-five women with prolapse stage ≥ 2 POP-Q were recruited in this prospective study. They underwent preoperative clinical examination, MRI at rest and under the Valsalva maneuver, and quality of life questionnaires. Three months after vaginal surgery they repeated clinical and radiological evaluation. Resultsː Twenty women completed the study. Both clinical and MRI evaluations showed an improvement in prolapse and symptoms after surgery. There were some discrepancies between clinical and radiological staging. MRI parameters did not show differences between pre and postoperative at rest; under the Valsalva maneuver instead, the measurements changed after surgery. Continence was not worsening by the widening of the vesicourethral angle. Patients reported improvement in quality of life. Conclusionsː MRI is an accurate and objective method to define the stage of prolapse but the clinical evaluation alone is sufficient to stage prolapse before surgery and evaluate the result at follow-up. It is an accurate method to visualize some pelvic structures that can be compromised because of pelvic organ prolapse. MRI showed that vaginal surgery doesn’t affect continence mechanisms.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 hours after admission. Forty-five (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 hours after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01. Animals were cannulated, then recovered for 5-7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels that coincided with severity of tissue damage and mortality. CX-01 inhibited systemic HMGB1 release, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.

In plants, water flows are the major driving force behind the growth and play a crucial role in the life cycle. To study hydrodynamics, methods based on tracking small particles inside water flows occupy a special place. Due to these tools, it is possible to get information about the dynamics of the spatial distribution of the fluxes characteristics. In this paper, using contrast-enhanced MRI, we have shown that gadolinium chelate, used as an MRI contrast agent, marks the structural characteristics of xylem bundles of maize stem nodes and internodes. Supplementing MRI data, a high-precision visualization of xylem vessels by laser scanning microscopy was used to reveal structural and dimensional characteristics of the stem vascular system. In addition, we proposed the concept of using the prototype "Y-type xylem vascular bundles" as a model of the elementary connection of vessels within the vascular system. A Reynolds number can match the microchannel model with the real xylem vessels.

The illegal use of explosives by terrorists and other criminals is an increasing issue in public spaces, such as airports, railway stations, highways, sports arenas, theaters, and other large buildings. Security in these environments can be achieved by a set of different means, including the installation of scanners and other analytical devices to detect ultra-small traces of explosives in a very short time-frame to be able to take action as early as possible to prevent the detonation of such devices. Unfortunately, an ideal explosive detection system still does not exist, which means that a compromise is needed in practice. Most detection devices lack the extreme analytical sensitivity, which is nevertheless necessary due to the low vapor pressure of nearly all explosives. In addition, the rate of false positives needs to be virtually zero, which is also very difficult to achieve. Here we present an immunosensor system based on kinetic competition, which is known to be very fast and may even overcome affinity limitation, which impairs the performance of many traditional competitive assays. This immunosensor consists of a monolithic glass column with a vast excess of immobilized hapten, which traps the fluorescently labeled antibody as long as no explosive is present. In the case of TNT occurring, some binding sites of the antibody will be blocked, which leads to an immediate breakthrough of the labeled protein, detectable by highly sensitive laser-induced fluorescence with the help of a Peltier-cooled CMOS camera. Liquid handling is performed with high-precision syringe pumps and chip-based mixing-devices and flow-cells. The system achieved limits of detection of 1 pM (1 ppt) of the fluorescent label and around 100 pM (20 ppt) of the explosive 2,4,6-trinitrotoluene (TNT). The total assay time is less than 8 min. A cross-reactivity test with 5000 pM solutions showed no signal by PETN, RDX, and HMX. This immunosensor belongs to the most sensitive and fastest detectors for TNT with no significant cross-reactivity by non-related compounds.

NF-B signalling is crucial for cellular responses to inflammation but has also been associated with the hypoxia response. NF-B and HIF transcription factors possess an intense molecular crosstalk. Although it is known that HIF-1beta modulates NF-kappaB transcriptional response, very little is understood regarding how HIF-1beta contributes to NF-kappaB signalling. Here, we demonstrate that HIF-1beta is required for full NF-kappaB activation in cells following canonical and non-canonical stimuli. We found that HIF-1beta specifically controls TRAF6 expression in human cells but also in Drosophila melanogaster. HIF-1beta binds to the TRAF6 gene and controls its expression independently of HIF-1alpha. Furthermore, exogenous TRAF6 expression is able to rescue all of the cellular phenotypes observed in the absence of HIF-1beta. These results indicate that HIF-1beta is an important regulator of NF-kappaB with consequences for homeostasis and human disease.

