Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

In this work α-synuclein amyloid fibrils, formation of which is a biomarker of the Parkinson’s disease, were investigated with the use of fluorescent probe thioflavin T (ThT). Experimental conditions of the protein fibrillogenesis were chosen so that a sufficient number of continuous measurements can be performed to characterize and analyze all stages of this process. The reproducibility of fibrillogenesis and the structure of the obtained aggregates (that is a critical point for their further investigation) were proved using a wide range of physical-chemical methods. For determination of ThT—α-synuclein amyloid fibrils binding parameters sample and reference solutions were prepared with the use of equilibrium microdialysis. By absorption spectroscopy of these solutions ThT—fibrils binding mode with the binding constant about 10⁴ M⁻¹ and stoichiometry of ThT per protein molecule about 1:8 was observed. Fluorescence spectroscopy of the same solutions with the subsequent correction of the recorded fluorescence intensity on the primary inner filter effect allowed to determine another mode of ThT binding to fibrils with the binding constant about 10⁶ M⁻¹ and stoichiometry about 1:2500. Analysis of photophysical characteristics of the dye molecules bound to the sites of different binding modes allowed to assume the possible localization of these sites. Obtained differences in the ThT binding parameters to amyloid fibrils formed from α-synuclein and other amyloidogenic proteins, as well as in the photophysical characteristics of the bound dye, confirmed the hypothesis of amyloid fibrils polymorphism.

Since Hydrogen Sulfide (H2S) was recognized as a gas transmitter, its detection and quantifica-tion have become a hot research topic among chemists and biologists. In this area. fluorescent probes have shown great advantages: fast and strong responds, low detection limit and easy ma-nipulation. Here we developed a new fluorescent probe that detected H2S selectively among various bioactive and inorganic salts. This probe was based on the core structure of fluorescein and reacted with H2S through azide-reduction. Great linearity was achieved correlating fluores-cence intensity and H2S concentrations in solution. The detection of H2S in cancer cells was also achieved.

Lysine plays a crucial role in promoting development, enhancing immune function, and improving the function of central nervous system tissues. The two configurational isomers of amino acids have significantly different effects. Currently, methods for chiral recognition of lysine all have drawbacks such as expensive equipment and complicated detection processes, whereas fluorescence analysis boasts high sensitivity, strong selectivity, and simple operation. In this study, we synthesized four novel Binaphthyl-Amine (BINAM)-based fluorescent probes capable of specifically identifying the L-configuration of lysine among the twenty amino acids constituting human proteins. The enantiomeric fluorescence enhancement ratio (ef or ΔIL/ΔID) reached up to 15.29, demonstrating high enantioselectivity. We also evaluated the probe's recognition ability under different pH, reaction times, and metal ion conditions, as well as the Limit of Detection of the probe. Our findings indicate that this probe is a highly stable tool for detecting chiral lysine.

Fluorescent carbon dots (C-dots) were synthesized by one pot hydrothermal treatment of garlic juice at 180 °C for 7h. The as-prepared C-dots with an average diameter of 2.13±0.71 nm can be well dispersed, and show absinthe fluorescence with a quantum yield of 8.9% in water. The C-dots were fully characterized by TEM, XPS, XRD, and FTIR, respectively. Additionally, the as-prepared C-dots reveal nearly nontoxic to SW480 cells and can be used for cell imaging. The water solution of C-dots show sensitivity to pH values and metal ions, and also have a high selectivity to the Hg²⁺ ion among other transition metal ions, and achieve a high sensitive detection with the detection limit of 0.45 μM. The fluorescent C-dots are expected to be useful for the evaluation of mercury ions in environmental water system.

Mitochondrial hypochlorite (ClO-) plays important and often contradictory roles in maintaining the redox balance of mitochondria. Abnormal ClO- levels can induce mitochondrial inactivation and further cause cell apoptosis. Herein. we have developed an anthracene carboxyimide-based fluorescent probe mito-ACS for imaging mitochondrial ClO- in living cells. This probe exhibits some distinctive features as excellent resistance to photobleaching, high selectivity and sensitivity, as well as good water solubility. Mito-ACS showed a noticeable fluorescence response toward ClO-with a fast response (within 6 s) and a low detection limit (23 nM). Moreover, the introduction of triphenylphosphonium makes the probe soluble in water and selectively localizes to mitochondria. Furthermore, mito-ACS was successfully applied to image mitochondria ClO- in living cells with low toxicity. Remarkably. the less used fluorophore anthracene carboxyimide exhibiting excellent photostability and desirable optical properties provides a promising application prospect in biological systems.

A novel fluorescent probe (C460@Tb-MOFs) was designed and synthesized through encapsulating the fluorescent dye 7-diethylamino-4-methyl coumarin into terbium-based metal-organic framework by a simple ultrasonic impregnation method. It is impressive that this dye-modified metal-organic framework can specifically detect styrene and temperature upon luminescence quenching. The sensing platform of this material exhibit great selectivity, fast response and good cyclability toward styrene detection. It is worth mentioning that the sensing process undergoes a distinct color change from blue to colourless, providing conditions for accurate visual detection of styrene liquid and gas. The significant fluorescence quenching mechanism of styrene toward C460@Tb-MOFs is explored in detail. Moreover, the dye-modified metal-organic framework can also achieve temperature sensing from 298 to 498 K with high relative sensitivity at 498 K. The preparation of functionalized MOFs composites by fluorescent dyes provides an effective strategy for the construction of sensors for multifunctional applications.

Abundant of preparatory works have recognized that fluorescent sensors based on 8-aminoquinoline are popular tools to detect Zn2+ ions in environmental and biological applications. Along with these studies, researchers started to introduce a variety of carboxamido group into an 8-aminoquinoline molecule in forming 8-amidoquinoline derivatives. Therefore, this systematic review aims to introduce a general overview of the fluorophore 8-aminoquinoline as Zn2+ receptors and to provide comparisons of collected studies that related to 8-amidoquinoline derivatives as fluorophore probe of the sensor. According to PRISMA systematic searches strategy, 13 articles were analyzed for trends, research designs, results and discussion, subject samples, and remarks or conclusions. We found cross-sectional studies with four aspects in zinc sensing that have been targeted; binding studies via titration, detection's limit, interferences studies, and validation of the study. Hence, this paper also included assessments of those criteria and the trends of development of 8-amidoquinoline derivatives based-zinc fluorescent chemosensor. It also showed that most of the researches conducted in China. In conclusion, this study identified various research designs of fluorescent chemosensors based on 8-amidoquinoline prolong with the effectiveness and potential as a recognition probe to assist the detection of zinc. Hence, elucidation of those derivatives essential to be explored because more studies are needed to improve the sensing criteria of the zinc sensor

A fluorescent probe, N'-((3-methyl-5-oxo-1-phenyl-4, 5-dihydro-1H-pyrazol-4-yl) methylene)-2-oxo-2H-chromene-3-carbohydrazide (MPMC), was synthesized and characterized. Characterizations of the synthetic MPMC were conducted by proton nuclear magnetic resonance (1HNMR) spectroscopy and carbon-13 nuclear magnetic resonance spectroscopy (13C NMR). The fluorescence emission behaviors of probe MPMC towards diverse metal ions were detected and the probe exhibited high sensitivity and selectivity towards Cu2+ over other metal ions via quenching of its fluorescence. Furthermore, the existence of other metal actions made no difference on the fluorescence intensity of the MPMC-Cu2+ system apparently, that is, MPMC displayed a good anti-interference ability. Job’s plot of MPMC and copper ions indicated the detection limit was 15.16 nM (R2=0.9612) for the assayed actions, with a stoichiometric ratio of 1:1 for MPMC and Cu2+. Additionally, the color of MPMC probe solution changed from nearly colorless to yellow in the presence of Cu2+ in visible light, which the color change could be observed by the naked eye. Similarly, the color resolved bright yellow into blue in ultraviolet light. Also reusability studies indicated that MPMC probe was reusable. The pH effect of probe MPMC to Cu2+ had a broad range of pH detection 4.0 to 11.0. The response time of MPMC probe for determining Cu2+ was within 1 min. The recognition of Cu2+ by MPMC performed on pre-treated paper under sunlight and UV light both had a distinct colour change. Thus, the solid-state method for detecting Cu2+ with the naked-eye, was both economical and convenient.

Ultrafast pump-probe spectroscopic studies allow for deep insights into the mechanisms and timescales of photophysical and photochemical processes. Extracting valuable information from these studies, such as reactive intermediates' lifetimes and coherent oscillation frequencies, is an example of the inverse problems of chemical kinetics. This article describes a consistent approach for solving this inverse problem that avoids the common obstacles of simple least-squares fitting that can lead to unreliable results. The presented approach is based on the regularized Markov Chain Monte Carlo sampling for the strongly nonlinear parameters, allowing for a straightforward solution of the ill-posed nonlinear inverse problem. The software to implement the described fitting routine is introduced and the numerical examples of its application are given. We will also touch on critical experimental parameters, such as the temporal overlap of pulses and cross-correlation time and their connection to the minimal reachable time resolution.

Photoacoustic technology is a promising tool to provide morphological and functional information in biomedical research. To enhance the imaging efficiency, the reported photoacoustic probes have been designed coaxially involving complicated optical/acoustic prisms to bypass the opaque piezoelectric layer of ultrasound transducers, but leading to bulky probes and hindering the applications in limited space. Though the emergence of transparent piezoelectric materials helps to save the effort on the coaxial design, the reported transparent ultrasound transducers were still bulky. In this work, a miniature photoacoustic probe with an outer diameter of 4 mm was developed, in which an acoustic stack was made of the combination of transparent piezoelectric material and gradient-index lens as a backing layer. The transparent ultrasound transducer exhibited a high center frequency of ~47 MHz and a -6 dB bandwidth of 29.4%, which could be easily assembled with a pigtailed ferrule of a single-mode fiber. The multi-functional capability of the probe was successfully validated through the experiments of fluid flow sensing and photoacoustic imaging.

Fluorophore molecules can be monitored by fluorescence spectroscopy and microscopy which are highly useful and widely used techniques in cell biology, biochemistry and medicine (e.g., biomarker analysis, immunoassays, cancer diagnosis). Several fluorescent micro- and nanoparticle systems based on block copolymer micelles and cross-linked polymer networks, quantum dots, -conjugated polymers, and dendrimers have been evaluated as optical imaging systems. In this review, we highlight recent advances in the construction of fluorescent single-chain nanoparticles (SCNPs) which are valuable artificial soft nano-objects with tunable, small size (as small as 3 nm). In particular, the main methods currently available to endow SCNPs with fluorescent properties are discussed in detail, showing illustrative examples.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Color centers in diamond and nanodiamonds can be utilized as quantum sensors for measuring various physical parameters, particularly magnetic and electric fields, as well as temperature. Due to its small size and possible surface functionalization, fluorescent nanodiamonds are attractive systems for biological and medical applications since they can be used for intracellular experiments. This review focuses on fluorescent nanodiamonds for thermometry with nanoscale spatial resolution for living systems. The current state of the art, possible further development, and potential limitations will be discussed here.