This study compared the use of chip and slash to minimize the loss of sediment on newly constructed forest road slopes and investigated the annual amount of sediment loss on bare forest road slopes. A runoff block (sample field) was established for each of the four designated test sites (two cutslopes and two fillslopes). Each block had three runoff plots. One of the runoff plots was left empty for the control (CNT), while chip (C) and slash (S), respectively, were deposited in the other two. A total of 108 water samples were taken from the test sites and the amount of their suspended sediment calculated in the laboratory. As a result of this study, it was determined that the amount of soil loss in the control plots was about 1.26 times higher than in the slash plots and 2.21 times higher than in the chip plots. According to the results of variance analysis on the amounts of sediment, a statistically significant difference was found between the suspended sediment quantities transported on the road slopes (P <0.05). However, no statistically significant difference between the suspended sediment quantities transported in the plots and the other variables of aspect, gradient or road slope was revealed by the t-test (P >0.05).

Background: Exclusively breastfeeding your newborn while in the hospital is imperative for suc-cessful breastfeeding at home. This study will investigate if having a nurse on-site during rooming-in can enhance the proportion of exclusive breastfeeding. Methods: We carried out a prospective cohort study to assess exclusive breastfeeding in the first three months of life among two Neona-tology Units in Southern Italy with different hospital settings. The Ente Ecclesiastico Miulli of Ac-quaviva delle Fonti had on-site nurses available 24/7 (on-site group), while the Policlinico of Bari had nurses available on call 24/7 from the Neonatology Unit (on-call group). Results: Between January 3rd and March 31st, 2018, a total of 564 sets of mothers and babies were admitted - 299 on-site and 265 on-call. The exclusive breastfeeding rate for the entire group was 76.4% at 90 days, demonstrating the positive impact of rooming-in and nursing, regardless of the setting. Infants delivered via ce-sarean section in the on-site group demonstrated higher rates of exclusive breastfeeding at both 30 and 90 days of life. Conclusions: Our research indicates that having a nurse available at all times is crucial for promptly identifying any problems with breastfeeding. We highly suggest having an on-site nurse present during rooming-in for mothers who have had a caesarean delivery. This nurse should continuously promote exclusive breastfeeding until the baby is three months old.

End-stage heart failure (ESHF) leads to hypoperfusion and edema formation in the whole body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. Our aim was to explore the relationship between the clinical outcome of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at transplantation after opening the pericardial sac. The clinical data and the interleukin, adipokine and lipoprotein levels in the pericardial fluid of twenty recipients were investigated. Outcome variables included primer graft dysfunction (PGD), need for posttransplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥ 2R rejection and mortality. Recipient risk scores were also investigated. Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 [IQR: 5.55-6.62]; versus 7.54 [IQR=6.71-10.44]; p = 0.029). Higher ApoCII levels (median: 14.91 [IQR: 11.55-21.30] versus 10.31 [IQR=10.02-13.07]; p = 0.042) and ApoCIII levels (median: 60.32 [IQR: 43.00-81.66] versus 22.84 [IQR=15.84-33.39]; p=0.005) were found in patients (n=5) who died in the first 5 years after HTX. In patients who had rejection (n=4) in the first month after transplantation, the levels of adiponectin (median: 74.48 [IQR: 35.51-131.70] versus 29.96 [IQR: 19.86-42.28]; p=0.039), ApoCII (median: 20.11 [IQR: 13.06-23.54] versus 10.32 [IQR: 10.02-12.84]; p=0.007) and ApoCIII (median: 70.97 [IQR: 34.72-82.22] versus 26.33 [IQR: 17.18-40.17; p=0.029) were higher than those in the nonrejection group. Moreover, the pericardial thyroxine (T4) levels (median: 3.96 [IQR: 3.49-4.46] versus 4.69 [IQR: 4.23-5.77]; p=0.022) were lower in patients with rejection than in patients who did not develop rejection. Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecast of early and late complications.

Personality changes have been reported to occur following organ transplantation, and most commonly among heart transplant recipients. We set out to examine whether personality changes do occur following transplantation, and specifically, what types of changes occur among heart transplant recipients compared to other organ recipients. A cross-sectional study was conducted in 2022, in which 47 participants (23 heart recipients and 24 other organ recipients) completed an online survey. In this study, 89% of all transplant recipients reported experiencing personality changes after receiving their organ transplant, which was similar for heart and other organ recipients. With the exception of physical attributes, the types of personality changes reported were similar between the two groups. These finding indicate that heart transplant recipients are not unique in their reported experience of personality changes following organ transplantation. Further studies are needed to deepen our understanding of what causes these personality changes following organ transplantation.

Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

Heavy load carrying of water, firewood, and sand/stones is a ubiquitous activity for women living in developing countries. Although the intra-abdominal pressure associated with heavy load carrying is hypothesized to increase the risk of pelvic organ prolapse (POP) among women, relevant epidemiologic data are lacking. We conducted a comparative study involving two exploratory cross-sectional studies among convenience samples of women carrying heavy loads, with different characteristics: (1) as part of their activities for daily living, in Shinyanga region, Tanzania; and (2) working as sand miners in Pokhara, Nepal. Women were categorized has having “low” or “high” load-carrying exposures based on the measured weights of the loads being carried at the time of the survey, as well as on self-reported duration and frequency of load carrying. A summary score for lower abdominal discomfort suggestive of POP was generated using questions from the Pelvic Organ Prolapse Distress Inventory (POPDI-6). Women with higher load carrying exposures had on average higher discomfort scores in both Tanzania (adjusted prevalence difference (PDa)=3.7; 95% CI: -3.8-11.3; p=0.33) and Nepal (PDa=9.3; 95% CI: -4.9-23.6; p=0.18). We identified trends suggestive of an association between increasing heavy load carrying exposures and symptoms of lower abdominal discomfort. Our findings underscore the need for larger epidemiologic studies of the potential adverse reproductive health effects of heavy load carrying activities on women in developing countries.

Objectives: To demonstrate the efficacy of Gemtuzumab ozogamicin in refractory AML patients with organ dysfunctions and poor performance status. Three refractory AML patients with are described. One of them was pretreated by intensive chemotherapy, two other patients progressed during Azacitidine treatment. WHO performance status III . Two patients had respiratory failure grade 2, the other one suffered from acute kidney insufficiency. Two patients were highly febrile with elevated CRP level. Gemtuzumab ozogamicin administration was performed in three patients followed by further switch to Gemtuzumab ozogamicin + Azacitidine or “7+3” treatment. Results: Gemtuzumab ozogamicin administration resulted in abrupt fever cessation in two febrile patients simultaneously with CRP level decrease and fast gradual resolution of respiratory failure. Recovery of kidney function was noticed in patient with renal insufficiency. WHO performance status have elevated in all three patients. No adverse effects grade II-III were noticed. Further treatment made two patients eligible for intensive chemotherapy, one patient was transplanted, patient with kidney failure obtained complete remission. Conclusions: Gemtuzumab ozogamicin therapy appeared to be safe and highly efficacious in relapsed/refractory AML patients with organ dysfunctions and poor performance status.

Cisplatin induces early-onset ototoxicity, resulting in hearing loss. The exact mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase(RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in animal models. Sprague–Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were was measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H-E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. H-E stains outlined necroptotic changes in the organ of Cortis (OCs) and spiral ganglion neurons (SGNs). Additionally, immunohistochemistry and western blot analysis showed overexpression of RIP3 in the OCs and SGNs that were treated with cisplatin. These results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.

Pin-on-plate and pin-on-disk wear tests are typically used for assessing the wear behavior of a given material coupling. Such a behavior is frequently described by a wear coefficient k, which is estimated, according to the Archard’s law, as the ratio between the measured wear volume V and the product of the applied normal force F and the sliding distance s, i.e. k=V/(F s). This study demonstrates that such a relationship is correct for pin-on-plate but not for pin-on-disk, particularly for flat-ended pins. Both analytical and finite element models of the two tests were developed, considering three different distances pin-disk axis. As results, wear volumes, pressure and wear depth maps were examined and compared for the same sliding distance. Though this study is focused only on the initial transient part of the wear tests, some interesting aspects arose: i) rotational effect in pin-on-disk tests affects k estimation, especially when the pin is near to the disk axis; ii) a simple analytical function is defined to correct the wear volume estimation for pin-on-disk tests; iii) due to the different sliding distances of contact points in pin-on-disk tests, pressure redistribution occurs with higher values on the inner side (closer to disk axis); the opposite trend is observed in wear depth maps. From a computational point of view, the pin-on-disk problem, only apparently simple, required very small time increments to correctly describe the circular trajectories of points, with high computational costs. Numerical strategies are currently under investigation to extend the study to the steady state phase of both tests.