Fluorescent hydrogels are promising candidate materials for portable biosensors to be used in point-of-care diagnosis because (1) they have a greater capacity for binding organic molecules than immunochromatographic test systems, determined by the immobilization of affinity labels within the three-dimensional hydrogel structure; (2) fluorescent detection is more sensitive than the colorimetric detection of gold nanoparticles or stained latex microparticles; (3) the properties of the gel matrix can be finely tuned for better compatibility and detection of different analytes; and (4) hydrogel biosensors can be made reusable and suitable for studying dynamic processes in real time. Water-soluble fluorescent nanocrystals are widely used for in vitro and in vivo biological imaging due to their unique optical properties, and hydrogels based on them allow preserving these properties in bulk composite macrostructures. Here we review the techniques for obtaining analyte-sensitive fluorescent hydrogels based on nanocrystals, the main methods used for detecting the fluorescent signal changes, and the approaches to the formation of inorganic fluorescent hydrogels via sol–gel phase transition using surface ligands of the nanocrystals.

Cell junction that is usually associated with dynamic cytoskeletons is essential for a wide range of cellular activities such as cell migration, cell communication, barrier function and signal transduction. Real-time observation of cell junction facilitates understanding of the mechanisms by which cell junction regulate relevant cellular activities. In this study, we examined the binding capacity of a modified tridecapeptide from Cx43 to cell junction protein ZO-1 and sought to create a fluorescent peptide that could be used to label cell junction. To introduce the fluorescent peptide into the cells, a cell-penetrating peptide was linked to the modified tridecapeptide and synthesized. The binding of the modified tridecapeptide was tested using pull down and immunoprecipitation assay. The ability of the peptide to label cell junction was assessed by adding it to fixed or cultured Caco-2 cells. Testing assay revealed that the Cx43-derived peptide can bind to ZO-1. Besides, the peptide was able to label cell junction of fixed cell, although no obvious cell junction labeling was observed clearly in living cells, probably due to the inadequate affinity. These results indicate that a peptide-based strategy for labeling cell junction may be feasible, and efforts to improve its affinity are warranted in the future.

Objectives: To compare the volumes and shapes of the coagulation zone (CZ) of a multi-probe RFA system (three RFA electrodes) and a single-probe MWA system from the same vendor in an ex-vivo bovine liver model. Material & Methods: A total of 48 CZs were obtained in bovine liver specimens with three different ablation system configurations (single-probe MWA vs. multi-probe RFA with 20 mm inter-probe distance [confluent CZ] vs. multi-probe RFA with 50 mm inter-probe distance [three individual CZ]) at 4-, 6-, 8-, and 10-min ablation time using a fixed ablation protocol. Ablation diameters were measured and ellipticity indices (EI) and volumes calculated. Calculations for all systems/configurations were compared. Results: Volumes and diameters increased with ablation time for all configurations. At 4- and 6-min ablation time volumes obtained with the RFA 50 mm setup, and at 8 and 10 min with the RFA 20 mm setup were the largest with 26.5 ± 4.1 mL, 38.1 ± 5.8 mL, 46.3 ± 4.9 mL, 48.4 ± 7.3 mL, respectively. The single-probe MWA could not reach the volumes of the RFA setups for any of the ablation times evaluated. EI were very similar and almost round for RFA 20 mm and single-probe MWA and differed significantly to the more ovoid ones for the RFA 50 mm configuration. Conclusion: The multi-probe RFA system employing three electrodes achieved significantly larger ablation volumes in both configurations (confluent CZ and three individual CZ) per time as compared to a single-probe MWA system in this ex-vivo bovine liver model.

Neural electrode insertion trauma impedes the recording and stimulation capabilities of numerous diagnostic and treatment avenues. Implantation leads to the activation of inflammatory markers and cell types, which is detrimental to neural tissue health and recording capabilities. Oxidative stress and inflammation at the implant site have been shown to decrease with chronic administration of antioxidant melatonin at week 16, but its effects on the acute landscape have not been studied. To assess the effect of melatonin administration in the acute phase, specifically the first week post-implantation, we utilized histological and q-PCR methods to quantify cellular and molecular indicators of inflammation and oxidative stress as well as two-photon microscopy to track the microglial responses in real-time. Histological results indicate that melatonin effectively maintained neuron density surrounding the electrode, inhibited accumulation and activation of microglia, astrocytes, and reduced oxidative tissue damage. The expression of the pro-inflammatory cytokines, TNF-α and IL-6, were significantly reduced in melatonin-treated animals. Additionally, microglia encapsulation of the implant surface was inhibited by melatonin as compared to control animals following implantation. Our results combined with previous research suggest that melatonin is a particularly suitable drug for modulating inflammatory activity around neural electrode implants both acutely and chronically, translating to more stable and reliable interfaces.

Photoacoustic imaging is attracting a great deal of interest owing to its distinct advantages over other imaging techniques such as fluorescence or magnetic resonance image. Availability of photoacoustic probes for reactive oxygen and nitrogen species (ROS/RNS) could shed light on a plethora of biological processes mediated by these key intermediates. Tetramethylbenzidine (TMB) is a non-toxic and non-mutagenic colorless dye that develops a distinctive blue color upon oxidation. In this work we have investigated the potential of TMB as photoacoustic probe for ROS/RNS. Our results indicate that TMB reacts with hypochlorite, hydrogen peroxide, singlet oxygen and nitrogen dioxide to produce the blue oxidation product, while ROS such as the superoxide radical anion, sodium peroxide, hydroxyl radical or peroxynitrite yield a colorless oxidation product. TMB does not penetrate Escherichia coli cytoplasm but is capable of detecting singlet oxygen generated in its outer membrane.

The luminescent properties of photocured aliphatic and aromatic network polycarbonate methacrylates containing organic fluorescent dyad have been studied. The dyad molecule includes two photosensitive fragments – tetraarylimidazole with a hydroxy group and azomethinocoumarin, in each of which excited state intramolecular proton transfer occurs, which leads to the appearance of two emissions - blue and green. It was established that the ratio of the intensities of these emissions depends on the excitation wavelength, as well as on the length, flexibility and polarity of the matrix oligomeric bridges.

Optical tissue imaging has several advantages over the routine clinical imaging methods, including non-invasiveness (does not change the structure of tissues), remote operation (avoids infection) and ability to quantify the tissue condition by means of specific image parameters. Dermatologists and other skin experts need compact (preferably pocket-size), self-sustained and easy-to-use imaging devices. The operational principles and designs of ten portable in-vivo skin imaging prototypes developed at the Biophotonics Laboratory of Institute of Atomic Physics and Spectroscopy, University of Latvia during the recent five years are presented in this paper. Four groups of imaging devices are considered. Multi-spectral imagers offer possibilities for distant mapping of specific skin parameters, so facilitating better diagnostics of skin malformations. Autofluorescence intensity and photobleaching rate imagers show a promising potential for skin tumor identification and margin delineation. Photoplethysmography video-imagers ensure remote detection of cutaneous blood pulsations and can provide real-time information on cardiovascular parameters and anesthesia efficiency. Multimodal skin imagers perform several of the above-mentioned functions by taking a number of spectral and video images with the same image sensor. Design details of the developed prototypes and results of clinical tests illustrating their functionality are presented and discussed.

In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

Neural microprobes represent an important component of neural prosthetic systems where implanted microprobes record the electro-potentials generated by specific thoughts in the brain and convey the signals to algorithms trained to interpret these thoughts. Here, we present novel elongated multi-site neural probe that can reach depths greater than 10mm. We hypothesize that reaching such depth allows the recording of cognitive signals required to drive cognitive prosthetics. The impedance of the recording sites on the probes was on the order of 500 kΩ at 1 kHz, which is consistent with probes used for neurophysiological recordings. The probes were made porous using Xenon Difluoride (XeF₂) dry etching to improve the biocompatibility and their adherence to the surrounding neural tissue. Numerical studies were performed to determine the reliability of the porous probes. We implanted the elongated probe in rats and show that the elongated probes are capable of simultaneously recording both spikes and local field potentials (LFPs) from various recording sites.

Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.

Biomass-derived carbon dots (CDs) are gaining much interest in recent times as it is a sustainable option with abundant availability, low cost, and tunable luminescence. Herein, we report a simple green synthesis method to produce highly fluorescent CDs from Eucalyptus globulus leaves using the one-pot hydrothermal approach. The fabricated CDs exhibit strong blue fluorescence with an excitation and emission maxima of 340 nm and 442 nm respectively. The highest quantum yield (QY) obtained was 60.7%. Due to its promising optical properties and biocompatibility, CDs can be a potential candidate for biosensing applications. Moreover, we employed a life cycle assessment (LCA) cradle-to-gate approach to study the environmental impacts of the synthesis strategy used for the fabrication of CDs. The results point out that citric acid is a main hotspot in CDs synthesis, regarding environmental impacts in most categories. This justifies the introduction of biomass, which reduces the amount of citric acid, thus leading to a more sustainable synthesis strategy for fabricating CDs.

Issues presented by the application of monoclonal antibodies in diagnostic assays and as curative agents can make the use of such molecules cost-prohibitive and sometimes even unsafe. This has warranted the development of short single-stranded oligonucleotides known as Aptamers. The structural malleability of these short DNA or RNA nucleotide segments allows them to exist in distinct conformations. SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a multi-step process for synthesis of aptamers. Each step of this procedure is governed by a diverse set of factors that influence production efficiency, binding affinity, and specificity of the oligonucleotides. Headway in aptamer research has been made in recent years by the introduction of newer iterations of the SELEX process. A greater number of studies are now being carried out to incorporate aptamers into existing disease detection tools and therapies. An overview has been given first on the key aptamer properties and the process of their production (with its newer iterations), contrasting each of them with that of monoclonal antibodies. Possible manifold applications afforded due to unique aptamer characteristics are also discussed. A keen review is further provided on the design, development and use of fluorescent aptamers in bioimaging, sequencing or profiling, and treatment of pathogenic bacteria and tumor cells.

In this work, we try to find a way to describe the physical law of micro-world under the frame of a space-time theory. By introducing the scalar fields $\mathcal{D}\left( x\right)$ and $\zeta\left( x\right) $, we rewrite the action of conventional field theory and the Lagrangian describing the motion of the particle, where a modified space-time relation is obtained. To test the correctness of this attempt, we demonstrate the Klein-Gordon equation by the Hamilton-Jacobi method in four dimensional form and present a time delay for the ground state of hydrogen atom.