The aim of this paper is to establish a valid procedure for better understanding all the phenomena associated with the high-speed machining of Glass Fibre Reinforced Plastic (GFRP) composites. Both rectangular and circular specimens were machined at high speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface, were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations are found between the variations of the cutting forces' signals and the trends of the roughness and the morphology of the machined surface.

Graphene quality for use in biosensors was assessed in fabricated chips by a set of methods that includes atomic force microscopy (AFM), Raman spectroscopy, and low-frequency noise. It is shown that local areas of residues on the graphene surface, which arisen due to the interaction of graphene with a photoresist at the initial stage of chips development, leads to a spread of chips resistance (R) within 1-10 kΩ and to an increase in the root mean square (RMS) roughness up to 10 times that can significantly impair reproducibility of graphene parameters in biosensors chips. It was observed that the control of the photoresist residues after photolithography (PLG) by AFM and subsequent additional cleaning allow reducing the spread of R values in chips to 1–1.6 kΩ and obtaining RMS roughness similar to the roughness in pristine graphene before PLG. Monitoring of the spectral density of low-frequency voltage fluctuation (SU), which provides integral information about the defect system and quality of the material, makes it possible to identify chips with low graphene quality and with inhomogeneously distributed compressive stresses areas by the type of frequency dependence SU (f).

Often, engineers with machining experience often judge machining state and tool life according to chips’ features. Engineers' experience is digitized in this study. During the cutting process, the cutting tool coming in contact with the workpiece produces a shear zone, which causes plastic deformation and shear slip. The chips closest to the shear zone can directly show the state of the tool and workpiece when the material is SKD61. This study used chip color, vibration, and current signal integration for prediction of machining state and cutting tool life. When the cutting tool wears increased, the chip surface color changed in the following way: purpleè purple blueè blue ècyan, or even green and yellow. When the cutting tool was in the accelerating wear phase, the color change was particularly obvious. The Back-Propagation Levenberg–Marquardt (BP-LM) predictive methodology was used to compare the predictive ability of voltage, vibration signal, and chip color. The Mean Absolute Percentage Error (MAPE) for the voltage signal was 12.28%, for the vibration signal it was 11.38%, and for the chip color combined with multi-sensor characteristics it was 7.85%. The MAPE of the chip color was the smallest. Using the General Regression Neural Network (GRNN) methodology, the MAPE for the voltage signal was 10.74%, for the vibration signal 7.96%, and for the chip color combined with multi-sensor characteristics was 6.59%. The MAPE of the chip color was the smallest. Obviously, the chip color combined with multi-sensor signals provided better predictive results than the vibration signal or voltage signal alone. There is currently no research on the usefulness of monitoring chip color for tool life prediction.

In the mold machining process, the cutting tool is worn with machining time, thereby affecting the surface accuracy, leading to poor workpiece dimensions, even fracture. At present, many studies have used multiple sensors to detect the machining conditions of cutting tool and workpiece, including indirect measurement method and direct measurement method. The indirect measurement method, which has been studied widely, mainly uses sensors to capture signals for subsequent data analysis; the direct measurement method mainly analyzes the state of cutting shear zone. Due to the cut-in of cutting tool in the machining process, the workpiece is dislocated rapidly, generating considerable amount of heat, which is transferred to the chips, inducing color change on the surface of chips. Many engineers with machining experience often judge the machining state and tool life according to the chips. The engineers' experience is digitized in this study, and indirect measuring sensors are used to predict the tool life, so as to attain the objective for smart manufacturing, the average percentage error of MAPE using single vibration and voltage eigenvalues as input features is 10%, the voltage signal characteristic values and vibration signal characteristic values are combined. Finally, the chip surface chromaticity eigenvalue is combined with signal characteristic value. The average prediction error of BP-LM method is 7.85%, the average prediction error of GRNN method is 6.59%. Therefore, when the eigenvalue of chip surface chromaticity is added to the prediction result, it can enhance the accuracy of cutting tool wear value prediction more effectively than single sensor signal characteristic value.

Non-canonical NF-kB signalling plays important roles in development and function of the immune system but also is deregulated in a number of inflammatory diseases. Although, NF-kB and HIF crosstalk has been documented, this has only been described following canonical NF-kB stimulation, involving RelA/p50 and the HIF-1 dimer. Here we report that the non-canonical inducer TNFSF14/LIGHT leads to HIF induction and activation in cancer cells. We demonstrate that only HIF-2a is induced at the transcriptional level following non-canonical NF-kB activation, via a mechanism dependent on the p52 subunit. Furthermore, we demonstrate that p52 can bind to the HIF-2a gene in cells. These results indicate that non-canonical NF-kB can lead to HIF signalling implicating HIF-2a as one of the downstream effectors of this pathway in cells.

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

We present the case of a 28-year-old male with a history of alcohol dependency and smoking, who presented with chest pain, shortness of breath, and altered sensorium. He exhibited severe metabolic acidosis, low platelet count, and acute kidney injury. Alcoholic ketoacidosis (AKA) was suspected due to ketonuria, metabolic acidosis, and ketonemia, compounded by electrolyte abnormalities and radiographic findings of pneumonia.Prompt intervention included electrolyte correction, thiamine supplementation, broad-spectrum antibiotics, and diuretics. Thiamine played a pivotal role in the patient's recovery, with significant improvement in consciousness observed within a day. After six days, the patient was discharged in stable condition, showing normal renal and hepatic function during follow-up.This case emphasizes the need for early recognition and comprehensive management in AKA, highlighting thiamine's crucial role in treatment success.

Alcohol abuse can result in detrimental multisystem effects. Chronic alcohol abuse is known to be associated with pathophysiological changes in multiple organs often resulting in life threatening clinical outcomes e.g. breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, alcohol-induced cardiomyopathy and heart failure as well as central nervous system disorders. In this review article, we will discuss the multisystemic effects of alcohol abuse and explore in greater detail alcohol’s impact on two main systems that result in pathophysiological changes i.e. the cardiovascular and central nervous systems.

Efficient use of the operating room (OR) is crucial for any hospital. One of the major inefficiencies in the OR is surgical cases not starting or finishing on time as scheduled. When a case is delayed, it affects all subsequent cases in that OR. This study uses discrete choice analysis to determine the significant factors, including team familiarity, that influence OR case on-time start and finish. A case is considered on-time if the documented procedure start and finish times are no more than 10 minutes after the scheduled start and finish times. The analysis uses surgical case data from a large tertiary referral hospital and academic center in Greenville, South Carolina. The case data includes all surgical cases (15,091) performed during regular workdays in 2013. Two binary logit models are developed: one for case on-time start and one for case on-time finish. Results indicate that higher team familiarity between surgeon and anesthesiologist, surgeon and circulating nurse, surgeon and scrub nurse, and surgeon and CRNA improve the likelihood of an OR case on-time start and on-time finish. This finding indicates that the OR scheduling staff in the study hospital make a concerted effort to schedule the surgical teams with members who have worked well together in the past.

In recent years, solid state terahertz (THz) modulators have obtained rapid progress with the widespread use of two-dimensional (2D) materials in the field of THz; however, challenges remain in preparing flexible THz modulators. In this study, flexible ferromagnetic nematic materials were prepared by doping thermotropic nematic liquid crystals 5CB into magnetic fluids, and the influence of hydrogen bonding in water was reduced by a self-made cyclic olefin copolymer (COC) microfluidic chip. THz modulation characteristics of magnetic fluid and ferromagnetic nematic liquid crystal (FNLC) under the induction of external magnetic field were compared using a THz time domain spectroscopy system. Under the action of a 91 mT magnetic field, the magnetic fluid has a maximum modulation depth (MD) of 54%. Under the same magnetic field, the maximum MD of the ferromagnetic nematic liquid crystal materials increase to 78% because of the rearrangement of Fe3O4 nanoparticles induced by the topological defect of the liquid crystal. We demonstrate that the magneto-optical effect is significantly enhanced in the ferromagnetic nematic liquid crystal hybrid system. This strategy of doping thermotropic nematic liquid crystals to enhance the magneto-optical effect has great potential for THz filtering, modulation, and sensing applications.