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal-end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices remains a critical challenge, particularly in a way suitable for large scale adoption. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3 ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Directional dithering of a laser beam potentially limits the detection accuracy of a laser triangulation displacement probe. A theoretical analysis indicates that the measurement accuracy will linearly decrease as the laser dithering angle increases. To suppress laser dithering, a laser triangulation displacement probe with laser beam pointing control, which consists of a collimated red laser, a laser beam pointing control setup, a receiver lens, and a charge-coupled device, is proposed in this paper. The laser beam pointing control setup is inserted into the source laser beam and the measured object and can separate the source laser beam into two symmetrical laser beams. Hence, at the angle at which the source laser beam dithers, the positional averages of the two laser spots are equal and opposite. Moreover, a laser dithering compensation algorithm is used to maintain a stable average of the positions of the two spots on the imaging side. Experimental results indicate that with laser beam pointing control, the standard variance of the fitting error decreases from 0.3531 to 0.0100, the repeatability accuracy can be decreased from ±7mm to ±5 μm, and the nonlinear error can be reduced from ±6 %FS to ±0.16 %FS.

Esterases are hydrolases that catalyze the hydrolysis of esters into the corresponding acids and alcohols. The development of fluorescent probes for detecting esterases is of great importance due to their wide spectrum of biological and industrial applications. These probes can provide a rapid and sensitive method for detecting the presence and activity of esterases in various samples, including biological fluids, food products, and environmental samples. Fluorescent probes can also be used for monitoring the effects of drugs and environmental toxins on esterase activity, as well as to study the functions and mechanisms of these enzymes in several biological systems. Additionally, fluorescent probes can be designed to selectively target specific types of esterases, such as those found in pathogenic bacteria or cancer cells. In this review, we summarize the recent fluorescent probes described for the visualization of cell viability and some applications for in vivo imaging. On the other hand, Positron Emission Tomography (PET) is a nuclear-based molecular imaging modality of great value to study the activity of enzymes in vivo. We provide some examples of PET probes for imaging acetylcholinesterases and butyrylcholinesterases in brain, which are valuable tools for diagnosing dementia and monitoring the effects of anticholinergic drugs on the central nervous system.

The effect of the communication channel size on the transport and subsequent detection of chemical messengers is investigated on millimetric and micrometric channels. The transport of the information carriers, being characterized by an advective and a diffusive contribution, was simulated by varying the flow velocity and the diffusion coefficient. Then, to evaluate the information quality, the Intersymbol Interference (ISI) between two consecutive signals at a specific release delay was estimated. This allowed us to verify that operating under micrometric channel conditions has a larger flow velocity range to obtain completely separated successive signals and smaller release delays can be used between signals. The theoretical results were confirmed by developing a prototype molecular communication platform operating under microfluidic conditions, which enables communication through fluorescent nanoparticles, namely Carbon Quantum Dots (CQDs).

A micro Sagnac interferometer integration is proposed for electron cloud distributed sensors. The Sagnac interferometer consists of four microring probes integrated into a Sagnac loop. Each of the microring probes is embedded with the silver bars to form the plasmonic wave oscillation. At the center microrings, electrons are trapped and oscillated by the whispering gallery modes (WGMs), where the plasmonic antennas are established and applied for wireless fidelity (WiFi) and light fidelity (LiFi) transmissions for distributed sensors. The antenna gains are 2.59dB, 0.93dB, 1.75dB, and 1.16dB respectively for the four antennas formed at the center microrings. The polarized light of 1.50µm wavelength is fed into the interferometer input, which is polarized randomly into upstream and downstream directions. The polarization components can be obtained by the space-time modulation control. By controlling the electron cloud spin orientation, the space-time projection can be applied, and the ultra-high measurement resolution can be obtained in terms of fast switching time (change in phase). In manipulation, the applied stimuli are substituted by the change in input source power. The light input power variation causes a change in electron cloud density. Similarly, when the electron cloud is excited by the microscopic medium, which can be employed as the microscopic sensors. The WGM sensors have sensitivities of 1.35µm-2, 0.90µm-2, 0.97µm-2 and, 0.81µm-2, respectively. The WGMs behave as a four-point probe for the electron cloud distributed sensors, where the electron cloud sensitivities of 2.31 prads-1mm3 (electrons)-1, 2.27prads-1mm3 (electrons)-1, 2.22 prads-1mm3(electrons)-1, 2.38prads-1mm3(electrons)-1 are respectively obtained.

In the last two decades, extracellular vesicles (EVs) from the three domains of life, archae, bacteria and eukaryota, have gained increasing scientific attention. As such, the role of EVs in host-pathogen communication and immune modulation are being intensely investigated. Pivotal to EV research is the determination of how and where EVs are taken up by recipient cells and organs in vivo, which requires suitable tracking strategies including labelling. Labelling of EVs is often performed post-isolation which increases risks of non-specific labelling and the introduction of labelling artefacts. Here we exploited the inability of helminths to de novo synthesise fatty acids to enable labelling of EVs by whole organism uptake of fluorescent lipid analogues and the subsequent incorporation in EVs. We showed uptake of DOPE-Rhodamine in Anisakis spp. and Trichuris suis larvae. EVs isolated from supernatant of Anisakis spp. labelled with DOPE-Rhodamine were characterised to assess effects of labelling on size, structure and fluorescence of EVs. Fluorescent EVs were successfully taken up by the human macrophage cell line THP-1. This study therefore presents a novel staining method that can be utilized by the EV field in parasitology and potentially across multiple species.

Abstract: We have filled a 24 mm diameter glass sphere with a transparent polymer-gel that is radio-fluorogenic, i.e. it becomes (permanently) fluorescent when irradiated, with an intensity proportional to the local dose deposited. The gel consists of >99.9% tertiary-butyl acrylate (TBA) pre-polymerized to ~15% conversion, and ~100 ppm maleimido-pyrene (MPy). Its dimensions and physical properties are close to those of the vitreous body of the human eye. We have irradiated the gel with a 3 mm diameter, 200 kVp X-ray beam with a dose rate of ~1 Gy/min. A 3D (video) view of the beam within the gel has been constructed from tomographic images obtained by scanning the sample through a thin sheet of UV light. To minimize optical artifacts, the cell was immersed in a square tank containing a refractive-index-matching medium. The 20%-80% penumbra of the beam was determined to be ~0.4 mm. The research was a preparatory investigation of the possibility of using the method to monitor the millimetre diameter proton pencil beams used in ocular radiotherapy.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

This paper explores the Wilsonian renormalization group of probe-D-branes, focusing on the Dirac-Born-Infeld (DBI) action. The analysis involves deriving the constant of motion and formulating the Wilsonian renormalization group equation. The study extends to the infrared regime, considering both zero and non-zero temperatures. Additionally, thermodynamic aspects related to the functional form of the grand potential are discussed. The investigation provides insights into the renormalization of probe-D-branes and their thermodynamic properties.

Porous metals possess low bulk density, large specific strength, high stiffness and special thermal, electromagnetic and acoustic conductivity, so that porous metals are widely used in filtration and separation, flame retardant explosion-proof, biomedical application, etc. Compared with its corresponding dense metal, the presence of porous structures also leads to different corrosive performances of porous metal. So, some researches have utilized weight loss method, electrochemical impedance to evaluate porous metals’ corrosion behavior; however, the influence of pore structure on metal corrosion is still controversial, and present methods used for analyses of porous metals’ corrosion are statistical averages of the corrosion behavior of the entire porous material, which cannot accurately reflect the corrosion behavior inside the pore structure. Herein, we prepare porous copper samples with 0, 24, 72, 96 pores using mechanical process, and employ scanning kelvin probe combined with electrochemical polarization curve and impedance spectroscopy to test the corrosion performance of the porous copper in static and dynamic NaCl solution. The relevant results indicate that in static solution, the corrosion resistance of samples gradually increases with the rise of the number of pores. By contrast, the sample with 24 pores exhibits more susceptible to corrosion than the sample without pore.

Electrophysiological mapping (EM) using acute electrode probes is a common procedure performed during functional neurosurgery. Due to their constructive specificities, the EM probes are lagging in innovative enhancements. This work addressed complementing a clinically employed EM probe with carbonic and circumferentially segmented macrocontacts that are operable both for neurophysiological sensing ("recording") of local field potentials (LFP), and for test stimulation. The paper illustrates in-depth the development, that is based on direct writing of functional materials. The unconventional fabrication processes were optimized on planar geometry and then transferred to the cylindrically thin probe body. We report and discuss on the constructive concept and architecture of the probe, characteristics of the electrochemical interface deduced from voltammetry and chronopotentiometry, and the results of in vitro and in vivo recording and pulse stimulation tests. Two and three directional macrocontacts were added on probes having shanks of 550 and 770 m diameters and 10-23 cm lengths. The graphitic material presents a ~2.7 V-wide, almost symmetric water electrolysis window, and an ultra-capacitive charge transfer. When tested with 150 s biphasic current pulses, the interfacial polarization stayed safely away from the water window for pulse amplitudes up to 9 mA (135 C/cm2). The in vivo experiments on adult rat models confirmed the high-quality sensing of LFPs. Additionally, the in vivo-prevailing increase of the electrode impedance and overpotential are discussed and modeled by an ionic mobility-reducing spongiform structure; this restricted diffusion model gives new applicative insight into the in vivo-uprisen stimulation overpotential.

We put forward a co-axial pump(optical)-probe(X-rays) experimental concept and show performance of the optical component. A Bessel beam generator with a central 100 micrometers-diameter hole (on the optical axis) was fabricated using femtosecond (fs) laser structuring inside a silica plate. This flat-axicon optical element produces a needle-like axial intensity distribution which can be used for the optical pump pulse. The fs-X-ray free electron laser (X-FEL) beam of sub-1 micrometer diameter can be introduced through the central hole along the optical axis onto a target as a probe. Different realisations of optical pump are discussed. Such optical elements facilitate alignment of ultra-short fs-pulses in space and time and can be used in light-matter interaction experiments at extreme energy densities on the surface and in the volume of targets. Full advantage of ultra-short 10 fs X-FEL probe pulses with fs-pump(optical) opens an unexplored temporal dimension of phase transitions and the fastest laser-induced rates of material heating and quenching. A wider field of applications of fs-laser-enabled structuring of materials and design of specific optical elements for astrophotonics is presented.

Formalin-Fixed Paraffin Embedded (FFPE) tissues are a valuable resource in studying different markers and mechanistic molecules (protein, DNA and RNA) in order to understand the etiology of different cancers as well as many other diseases. Degradation and modification of RNA is the major challenge in utilizing FFPE tissue samples in medical research. Recently, non-protein coding transcripts long non-coding RNAs (lncRNAs), have gained significant attention due to their important biological actions and potential involvement in cancer. There is no validated method except qRTPCR or RNAseq to evaluate and study lncRNA expression. We have standardized and are reporting a sensitive Z probe based in situ hybridization method to identify, localize and quantitate lncRNA in FFPE tissues. This assay is sensitive to single transcript and localizes lncRNA in individual cells within tumor. We have characterized a tumor suppressor lncRNA-NRON (non coding repressor of NFAT), which is scarcely expressed, a moderately expressed oncogeneic lncRNA UCA1 (urothelial cancer associated 1), and a highly studied and expressed lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript1) in different cancers. High MALAT1 staining was found in colorectal, breast and pancreatic cancer. MALAT1 expression increased with the progression of the stage in colorectal cancer and invasiveness in breast cancer.

In this paper, the effects on the rheological properties, particle size distribution, and fluorescence properties of red wine were investigated under microwave irradiation, and the mechanism of the effects of microwave irradiation on the sensory properties of red wine was discussed. The results showed that the effect of microwave on the rheological properties in red wine could be fitted by the Power-law model and Carson model, through the analysis of the rheological constants, yield stress, and viscosity coefficient of wine, it was found that microwave treatment could improve leg phenomenon and thickening effect by the change of rheological properties; the particle size distribution in wine indicated that microwave irradiation did change the particle size distribution through friction effect and oxidative polymerization, resulting in the wine’s visual effect and mouthfeel; the wine quality could be improved by enhancing the fluorescence intensity under different microwave conditions, which meant that microwave technology could speed up the formation of fluorescent substances, such as the polymerization of flavan-3-ols. In conclusion, microwave treatment could modify the sensory characteristics of wine, and further provide the theoretical basis for the application of microwave in winemaking.

As one of the most critical parameters to evaluate the quality and performance of mobile phones, real-time temperature monitoring of the mobile phone integrated chips is vitally important in the electronics industry. Although several different strategies for chip surface temperature measurement have been proposed in recent years, distributed temperature monitoring with the high spatial resolution is still a hot issue to be solved urgently. In this work, a fluorescent film material with photothermal properties containing thermosensitive upconversion nanoparticles (UCNPs) and polydimethylsiloxane (PDMS) is fabricated for chip surface temperature monitor-ing. The presented fluorescent films have thicknesses ranging from 23 to 90 μm and are both flexible and elastic. Using the fluorescence intensity ratio (FIR) technique, the temperature sens-ing properties of these fluorescent films are investigated. The maximum sensitivity of the fluo-rescent film was measured to be 1.43% K-1 at 299 K. By testing the temperature at different posi-tions of the optical film, a distributed temperature monitoring with a high spatial resolution down to 10 μm on the chip surface is successfully achieved. It is worth mentioning that the film maintains stable performance even under pull stretch up to 100%. The correctness of the method is verified by taking infrared images of the chip surface with an infrared camera. These results demonstrate that the as-prepared optical film is a promising anti-deformation material for high spatial resolution temperature monitoring on-chip surfaces.

Quantitative polymerase chain reaction (qPCR) is the gold standard approach for detecting a variety of pathogens either via probe-based or SYBR green detection chemistry. Generally, probe-based detection is more specific than SYBR green chemistry. This report describes work done in using a FAM probe targeting a specific segment of the human KRAS gene for detecting presence and relative abundance of the gene in human gastric CloTest samples. Results indicate ineffective detection of the human KRAS gene in samples that are shown to harbor the gene through a similar qPCR assay using SYBR green detection chemistry. Such observations point to inability of the designed FAM probe to bind to target segment of the human KRAS gene that suggests a region of rapid genomic evolution that require close surveillance in the public health community. Given its rapid genomic evolution, this probe region may be an important region in the human KRAS gene playing critical functional roles in either molecular recognition or other structural functions. Overall, human KRAS gene may be undergoing rapid genomic evolution, and qPCR probes targeting specific segment of the gene may be rendered ineffective in short time clinically, thereby, making SYBR green qPCR assay a more reliable choice.

A developed six-port reflectometry (SPR) system was integrated to measure the relative permittivity of tumor and normal breast tissue for medical diagnostic purpose. In order to obtain an accurate and precise measurement, the calibration process was done to the SPR using the well-known three-standard technique. Next, the studied dielectric probe was connected to the calibrated measurement-port of the SPR. The open end of the probe aperture was dibbed into the normal and tumor synthetic breast tissue samples to measure the synthetic breast tissues dielectric constant, ɛrʹ, and loss factor, ɛrʺ in the frequency range of 1.5 GHz to 3.3 GHz. Finally, the comparative studies were conducted between commercial VNA with Keysight 85070E dielectric probe and the studied SPR-probe system based on the measured magnitude of the reflection coefficient, phase shift, dielectric constant, and loss factor of the synthetic breast samples. The maximum absolute errors of the measured reflection coefficient magnitude, phase shift, dielectric constant, and loss factor were found to be 0.01, 1.07°, 1.12, and 0.75, respectively. It was ascertained that the predicted dielectric constant, ɛrʹ, is able to differentiate between normal, (ɛrʹ < 50) and tumor, (ɛrʹ > 50) breast tissues.

The characterization of thin-film solar cells is of huge importance for obtaining high open-circuit voltage and low recombination rates from the interfaces or within the bulk of the main materials. Among the many electrical characterization techniques, the two- and four-wire probe using the Cascade instrument is of interest since the resistance of the wires, and the electrical contacts can be excluded by the additional two wires in 4-wire probe configuration. In this paper, both two and four-point probes configuration are employed to characterize the CIGS chalcogenide thin-film solar cells. The two-wire probe has been used to measure the current-voltage characteristics of the cell which results in a huge internal resistance. Therefore, the four-wire connection is also used to eliminate the lead resistance to enhance the characterization’s accuracy. The load resistance in the two-wire probe diminishes the photogenerated current density at smaller voltage ranges. In contrast, the proposed four-wire probe collects more current at higher voltages due to enhanced carrier collection efficiency from contact electrodes. The current conduction mechanism is also identified at every voltage region represented by the value of the ideality factor of that voltage region. It is observed that a long time given to the charge collection results in increased current density at a higher voltage. According to the results and device characteristics, a novel double-diode model is suggested to extract the saturation current density, shunt and series resistances and the ideality factor of the cells. These cells are shown to be efficient in terms of low recombination at the interfaces and with lower series resistance as the quality of the materials is in its most possible conductive form. The measured internal resistance and saturation current density and ideality factor of the two measurement configuration is measured and compared.

Genetic engineering and directed evolution are effective methods to address the low yield and poor industrialization level of microbial target products. The current research focus is on how to efficiently and rapidly screen beneficial mutants from constructed large-scale mutation libraries. Traditional screening methods such as plate screening and well plate screening are severely limited in their development and application due to their low efficiency and high costs. In the past decade, microfluidic technology has become an important high-throughput screening technology due to its fast speed, low cost, high automation, and high screening throughput, and it has developed rapidly. Droplet-based microfluidic high-throughput screening has been widely used in various fields such as strain/enzyme activity screening, pathogen detection, single-cell analysis, drug discovery, and chemical synthesis, and has been widely applied in industries such as materials, food, chemicals, textiles, and biomedicine. In particular, in the field of enzyme research, droplet-based microfluidic high-throughput screening has shown excellent performance in discovering enzymes with new functions, improved catalytic efficiency or stability, acid-base tolerance, etc. Currently, droplet-based microfluidic high-throughput screening technology has achieved high-throughput screening of enzymes such as glycosidase, lipase, peroxidase, protease, amylase, oxidase, and transaminase, as well as high-throughput detection of products such as riboflavin, coumarin, 3-dehydroquinate, lactic acid, and ethanol. This article reviews the application of droplet-based microfluidics in high-throughput screening, with a focus on high-throughput screening strategies based on UV, visible, and fluorescence spectroscopy, including labeled optical signal detection screening, as well as label-free electrochemical detection, mass spectrometry, Raman spectroscopy, nuclear magnetic resonance, etc. Furthermore, the research progress and development trends of droplet-based microfluidic technology in enzyme modification and strain screening are also introduced.

Glutamate excitotoxicity is implicated in the pathogenesis of many disorders, including stroke, traumatic brain injury, and Alzheimer’s disease, for which central insulin resistance is a comorbid condition. Massive glutamate release primarily through ionotropic N-methyl-D-aspartate receptors (NMDARs) causes a sustained rise in [Ca2+]i, followed by mitochondrial depolarization and an increase in intracellular O2• (superoxide) production. Recently, we found that insulin protected neurons against excitotoxicity by diminishing the delayed calcium deregulation (DCD), However, a role of insulin in superoxide production in excitotoxicity still needs to be clarified. The present study is aimed to investigate the effects of insulin on glutamate-evoked superoxide generation and DCD using the fluorescent indicators dihydroethidium, MitoSOX Red, and Fura-FF in rats cultured cortical neurons. We found that insulin significantly diminished both the intracellular and mitochondrial superoxide production in neurons exposed to glutamate and there was a strong linear correlation between [Ca2+]i and intracellular superoxide. MK 801, an inhibitor of NMDAR-gated Ca2+ influx, completely abrogated the glutamate effects in both the presence and absence of insulin. In experiments on sister cultures, insulin diminishes neuronal death. Thus, collectively, data obtained suggest that insulin diminishes glutamate-induced superoxide production in neurons via fall of [Ca2+]i increased and thereby improves viability of neurons

Current paper reviews applications of luminescence bioassays for monitoring low-intensity factors, namely, radioactivity of different types (alpha, beta and gamma), and bioactive compounds (humic substances and fullerenols). Luminescence intensity is taken as a physiological parameter of luminous organisms. High rates of luminescence response can provide (1) a proper number of experiments under comparable conditions and, therefore, proper statistical processing, with this being highly important for ‘noisy’ low-dose exposures; (2) non-genetic, i.e. biochemical and physicochemical mechanisms of cellular response, in accordance to “exposome” concept. Bioassays based on luminous marine bacteria, their enzymes, and fluorescence coelenteramide-containing proteins were used to compare results of low-intensity exposures at cellular, biochemical and physicochemical levels, respectively. Results of the cellular exposures were discussed in terms of hormesis concept. Bioluminescence time dependence under low-dose radiation exposures corresponded to hormesis or threshold models; no bioluminescence monotonic dependency on intensity of exposure (dose rate, radioactivity, concentration) was found. Bioluminescence activation and absence of its dependency on intensity of exposure can be accepted as features of cellular adaptive response. Changes of biological luminescence were analyzed and discussed for bioassays of lower organization level – enzymes and florescent protein.

Far-red fluorescent reporter genes can be used for tracking cells non-invasively in vivo using fluorescence imaging. Here, we investigate the effectiveness of the far-red fluorescent protein, E2-Crimson (E2C), for tracking mouse embryonic cells (mESCs) in vivo following subcutaneous administration into mice. Using a knock-in strategy, we introduced E2C into the Rosa26 locus of an E14-Bra-GFP mESC line, and after confirming that the E2C had no obvious effect on the phenotype of the mESCs, we injected them into mice and imaged them over 9 days. The results showed that fluorescence intensity was weak, and cells could only be detected when injected at high densities. Furthermore, intensity peaked on day 4 and then started to decrease, despite the fact that tumour volume continued to increase beyond day 4. Histopathological analysis showed that although E2C fluorescence could barely be detected in vivo at day 9, analysis of frozen sections indicated that all mESCs within the tumours continued to express E2C. We hypothesise that the decrease in fluorescence intensity in vivo was probably due to the fact that the mESC tumours became more vascular with time, thus leading to increased absorbance of E2C fluorescence by haemoglobin. We conclude that the E2C reporter has limited use for tracking cells in vivo, at least when introduced as a single copy into the Rosa26 locus.