(1) Background: The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and disease activity and organ mani-festations in SLE patients. (2) Methods: We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4, and interleukin-6 (IL-6) levels, and antinu-clear and antiphospholipid antibody profiles. (3) Results: The median serum levels of sTfR (p>0.000001) and IL-4 (p<0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p<0.0001), a lower iron concentration (p=0.008), a lower value of total iron-binding capacity (TIBC) (p=0.03), and lower counts of RBC (p=0.004), HCT (p=0.0004), PLT (p=0.04), neutrophil (p=0.04), and lymphocyte (p<0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p=0.0005), HGB (p=0.0001) and HCT (p=0.008), and positively correlated with IL-4 (p=0.01). Elevated serum sTfR >2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71–464.78; p=0.001), ischemic heart disease (OR: 3.25 95 CI 1.02–10.40; p=0.04), lung manifestations (OR: 4.48 95 CI 1.44–13.94; p=0.01), and hematological manifestations (OR: 2.07 95 CI 1.13–3.79; p=0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22–0.80; p=0.008). Serum IL-4 was negatively correlated with CRP (p=0.003), and elevated serum IL-4 levels > 0.17 mg/l were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26–0.90; p=0.02). (4) Conclusions: In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, like diabetic foot ulcers, have increased significantly in the last years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: Methicillin-Resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had not proteolytic effects. MRSA infections increased cytokines expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to determine the therapeutic potential of these compounds by testing them in A375 cell-line derived xenograft in nu/nu mice. Animals were randomized into four groups (n=12/group) to receive subcutaneous administration of vehicle, 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 three times per week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results suggest a therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

(1) Background: In the United Kingdom, Ireland, Iceland, France, Spain, Portugal, and Italy a subject participating in a (bio) medical experiment is termed a guinea pig. In Germany (Versuchskaninchen), The Netherlands, all of Scandinavia, and most of Eastern Europe, the term rabbit is used for such a subject. We have searched for potential differences in attitudes towards biomedical research by inhabitants of the respective European countries by making an analysis of frequency and motivation to participate in biomedical experiments on both sides of the European rabbit borderline. (2) Methods: We have performed an analysis of the use of experimental animals for research in European countries as well as country specific scientific output in PubMed indexed literature. Attitudes towards biomedical research in European countries was derived from EU questionnaires. (3) Results: In biomedical experiments with animals, more guinea pigs are used in laboratories in “rabbit countries” than in “guinea pig countries”. Inhabitants of “rabbit countries” have a higher participation rate in biomedical experiments and donation of blood than people from “guinea pig” countries. The reasons to participate in a medical experiment are not purely altruistic, especially in “rabbit countries”. (4) Conclusions: inhabitants of European countries in which a person who participates in a biomedical experiment is labeled as an (experimental) rabbit participate more in biomedical experiments as well as tissue and organ donation. Motives to do so are not just altruistic, because financial reasons also play a role.

Organ transplantation centers set criteria for candidate qualification, which has led to disparate healthcare resource allocation practices affecting those with a substance use history. These individuals are denied organ transplants by committees and healthcare providers who assign them lower priority status. The lower priority argument claims that healthcare resources should not be provided equally to individuals failing to share responsibility for not doing enough in addressing the diseases associated with substance use. The purpose of this work is to explore the interrelatedness between the ethics of a merit-based system of moral responsibility and lower priority setting involved in healthcare resource allocation pertaining to those with substance use histories. An integral approach to the argument against the lower prioritists with a focus on the relationship between different organ allocation practices affecting substance users and the justification for resource allocation practices in healthcare and transplant committees. Lower priority setting is challenged, and an argument offered in which substance users are assigned higher priority when relying on “doing enough” in a merit-based system of moral responsibility. It is determined that one cannot substantiate assigning a lower priority status since a lack of success in rehab does not imply a lack of effort. Additionally, neither to confirmatory behavior, nor to non-conforming behavior may freedom be justifiably ascribed in a merit-based system of responsibility because freedom to choose can neither be established a priori, nor a posteriori with respect to meritorious behavior.

Electric torque wrenches play a crucial role in the assembly of high-strength bolts. This study focuses on three assembly processes for high-strength bolts and introduces a statistical analysis method to assess the quality of the bolt assembly. To enhance the performance, a novel, fully digital, Internet of Things (IoT) electric torque wrench is designed, incorporating a smart meter chip. This wrench achieves integration between the current sensor control method and the torque sensor control method using a simplified hardware circuit, ensuring high precision and stability. Additionally, this study employs the AC voltage self-stabilization method and Savitzky–Golay filtering method to enhance the accuracy and robustness of the wrench. Simulation experiments using Simulink and Matlab validate the effectiveness of these two methods. Furthermore, a cloud platform is utilized to enable rapid IoT access for the wrench, facilitating seamless connectivity and data transmission.