In this paper, a new probe-fed wideband antenna with a circular patch and a coupled stacked ring is proposed. This antenna can be implemented by using suspended microstrip technique with total thickness of about 0.09 of center frequency wavelength. By using a novel feeding technique, in this antenna about 40 % reduction in area compared to similar works can be achieved. The obtained bandwidth in this antenna according to simulation results satisfying VSWR<2 is about 27.5 % from 5 to 6.6 GHz using two resonant frequencies. Also a comprehensive theoretical and parametric study is done in order to facilitate its designing in various frequency bands.

Organic light-emitting diodes (OLEDs) have ushered in a technological revolution with their remarkable impact on diverse sectors of our daily lives. These versatile devices known for their outstanding display and lighting capabilities, have become indispensable components in various industries including smartphones, tablets, televisions, and automotive applications. This paper delves into the development of a group of twisted donor-acceptor-donor (D-A-D) derivatives incorporating bicarbazole and benzophenone structures for potential use as blue emitters in OLEDs. The synthesized compounds, namely DB14, DB23 and DB29, were designed with various alkyl side chains to enhance their film forming properties as for blue emitters. Characterization and evaluation of these derivatives included photophysical, electrochemical, thermal, and electroluminescent analysis. Some of the OLED devices incorporating these emitters demonstrated promising performance with maximum current efficiency (CEmax) of 2.6 cd/A and external quantum efficiency (EQEmax) of 5.3%. Notably, the DB23 emitter exhibited the highest EQE among all devices. The study also emphasizes the influence of host-guest energy transfer, optimal doping concentrations, and molecular structures on device performance. This research not only contributes to the understanding of advanced OLED materials but also provides insights into designing efficient blue emitters for future display and lighting applications, thereby advancing the field of organic electronics.

Glyphosate　(GLYP)　is a broad-spectrum, non-selective, organic phosphine post emergence herbicide registered for use on many food and non-food field. Herein, we developed a biosensor (Mbs@dsDNA) based on carboxylated modified magnetic beads incubated with NH2-polyA and then hybridized with polyT-glyphosate aptamer and complementary DNA. Afterward, a quantitative detection method based on qPCR was established.　When the glyphosate aptamer on Mbs@dsDNA specifically recognized glyphosate, a complementary DNA is released and then enters the qPCR signal amplification process. The linear range of the method was 0.1-5 μg/mL, and the detection limit was set at 0.1 μg/mL. The recoveries in tap water were ranged from 103.4 ~ 104.9%, and the relative standard deviations (RSDs) were < 1%. The aptamer proposed in this study has a good potential for recognizing glyphosate. The detection method combined with qPCR might have a good application prospect in detecting and supervising other pesticide residues.

Early identification of fetal abnormalities is a huge challenge for modern obstetrics. Quantitative fluorescent polymerase chain reaction (QF-PCR) has quickly become an effective means of chromosome anomaly detection due to its advantages in terms of timing, manpower and accuracy. The QF-PCR results also make a significant change in clinicians’ attitude to some extent, assisting them providing parents with professional and valuable advice on pregnancy management. In this review, the advantages and drawbacks of QF-PCR will be explored. By reviewing studies published in Vietnamese Medical Journals, we conclude QF-PCR can become a potential screening test in the field of prenatal diagnosis.

(1) Background: Myelodysplastic syndromes (MDS) are a group of diseases that affect the morphology and function of neutrophils. Rapid diagnosis of MDS is crucial for the initiation of treatment that can vastly improve disease outcome. (2) methods: In this work, we present a new approach for detecting morphological differences between neutrophils isolated from blood samples of high risk MDS patients and that for patients and blood bank donors (BBDs). First, using fluorescent flow cytometry CD66b positive cells were stained with 2′,7′-dichlorofluorescin diacetate (DCF) and Hoechst. Secondly, we imaged the cells using interferometric phase microscopy (IPM) without utilizing cell staining. (3) Results: flow cytometry results show MDS patients present different dispersion patterns compared to BBDs. BBDs present two distinct subpopulations (one of these are the H cells constituting 16% for neutrophils) whereas MDS patients present only 4% of this subpopulation. IPM results are consistent with this pattern: ~20% of BBDs neutrophils were characterized as H cells and whereas MDS patients present only ~4% of these cells. (5) Conclusion- IPM can be utilized for diagnosis of complex hematological pathologies such as MDS.

Chitosan and its derivatives as a biocompatible, biodegradable polymer that has been well-established in biotechnology and medicine as the nanogels and nanofilms forming material, has a number of practical applications in the field of the supply of medicines, food colloids, agrotechnology, as well. In this paper, the focus of attention is directed to the study of the physico-chemical principles of the formation of gels and nano-particles using fluorescence spectroscopy methods. We have obtained chitosan (Chit5) and pegylated chitosan (Chit5-PEG) particles with an average size of 170 or 400 nm, respectively by counterflow extrusion method. The paper presents three based fluorescent probes sensitive to the formation of chitosan particles: congo red, malachite green as well as covalently attached pyrene-label. Dyes fluoresce about an order of magnitude brighter in the composition of chitosan nanogel particles or in mscrogels. With these fluorescence probes, the pH- and temperature-dependent behavior of polymers was studied, and the influence of the genipin -based crosslinking agent on the gel formation parameters, such as kinetics and concentration dependence of the nanoparticles formation accompanied by sharply increases in the fluorescence intensity of dyes was evaluated. A sensitive approach for tracking gelation and including of small drug molecules and protein by FRET using a pyrene-tryptophan donor-acceptor pair is proposed using tryptophan or ovalbumin as fluorophores-donors. Upon nanogel formation FRET effect is observed manifested in sharp increase if the fluorescence intensity of the pyrene (acceptor). Thus, the application of the fluorescent probes with FRET function for monitoring the gelation and nanoparticles formation as well as drug encapsulation in chitosan-based parts, which have broad prospects in biomedical practice and food industry.

In this study, ozone oxidation experiment was carried out for the removal of fluorescent whitening agent which is widely used in textile dyeing and paper industry. The stilbene fluorescent whitening agent has been industrialized since the earliest, and the amount of current production is the highest. Due to the characteristics of the fluorescent whitening agent that cannot be removed by conventional wastewater treatment methods, the fluorescent whitening agent in wastewater treatment has difficulty in using as recycled water in the process. Pre-treatment ozone oxidation experiment was conducted prior to the introduction of Membrane Bio Reactor (MBR) treatment process by converting biodegradable materials into biodegradable materials. The removal efficiencies of fluorescent whitening agents, a diaminostilbene disulfonic acid derivative by ozone oxidation were evaluated by UV254 Scan, COD, T-N and color using a synthetic wastewater sample (COD=433.0 mg/ℓ) and paper and paper mill wastewater (COD=157.2 mg/ℓ).

We report the development of an extrinsic self-healing coating system that shows no fluorescence from the intact coating, yellowish fluorescence in cracked regions, and greenish fluorescence in healed regions, thus allowing the separate monitoring of cracking and healing of coatings. This fluorescence monitoring self-healing system consisted of a top coating, an epoxy matrix resin containing mixed dye-loaded in single microcapsule. The dye-loaded microcapsules consisted of a poly(urea-formaldehyde) shell encapsulating a healing agent containing MAT-PDMS and styrene, a photo-initiator and a mixture of two dyes, one that fluoresces only in the solid state (DCM) and a second that fluoresces dramatically increased in the solid than solution state (4-TPAE). A mixture of the healing agent, photo-initiator and the two dyes was yellow due to fluorescence from DCM. On UV curing of this mixture, however, the color changed from yellow to green and the fluorescence intensity increased due to fluorescence from 4-TPAE in the solid state. When a self-healing coating embedded with microcapsules containing the DCM/4-TPAE dye mixture was scratched, the damaged region exhibited a yellowish color that changed to green after healing. Thus, the self-healing system reported here allows the separate monitoring of cracking and healing based on changes in fluorescence color.

In this work, we firstly explored a mild, clean, and highly efficient approach for the synthesis of graphene quantum dots (GQDs). GQDs with carboxyl groups or amino groups, were prepared from one-pot environmentally friendly method assisted by hydrogen peroxide, respectively. It was proved that carboxyl groups played an important role in the fluorescence quenching. Based on these findings, we developed a novel fluorescent nanosensor by combining molecularly imprinted polymers (MIPs) with carboxyl functionalized GQDs for the determination of tetracycline (TC) in aqueous samples. The nanocomposite was prepared using a sol-gel process. GQDs-MIPs showed strong fluorescent emission at 410 nm when excited at 360 nm, which was subsequently quenched in the presence of TC. Under optimum conditions, the fluorescence intensity of GQDs-MIPs decreased in response to the increase of TC concentration with good linearity rage of 1.0-104 µg L-1. The limit of detection was determined to be 1 µg L-1. The fluorescence intensity of GQDs-MIPs was more strongly quenched by TC compared to the corresponding non-imprinted polymers, GQDs-NIPs. With the high sensitivity, the material was also successfully worked for the detection of TC in real spiked milk samples.

This study introduces a compact Raman spectrometer with a 1064 nm excitation laser coupled with a fiber probe and an inexpensive motorized stage, offering a promising alternative to widely used Raman imaging instruments with 785 nm excitation lasers. The benefits of 1064 nm excitation for biomedical applications include further suppression of fluorescence background and deeper tissue penetration. The performance of the 1064 nm instrument in detecting cancer in human bladder resectates is demonstrated. Raman images with 1064 nm excitation were collected ex vivo from 10 human tumor and non-tumor bladder specimens and the results are compared to previously published Raman images with 785 nm excitation. K-Means cluster (KMC) analysis is used after pre-processing to identify Raman signatures of control, tumor, necrosis, and lipid-rich tissues. Hierarchical cluster analysis (HCA) groups the KMC centroids of all specimens as input. The tools for data processing and hyperspectral analysis were compiled in an open source Python library called SpectraMap (SpMap). In conclusion, the 1064 nm Raman system can differentiate between tumor and non-tumor bladder tissues in a similar way to 785 nm Raman spectroscopy. These findings hold promise for future clinical hyperspectral imaging.

A surgical microscope is large in size, which makes it impossible to be portable. The distance between the surgical microscope and the observation tissue is 15–30 cm, and the adjustment range of the right and left of the camera is a maximum of 30°. Therefore, the surgical microscope is generated attenuation (above 58%) of irradiation optical source owing to the long working distance. Moreover, the observation of tissue is affected because of dazzling by ambient light as the optical source power is strong (55 to 160 mW/cm2). Further, observation blind spot phenomena will occur due to the limitations in adjusting the right and left of the camera. Therefore, it is difficult to clearly observe the tumor. In this study, a compact pen-type probe with a portable surgical microscope is presented. The proposed surgical microscope comprises a small and portable pen-type probe that can adjust the working distance between the probe and the observed tissue. In addition, it allows the adjustment of the viewing angle and fluorescence brightness. The proposed probe has no blind spots or optical density loss.

This work aimed to characterize a DBD plasma equipment through optical and electrical measurements, seeking to obtain a greater knowledge of the plasma production process and how it behaves through the adopted parameters, such as frequency and voltage applied between electrodes, at a fixed distance of 1.7 mm. In order to measure them, three different characterization techniques were applied. The first method was the Lissajous figures, a technique quite effective for a complete electrical characterization of DBD equipment. The second technique used was the Optical Emission Spectroscopy, a tool used for the diagnosis of plasma, being it possible to identify the excited species produced in filamentary and diffuse discharge in the plasma. And finally, the triple Langmuir probe technique was used to obtain the electron temperature and electron density. Based on this study, it was possible to identify the equipment efficiency in different regimes. The electron temperature measurement for both systems analyzed were 27.96 eV and 20.69 eV to the filamentary and diffuse regimes, respectively. The density of electrons number to these regimes were 1.09 × 10²¹ m⁻³ and 1.56 × 10²¹ m⁻³.

This paper focuses on the non-destructive dielectric measurement for low-loss planar materials with a thickness of less than 3 mm using a large coaxial probe with an outer diameter of 48 mm. The aperture probe calibration procedure required only to make a measurement of the half-space air and three offset shorts. The reflection coefficient for the thin material is measured using a Keysight E5071C network analyzer from 0.3 MHz to 650 MHz and then converted to a relative dielectric constant and tangent loss via closed form capacitance model and lift-off calibration process. Measurement error of dielectric constant, Δε_r is less than 2.5 % from 1 MHz to 400 MHz and the resolution of loss tangent, tan δ measurement is capable of achieving 3×10^-3.

In this study, a simple, easy and convenient fluorescent sensing system for detection of vascular endothelial growth factor (VEGF) based on VEGF aptamers, aptamer-complementary fluorescence-labeled probe and streptavidin magnetic beads was developed in only one single tube. The VEGF is the most important biomarker in cancer angiogenesis, and is investigated that serum VEGF level was various according to the different type and course of cancers. Hence, efficient quantification of VEGF is able to improve the accuracy of cancer diagnosis and precision of disease surveillance. In this research, the VEGF aptamer was designed to be able to bind with the VEGF by forming G-quadruplex secondary structures, and then the magnetic beads would capture the none-binding aptamers due to none steric interference, and finally, the fluorescence-labeled probes were hybridized with the aptamers captured by the magnetic beads. Therefore, the fluorescent intensity in the supernatant would specifically reflect the present of VEGF. After an overall optimization, the optimal conditions for detection of VEGF were as followed, KCl, 50 μM; pH 7.0; aptamer, 0.1 μM and magnetic beads, 10 μL (4 μg/μL). The VEGF could be well quantified within a range of 0.2-2.0 ng/ml in plasma, and the calibration curve possessed a good linearity (y = 1.0391x + 0.5471, r = 0.998). The detection limit (LOD) was calculated to be 0.0445 ng/mL according to the formula (LOD = 3.3×σ/S). The specificity of this method was also investigated under the appearance of many other serum proteins, and the data showed the good specificity in this aptasensor-based magnetic sensing system. This strategy provided a simple, sensitive and selective biosensing platform for detection of serum VEGF. Finally, it was expected that this detection technique can be promoted to more clinical applications.

Two 2,2':6',2''-terpyridine-based Schiff bases (TPySSB and TPySB) have been synthesized. The TPySSB shows remarkable selective ‘off-on’ fluorescence for Al³⁺ by photoinduced electron transfer (PET) mechanism of sensing. Chemosensor TPySSB binds Al³⁺ in a 1:2 ratio with an association constant 6.8×10⁵ (R²=0.98) and this 1:2 stoichiometric model is established on Job’s plot and ¹H NMR. Compared TPySSB and TPySB, it is of great importance of the existence of salicylidene unit due to its strong binding abilities of both phenol and C=N structure to the Al³⁺.

Novel multifunctional fluorescent chemosensors composed of electrospun (ES) nanofibers with high sensitivity toward pH, mercury ions (Hg²⁺), and temperature were prepared from poly(N-Isopropylacrylamide-co-N-methylolacrylamide-co-rhodamine derivative) (poly(NIPAAm-co-NMA-co-RhBN2AM)) by employing electrospinning process. NIPAAm and NMA moieties provide hydrophilic and thermo-responsive properties (absorption of Hg²⁺ in aqueous solutions), and chemical cross-linking sites (stabilization of the fibrous structure in aqueous solutions), respectively. The fluorescent probe, RhBN2AM is highly sensitive toward pH and Hg²⁺. Synthesis of poly(NIPAAm-co-NMA-co-RhBN2AM) with different compositions were carried on via free-radical polymerization. ES nanofibers prepared from sensory copolymers with a 71.1:28.4:0.5 NIPAAm: NMA: RhBN2AM ratio (P3 ES nanofibers) exhibited significant color change from nonfluorescent to red fluorescence while sensing pH or Hg²⁺, and high reversibility of on/off switchable fluorescence emission when Hg²⁺ and ethylenediaminetetraacetic acid (EDTA) were sequentially added. The P3 ES nanofibrous membranes had a higher surface-to-volume ratio to enhance their performance than did the corresponding thin films. In addition, the fluorescence emission of P3 ES nanofibrous membranes exhibited second enhancement above the lower critical solution temperature. Thus, the ES nanofibrous membranes prepared from P3 with on/off switchable capacity and thermo-responsive characteristics can be used as multifunctional sensory devise for specific heavy transition metal (HTM) in aqueous solutions.

A series of novel N-n-butyl-1,8-naphthalimide derivatives were synthesized via a three-step reaction involving nucleophilic substitution and acylation. All of the compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis, and the crystal structure of N-n-butyl-4-[N’,N’-bis(2`,4`-dichlorobenzoyl)ethylamino]-1,8-naphthalimide was determined. The π-π stacking interactions and hydrogen bonds between the two molecular core planes (naphthalimide ring) and the van der Waals forces between the flexible n-butyl groups resulted in a 3D long-chain structure. The UV-vis and fluorescence properties of the title compounds were investigated. The results indicated that the monosubstituted 1,8-naphthalimide derivatives bearing an electron-donating group on the benzene ring or a structure with a larger conjugative effect exhibited enhanced fluorescence properties.

This article presents the possibilities of using ferrite absorption material for shielding rooms with medical devices in order to additionally protect them against the limits of the electric component of the E field, which are up to 61 V/m. These values may appear in connection with the currently launched 5G system operating in the high-band frequency range, i.e. 28 GHz and 38 GHz, and may cause negative effects on the operation of medical devices. The possibilities of using ferrite absorption material for shielding rooms with medical devices were determined based on the results of measurements of the electrical properties of the ferrite material performed using two methods: the reflection method and the free space method. In the article, the complex electrical permittivity and complex magnetic permeability were determined for a ferrite plate based on measurements of the reflection coefficient and the transmission (attenuation) coefficient. The presented calculation and measurement results were used to show the properties of the ferrite material in the frequency range from 15 GHz to 45 GHz and to show the possibility of using it for shielding rooms as a material absorbing electromagnetic waves in this frequency range.

Melanoma is a type of highly malignant and metastatic skin cancer. In situ molecular imaging of endogenous levels of the melanoma biomarker tyrosinase (TYR) may decrease the likelihood of mortality. In this study we proposed the weakly fluorescent probe 1-(4-(2-(4-(dicyanomethylene)-4H-chromen-2-yl)vinyl)phenyl)-3-(4-hydroxybenzyl)urea (DCM-HBU), which releases a strong red-shifted fluorescent signal after a TYR-mediated oxidation followed by hydrolysis of the urea linkage. The large Stokes shift of the dye is owed to the recovery of the intramolecular charge transfer (ICT) effect. The resulting probe derivate shows a highly ratiometric fluorescence output. Furthermore, the simultaneous excitation by two near-infrared (NIR) photons of the released DCM-NH2 fluorophore could avoid the usual drawbacks, such as cellular absorption, autofluorescence and light scattering, due to an usually short wavelength of the excitation light on biological systems, resulting in images with deeper tissue penetration. In addition, the probe is useful for the quantitative sensing of TYR activity in vivo, as demonstrated in zebrafish larvae. This new ratiometric two photon NIR fluorescent probe is expected to be useful for the accurate detection of TYR in complex biosystems at greater depths than other one-photon excited fluorescent probes.

Novel cultivation technologies demand the adaptation of existing analytical concepts. Metabolic flux analysis (MFA) requires stable-isotope labeling of biomass-bound protein as the primary information source. Obtaining the required protein in cultivation set-ups where biomass is scarce or inaccessible due to low cell densities and cell immobilization is difficult to date. We developed a non-disruptive analytical concept for 13C-based metabolic flux analysis based on secreted protein as an information carrier for isotope mapping in the protein-bound amino acids. This "metabolic flux probe" (MFP) concept was investigated in different cultivation set-ups with a recombinant, protein-secreting yeast strain. The obtained results grant insight into intracellular protein turnover dynamics. Experiments under metabolic but isotopically nonstationary conditions in continuous glucose-limited chemostats at high dilution rates demonstrated faster incorporation of isotope information from labeled glucose into the recombinant reporter protein than in biomass-bound protein. Our results suggest that the reporter protein was polymerized from intracellular amino acid pools with higher turnover rates than biomass-bound protein. The latter aspect might be vital for 13C-flux analyses under isotopically nonstationary conditions for analyzing fast metabolic dynamics.

Conventional plaque assays rely on the use of overlays to restrict viral infection allowing the formation of distinct foci that grow in time as the replication cycle continues leading to counta-ble plaques that are visualized with standard techniques such as crystal violet, neutral red or immunolabeling. This classical approach takes several days until large enough plaques can be visualized and counted with some variation due to subjectivity in plaque recognition. Since plaques are clonal lesions produced by virus-induced cytopathic effect, we applied DNA fluores-cent dyes with differential cell permeability to visualize them by live cell imaging. We could observe different stages of that cytopathic effect corresponding to an early wave of cells with chromatin-condensation followed by a wave of dead cells with membrane permeabilization within plaques generated by different animal viruses. This approach enables an automated plaque identification using image analysis to increase single plaque resolution compared to crystal violet counterstaining and allows its application to plaque tracking and plaque reduction assays to test compounds for both antiviral and cytotoxic activities. This fluorescent real-time plaque assay sums to those next-generation technologies by combining this robust classical method with modern fluorescence microscopy and image analysis approaches for future applica-tions in virology.

2-(Adamantan-1-yl)-2H-isoindole-1-carbonitrile (1) has been identified as a neurobiological fluorescent ligand that may be used to develop receptor and enzyme binding affinity assays. Compound 1 was synthesised using an optimised microwave irradiation reaction and crystallised from ethanol. Crystallization occurred in the orthorhombic space group P212121 with unit cell parameters: a = 6.4487(12) Å, b = 13.648(3) Å, c = 16.571(3) Å, V = 1458(5) Å3, Z = 4. Density functional theory (DFT) (B3LYP/6-311++G (d,p)) calculations of 1 were carried out. Results showed that the optimised geometry is similar to the crystal structure parameters with a root-mean-squared deviation of 0.143 Å. Frontier molecular orbital energies and net atomic charges are discussed with a focus on potential biological interactions. Docking experiments within the active site of the neuronal nitric oxide synthase (nNOS) protein crystal structure were carried out and analysed. Important binding interactions between the DFT optimised structure and amino acids within the nNOS active site were identified that explain the strong NOS binding affinity reported. Fluorescent properties of 1 were studied using aprotic solvents of different polarities. Compound 1 showed the highest fluorescence intensity in polar solvents with excitation and emission values of 336 nm and 380 nm, respectively.

A surgical microscope is large in size, making portability impossible. The distance between the surgical microscope and the observation tissue is 15 to 30 cm, while the maximum adjustment range of the camera to the right and left is 30°. Therefore, surgical microscopes cause attenuation (above 58%) of the irradiation optical source owing to the long working distance. Moreover, the observation of tissue was dazzled with ambient light because the optical power source was strong (50 to 160 mW/cm2). Owing to the limited ability to adjust the camera to the right and left, a blind spot occurs with a surgical microscope. Therefore, it is difficult to clearly observe a tumor. In this study, a compact pen-type probe with a portable surgical microscope is proposed. The pen-type probe is small with a portable shape, and is capable of adjusting the working distance between itself and the observed tissue. It is also possible to adjust the viewing angle and fluorescence brightness. The proposed pen-type probe has no blind spots or optical density loss.

Astrocytes are morphological intricate cells and actively modulate the function of the brain. Through the numerous fine processes, astrocytes contact with neurons, blood vessels and other glia cells. Emerging evidence have shown that astrocytes exhibit brain-regional diversity in the morphology, transcriptome, calcium signaling and functions. However, little is known about the brain regional heterogeneity of astrocyte-astrocyte structural interaction. So far, the visualization and characterization of the morphological features for the adjacent astrocytes with high resolution has been difficult, and as a result, it is still well accepted that astrocytes in the adult brain share non-overlapped territory. In contrast, by using an approach that combines sparse viral labeling with dual-fluorescent dyes, which allows for efficient and specific labeling of adjacent astrocytes, thus enabling a comprehensive visualization of their fine processes and the degree of their territorial overlap. Our study in the hypothalamic regions revealed a marked spatial overlap among adjacent astrocytes. Additionally, we revealed the heterogeneity of astrocyte-neuron ratio across brain regions, and conducted an assessment of the photostability and labeling efficiency of fluorescent dyes used for labeling adjacent astrocytes. Our study here provides new insights for studying the morphological heterogeneity of astrocytes across the central nervous system.

Excitotoxicity related to the dysfunction of the N-methyl-d-aspartate receptor (NMDAR) has been indicated to play an integral role in the pathophysiology of multiple disease states, including neurodegenerative disorders such as Parkinson’s disease. There is a notable gap in the market for novel NMDAR antagonists, however current methods to analyze potential antagonists rely on indirect measurements of calcium flux and hazardous radioligand binding assays. Recently, a fluorescent NMDAR ligand, N-adamantan-1-yl-dimethylamino-1-naphthalenesulfonic acid, known as AM-DAN was developed by our group. Additional studies on this ligand is necessary to evaluate its potential as a biological tool in NMDAR research. Therefore, this study was aimed at conducting structural analyses, fluorescence experiments, high-accuracy NMDAR molecular modelling and NMDAR phencyclidine (PCP) site competition binding studies using AM-DAN. Results revealed that AM-DAN has appropriate structural properties, significant fluorescent ability in various solvents and is able to bind selectively and compete for the PCP-binding site of the NMDAR. Therefore, AM-DAN holds promise as a novel fluorescent ligand to measure the affinity of prospective drugs binding at the NMDAR PCP-site and may circumvent the use of radioligands.

Classical k-ratio models, e.g. ZAF and phi(rho z), used in electron probe microanalysis (EPMA) assume a homogeneous or multi-layered material structure, which essentially limits the spatial resolution of EPMA to the size of the interaction volume where characteristic x-rays are produced. We present a new model for characteristic x-ray emission that avoids assumptions on the material structure to not restrict the resolution of EPMA a-priori. Our model bases on the spherical harmonic (PN) approximation of the Boltzmann equation for electron transport in continuous slowing down approximation. PN models have a simple structure, are hierarchical in accuracy and well-suited for efficient adjoint-based gradient computation, which makes our model a promising alternative to classical models in terms of improving the resolution of EPMA in the future. We present results of various test cases including a comparison of the PN model to a minimum entropy moment model as well as Monte-Carlo (MC) trajectory sampling, a comparison of PN-based k-ratios to k-ratios obtained with MC, a comparison with experimental data of electron backscattering yields as well as a comparison of PN and Monte-Carlo based on characteristic X-ray generation in a three-dimensional material probe with fine structures.

N,N-dimethyl-4-nitroaniline (NNDM4NA, C8H10O2N2), is a superelastic and superplastic charge-transfer molecular crystal with a high molecular dipole moment, µ=7.95 D, which crystal-lizes in the acentric polar point group 2. Highly aligned poly-l-lactic acid (PLLA) polymer micro-fibers with embedded NNDM4NA nanocrystals were fabricated using the electrospinning tech-nique. The composite fibers display an extraordinarily high piezoelectric output response, where for a small stress of 5.0x103 Nm-2, an effective piezoelectric voltage coefficient of geff=3.6 VmN-1 was obtained. The fibers were found to display solid state blue fluorescence with a long (147 ns) life-time decay. Furthermore, the composite fibers exhibit an average increase of 67% on the Young modulus reaching 55 MPa, while the tensile strength reaches 2.8 MPa when compared with solely PLLA fibers. The results show that nanocrystals, from small organic molecules, with elastic and piezoelectric properties form hybrid functional 2-dimensional luminescent array which are me-chanical strong and generate high output voltages making them promising for applications in energy harvesting and as solid-state blue emitters.

Abstract: The spectral and dynamic properties of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)

Hemoconcentration membranes used in cardiopulmonary bypass require a pore structure design with high pure water permeability, and which does not allow protein adsorption and useful protein loss. However, studies on hemoconcentration membranes have not been conducted yet. The purpose of this study was to analyze three-dimensional pore structures and protein fouling before and after blood contact with capillary membranes using the tortuous pore diffusion model and a scanning probe microscope system. We examined two commercially available capillary membranes of similar polymer composition that are successfully used in hemoconcentration clinically. Assuming the conditions of actual use in cardiopulmonary bypass, we perfused these membranes with bovine blood. Pure water permeability before and after bovine blood perfusion was measured using the dead-end filtration. The scanning probe microscopy system was used for analysis. High-resolution three-dimensional pore structures on the inner surface of the membranes were observed before blood contact. On the other hand, pore structures after blood contact could not be observed due to protein fouling. The pore diameters calculated by the tortuous pore diffusion model and scanning probe microscopy were mostly similar and could be validated reciprocally. Achievable pure water permeabilities showed no difference despite protein fouling, leading to low values of albumin SC. This is due to the mechanism that protein fouling occurs on the membrane surface, while there is little internal pore blocking. Therefore, controlling the fouling is essential for membranes in medical use. These characteristics of the hemoconcentration membranes examined in this study are suitable for clinical use.

In this study, effluent water was produced through Submerged Membrane Bio-Reactor (SMBR) process, which is a simple system and decomposes organic matter contained in wastewater with biological treatment process and performs solid-liquid separation, Especially, ozone oxidation treatment process is applied to effluent water containing fluorescent whitening agent, which is a trace pollutant which is not removed by biological treatment, and influences the quality of reused water. The concentration of COD in the SMBR was 449.3 mg/ℓ-COD, and the concentration of permeate water was 100.3 mg/ℓ-COD. The removal efficiency was about 70.1%. The amount of ozone re- quired for the removal of the fluorescent whitening agent in the permeated water in SMBR was 6.67 g-O3/min, and the amount of ozone required to remove COD relative to the permeate water was calculated to remove 0.997 mg-COD for 1 mg of O3.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Lasiodiplodia theobromae, as one of the causing agents associated with Chinese hickory trunk cankers, has caused huge economic losses to the Chinese hickory industry due to its extremely strong pathogenicity. Though the biological characteristics of this pathogen and the occurrence pattern of this disease have been reported, few studies have focused on investigating the mechanisms responsible for L. theobromae survival strategies and pathogenicity. The high-quality genome data and the efficient transformation system are the basis for researching above mechanism events. In this study we sequenced and assembled L. theobromae strain LTTK16-3, and established the first protoplasmic preparation method and polyethylene glycol (PEG) -mediated genetic transformation system for L. theobromae. These genetic information and transformation methods established the foundation for the future mechanisms study of L. theobromae and set up the possibility of targeted molecular improvements for Chinese hickory canker control.

The energy, momentum and the action associated with the time domain transition radiation fields are investigated. The results show that for a charged particle moving with speed $v$, the longitudinal momentum associated with the transition radiation is approximately equal to $E/c$ for values of $1-v/c$ smaller than about 10^-3 where $E$ is the total radiated energy and c is the speed of light in free space. The action of the transition radiation, defined as the product of the energy dissipated and the duration of the emission, increases as $1-v/c$ decreases and, for an electron, it becomes equal to $h/4\pi$ when $v=c-v_m$ where $v_m$ is the speed associated with the lowest energy state of a particle confined inside the universe and h is the Plank constant. Combining these results with Heisenberg’s uncertainty principle, an expression for the electronic charge based on other fundamental physical constants is derived. The best agreement between the experimentally observed electronic charge and the theoretical prediction is obtained when one assumes that the actual size of the universe is about 250 times larger than the visible universe.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

Rationale - From the year 1 anno Domini until 1855 with the third Plague, major pandemics occurred on average every 348 years. Since then, they have occurred on average every 33 years, with Coronavirus disease 2019 (COVID-19) now underway.Even though current technologies have greatly improved the way of life of human beings, COVID-19, with more than 700 000 000 cases and 6 950 000 deaths worldwide by the end of 2023, reminds us that much remains to be done. Objective - Given the frequency and duration of recent pandemics, it might be wise to start thinking about preventative methods to minimize the impact of future pandemics. This report looks back at 18 months of COVID-19, from March 2020 to August 2021, with the aim of highlighting potential solutions that could prove practical, or even essential, for the future. Material - COVID-19 data, including case and death reports, were extracted daily from the Worldometer platform to build a database for macroscopic analysis of the spread of the virus around the world. Demographic data were integrated into the COVID-19 database for a better understanding of the spatial spread of the SARS-CoV-2 virus in cities/municipalities. Method - Without loss of generality, we only analyzed data from the top 30 (out of 200 and above) countries ranked by total number of COVID-19 cases. Statistics (regression, t-test (p < 0.05), correlation, mean ± std, etc.) were carried out with Excel software. Spectral analysis, using Matlab software, was also used to try to better understand the temporal spread of COVID-19. Results - A good linear correlation was observed between the number of cases and the respective number of deaths depending on the country, i.e. y = 0.0121x + 19559 with R² = 0.8042. The analysis then focused mainly on the number of cases.This study showed that COVID-19 mainly affects G20 countries. The most interesting result is that cities/municipalities with high population density are a powerful activator of the spread of the virus. The current demographic context seems to be becoming a societal problem that must be addressed adequately.Spectral analysis highlighted that the very first months of spread of COVID-19 were the most notable with a strong expansion of the SARS-CoV-2 virus. On the other hand, the following six months showed a certain stability due mainly to multiple preventive measures such as confinement, closure of non-essential services, wearing of masks, distancing of 2 meters, etc. Discussion - Analysis of case and death data showed that COVID-19 mainly affects G20 countries. Nevertheless, the most interesting result of this study is that cities and municipal areas with population densities of several thousand inhabitants per square kilometer largely favored the spread of the SARS-CoV-2 virus. It is believed that such a demographic context is becoming a societal problem that developed countries around the world will sooner or later face and therefore needs to be adequately addressed. Conclusion - COVID-19 has made us understand that it is time to act both preventatively and curatively. Phenomenological insights suggest that the next pandemic could occur in less than 50 years. It may be time to launch new societal projects aimed at relieving congestion in densely populated regions.

Protein Kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement of PKCδ for preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ selectively deletes anti-dsDNA B cells in the germinal center (GC), disclosing a key B cell tolerance mechanism that prevents lupus autoimmunity. PKCδ’s tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ’s tolerance activity, and discuss the potential significance of therapeutically targeting PKCδ’s tolerance activity in the GC for selectively inhibiting lupus autoimmunity.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both hereditary and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variations that can be transmitted from one generation to another can be a significant contributor to causing family or isolated DCM. Genetic variation also plays a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a diverse range of phenotypic expressions. It is crucial to select the most probable patients to have advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the crucial relationships between genotype and phenotype, and the usefulness of genetic testing in the therapeutic care of both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

Fast Field-Cycling (FFC) Nuclear Magnetic Resonance (NMR) relaxometry is a powerful non-destructive magnetic resonance technique that enables, among other things, the investigation of slow molecular dynamics at low magnetic field intensities. FFC-NMR relaxometry measurements provide insight into molecular motion across various timescales within a single experiment. This study focuses on a \textit{model-free} approach, representing the NMRD profile $R_1$ as a linear combination of Lorentzian functions, thereby addressing the challenges of fitting data within an ill-conditioned linear least-squares framework. Tackling this problem, we present a comprehensive review and experimental validation of three regularization approaches to implement the model-free approach to analysing NMRD profiles. These include: (1) \nameUpe, utilizing locally adapted $L_2$ regularization; (2) \nameL, based on $L_1$ penalties; and (3) a hybrid approach combining locally adapted $L_2$ and global $L_1$ penalties. Each method's regularization parameters are determined automatically, according to the Balancing and Uniform Penalty principles. % Our contributions include the implementation and experimental validation of the \nameUpe{} and \nameUp{} algorithms, and the development of a "dispersion analysis" technique to assess the existence range of the estimated parameters. The objective of this work is to delineate the variance in fit quality and correlation time distribution yielded by each algorithm, thus broadening the set of software tools for the analysis of sample structures in FFC-NMR studies. The findings underline the efficacy and applicability of these algorithms in the analysis of NMRD profiles from samples representing different potential scenarios. 1

Preterm infants have increased body adiposity at term equivalent age and risk for adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

Scattering of a probe laser pulse by an intense light spring in QED vacuum is considered. This new scattering configuration can be seen as the vacuum equivalent to the process originally associated with scattering of light by a rotating black hole, usually called Penrose superradiance. Here the rotating object is an intense laser beam containing two different components of orbital angular momentum. Due to these two components with slightly different frequencies, the energy profile of the intense laser beam rotates with a frequency that depends on the frequency difference. The nonlinear properties of quantum vacuum are described by first order Euler-Heisenberg Lagrangian. It is shown that, in such a configuration, nonlinear photon-photon coupling leads to scattered radiation, with frequency shift and angular dispersion. These two distinct properties, of frequency and propagation direction, could eventually be favourable for possible experimental observations. In principle, this new scattering configuration can also be reproduced in a nonlinear optical medium.

Polyphenols are the most common organic compounds in wine. They improve both the sensory aspects of wine and human health by activating antioxidant systems. Therefore, there is a great need for a simple, fast and accessible method to determine the polyphenol content of wine. The aim of this study is to characterize polyphenolic compounds in natural wine samples using an electrochemical method and a modified carbon paste electrode with TiO2 nanoparticles. This work is motivated by the promising improvement of the sensing properties of a TiO2 nanoparticle-modified carbon paste electrode observed in the electrooxidation of different polyphenols. Since the voltammetric response of wine is largely irreversible, another motivation was the possibility of improving the processing of voltammograms to obtain data indicative of wine polyphenols, based on the approach described in the seminal work by Espinoza et al. The modified electrode studied provides an improved and reproducible voltammetric response of gallic acid in wine samples and provides a good basis for further development of an integrated sensor/data system with the possibility of wider application for the quantification of gallic acid as a flavor and visually relevant parameter in winemaking.

Previous studies reported a reduction of the perceived effort and an improvement of the perfor-mances of healthy subjects and patients when a motor task was combined with artistic images with respect to non-artistic images. This phenomenon, called Michelangelo effect, could contribute to the efficacy of art therapy in neurorehabilitation. In this study, the possible occurrence of this effect was tested in a cognitive task by asking to 15 healthy subjects and 17 patients with stroke to solve a digital version of the classical memory card game. Three different types of images were used in a randomized order: French cards, artistic portraits, and photos of famous people (to compensate the possible effects of face recognition). Healthy subjects were involved to test the usability and the load demanding of the developed system, reporting no statistically significant differences among the three sessions (p > 0.05). Conversely, patients had a better performance in terms of time (p = 0.014) and number of trials (p = 0.007) needed to complete the task in presence of artistic stimuli, accompanied by a reduction of the perceived effort (p = 0.033). Furthermore, artistic stimuli, with respect to the other two types of images, seemed more associated to visuo-spatial control than to linguistic functions.

Apple replant disease (ARD) is a complex issue caused by various fungal, oomycetes pathogens and parasites which can differ in their abundance between sites within a geographic region. Knowledge of the specific etiology of ARD at a particular site is required in order to develop commercially viable soil management strategies to combat specific/individual components of the disease. In this study we analyzed the soil from six ARD sites for the presence of fungal, bacterial and oomycetes communities and plant parasitic nematodes. Five fungal, and 17 bacterial classes were differentially represented in the microbiomes from different locations. Mortierellomycetes was the most abundant fungal taxa represented followed by Sordariomycetes. Mortierella exigua a fungal endophyte was the most abundant fungal amplicon sequence variant (ASV) in the core microbiome. Proteobacteria was the most prevalent phylum identified in orchard soils. Several potential phytopathogenic fungi involved in ARD and endophytes including Fusarium oxysporum, F. solani, Nectria ramulariae, Ilyonectria robusta and Nectriaceae were identfied in the orchard soil. Pythium attrantheridium (Globisporangium attrantheridium), P. monospermum and P. ultimum (Globisporangium ultimum) were the most abundant oomycete taxa identified in these soil samples. Six different groups of plant-parasitic nematodes were found across the six orchards soil. Root-lesion nematodes, Pratylenchus spp., which are commonly associated with ARD, were identified in all orchards soil at population densities ranging from 12 to 33/100 cm3 soil. This research contributes valuable understanding of the ARD complex as the apple industry needs alternative approaches to combat the disease.

The main focus of this review is to introduce readers to the fascinating class of lipid molecules known as norsteroids, exploring their distribution across various biotopes and their biological activities. The review provides an in-depth analysis of various modified steroids, including A, B, C, and D-norsteroids, each characterized by distinct structural alterations. These modifications, which range from the removal of specific methyl groups to changes in the steroid core, result in unique molecular architectures that significantly impact their biological activity and therapeutic potential. The discussion on A, B, C, and D-norsteroids sheds light on their unique configurations and how these structural modifications influence their pharmacological properties. The review also presents examples from natural sources that produce a diverse array of steroids with distinct structures, including the aforementioned A, B, C, and D-nor variants. These compounds, sourced from marine organisms like sponges, soft corals and starfish, as well as terrestrial entities such as plants, fungi, and bacteria. The exploration of these steroids encompasses their biosynthesis, ecological significance, and potential medical applications, highlighting a crucial area of interest in pharmacology and natural product chemistry. The review emphasizes the importance of researching these steroids for drug development, particularly in addressing diseases where conventional medications are inadequate or for conditions lacking sufficient therapeutic options. Examples of norsteroid synthesis are provided to illustrate the practical applications of this research.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Generative artificial intelligence (GenAI) has been developing with many incredible achievements like ChatGPT and Bard. Deep generative model (DGM) is a branch of GenAI, which is preeminent in generating raster data such as image and sound due to strong points of deep neural network (DNN) in inference and recognition. The built-in inference mechanism of DNN, which simulates and aims to synaptic plasticity of human neuron network, fosters generation ability of DGM which produces surprised results with support of statistical flexibility. Two popular approaches in DGM are Variational Autoencoders (VAE) and Generative Adversarial Network (GAN). Both VAE and GAN have their own strong points although they share and imply underline theory of statistics as well as incredible complex via hidden layers of DNN when DNN becomes effective encoding/decoding functions without concrete specifications. In this research, VAE and GAN is unified into a consistent and consolidated model called Adversarial Variational Autoencoders (AVA) in which VAE and GAN complement each other, for instance, VAE is good at generator by encoding data via excellent ideology of Kullback-Leibler divergence and GAN is a significantly important method to assess reliability of data which is realistic or fake. In other words, AVA aims to improve accuracy of generative models, besides AVA extends function of simple generative models. In methodology this research focuses on combination of applied mathematical concepts and skillful techniques of computer programming in order to implement and solve complicated problems as simply as possible.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

Background/Objectives: Population aging is rapidly increasing, and the importance of preventive medicine has been stressed. Health checkup, diet, and exercise are of paramount importance. This study aimed to evaluate the effectiveness of a personalized dual-task intervention that combined exercise with cognitive tasks in improving physical and cognitive functions among independently living elderly individuals. Methods: Participants were aged &gt;65 years who were mostly independent in their activities of daily living, divided into 2 groups. The group receiving the 20-min robot-assisted session was compared to the group receiving traditional functional restoration training. This randomized trial assessed the impact of this intervention on the 30-s chair stand test score and Montreal Cognitive Assessment-Japanese version score of the participants. Results: Both scores significantly improved in the intervention group, indicating enhanced lower-limb function and cognitive capabilities. Conclusions: These findings suggest that integrating cognitive tasks with physical exercise can be a potent strategy to improve overall well-being in the elderly, offering valuable insights for designing comprehensive preventive health programs tailored to this demographic.