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We report the construction of a mouse-human (M-H) heterohybridoma by fusion of the murine myeloma cell line NS-1 and human spleen cells from a 17 week old fetus. The nonsecreting, cloned hybridoma cell line II was resistant to 8-azaguanine (8-AG) and sensitive to hypoxanthine, aminopterin and thymidine (HAT) medium. It grew rapidly in 8-AG containing medium (doubling time 20 hrs.), but did not grow in HAT medium or in non-serum medium. It had a high fusion frequency with human lymphocytes from regional lymph nodes. Five human chromosomes were retained stably for over 6 months by this cell line II. Nine (mouse-human)-human ((M-H)-H) triple hybridomas secreting human IgG 1 or IgM were established by the fusion of this parental cell line II and human lymphocytes from regional lymph nodes. Immunoglobulin secretion was stable and has been maintained for over 8-10 months without recloning in these hybridomas. Secretion of immunoglobulin varies from 2.1-3.0 micrograms/10(6) cells/day, and these hybridomas contain from 3 to 16 human chromosomes, including No. 14. So, this M-H heterohybridoma II is an excellent useful parental cell line for the production of hybridomas secreting human immunoglobulin.

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery. [ABSTRACT FROM AUTHOR]

Noncoding RNAs instruct the Cas9 nuclease to site-specifically cleave DNA in the CRISPR/Cas9 system. Despite the high incidence of hepatocellular carcinoma (HCC), the patient's outcome is poor. As a result of the emergence of therapeutic resistance in HCC patients, clinicians have faced difficulties in treating such tumor. In addition, CRISPR/Cas9 screens were used to identify genes that improve the clinical response of HCC patients. It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer, with a particular emphasis on HCC as part of the current state of knowledge. Thus, in order to locate recent developments in oncology research, we examined both the Scopus database and the PubMed database. The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs. Drug resistance can be overcome with the help of the CRISPR/Cas9 system. HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening, although this method is not without limitations. It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy. CRISPR and its applications to tumor research, particularly in HCC, are examined in this study through a review of the literature. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain–gut–liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain–gut–liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines. [ABSTRACT FROM AUTHOR]

Various defects are produced during the laser powder bed fusion (L-PBF) process, which can affect the quality of the fabricated part. Previous studies have revealed that the defects formed are correlated with molten pool dimensions. Powder particles are thinly spread on a substrate during the L-PBF process; hence, powder packing properties should influence the molten pool dimensions. This study evaluated the influence of particle size on powder packing properties and molten pool dimensions obtained through numerical simulations. Using particles with different average diameters ( D a v ) of 24, 28, 32, 36, and 40 μ m, a series of discrete-element method (DEM) simulations were performed. The packing fraction obtained from DEM simulations became high as D a v became small. Several particles piled up for small D a v , whereas particles spread with almost one-particle diameter thickness for large D a v . Moreover, the packing structure was inhomogeneous and sparse for large D a v . As a result of multiphysics computational fluid dynamics (CFD) simulations incorporating particles' positions as initial solid metal volume, the molten pool width obtained was hardly dependent on the D a v and was roughly equivalent to the laser spot size used in the simulations. In contrast, the molten pool depth decreased as D a v decreased. Even if the powder bed thickness is the same, small particles can form a complex packing structure by piling up, resulting in a large specific surface area. This can lead to a complex laser reflection compared to the large particles coated with almost one-particle thickness. The complex reflection absorbs the heat generated by laser irradiation inside the powder bed formed on the substrate. As a result, the depth of the molten pool formed below the substrate is reduced for small particles. [ABSTRACT FROM AUTHOR]

Thermocatalytic decomposition is an efficient purification technology that is potentially applicable to degrading chemical warfare agents and industrial toxic gases. In particular, ZrO2 has attracted attention as a catalyst for the thermocatalytic decomposition of dimethyl methylphosphonate (DMMP), which is a simulant of the nerve gas sarin. However, the influence of the crystal phase and morphology on the catalytic performance of ZrO2 requires further exploration. In this study, monoclinic- and tetragonal-phase ZrO2 (m- and t-ZrO2, respectively) with nanoparticle, flower-like shape and hollow microsphere morphologies were prepared via hydrothermal and solvothermal methods, and their thermocatalytic decomposition of DMMP was systematically investigated. For a given morphology, m-ZrO2 performed better than t-ZrO2. For a given crystalline phase, the morphology of hollow microspheres resulted in the longest protection time. The exhaust gases generated by the thermocatalytic decomposition of DMMP mainly comprised H2, CO2, H2O and CH3OH, and the by-products were phosphorus oxide species. Thus, the deactivation of ZrO2 was attributed to the deposition of these phosphorous oxide species on the catalyst surface. These results are expected to help guide the development of catalysts for the safe disposal of chemical warfare agents. [ABSTRACT FROM AUTHOR]

About 40% of cedar pollinosis patients living in the Yamagata Prefecture showed pollinosis symptoms before the first day of the pollen season, which was determined by Durham samplers, the standard sampler for pollen information in Japan. The amount of Cry j 1 (major cedar pollen allergen) per cedar pollen is reported to be six pg. This amount is difficult to measure using the ELISA method, so we applied the highly sensitive ESR radical immunoassay method to measure the allergen; now we can provide information for sensitive patients. It revealed that Cry j 1 exists in orbicles and tapetum. It is presumed that it is smaller than pollen, so it comes from a place where cedar are already in bloom. It is desirable to obtain real-time information on an hourly basis. Currently, information from automatic cedar pollen monitors is becoming main-stream. However, this monitor may count during snowfalls, Asian dust flying, etc., even when there was no apparent pollen examined with a microscope. This paper describes the current status of automatic cedar pollen monitors, their usefulness, and their advantages and disadvantages in comparison with results obtained by other methods of measurement. Lastly, the paper describes expectations for cedar pollen information in the future. [ABSTRACT FROM AUTHOR]

Preheating is important to improve the mechanical properties of nickel-based superalloys processed by additive manufacturing. The microstructure of IN718 was found to be influenced by the preheating temperature. Different preheating temperatures affect mechanical properties by changing microstructures. This work aims to clarify the thermal behavior for two preheated base plate temperatures (200 °C and 600 °C) on the IN718 superalloy built by the selective laser melting (SLM) process using the finite element method and experiments. The simulation findings indicate that the preheated 600 °C model has a deeper melt pool, a slower transformation of liquid to solid, and a slower cooling rate compared to the 200 °C model. As a result, the interdendritic Niobium (Nb) segregation of IN718 is reduced, thus improving the mechanical properties of additive-manufactured IN718 using the laser. The solidification map derived from the simulation indicates a columnar microstructure for the IN718 superalloy. Preheating increased the size of the dendrite structure and reduced elemental segregation, but it did not affect the morphology or size of crystal grains. We focused on comparing the temperature gradient and cooling rate for the two preheated base plate temperatures using the solidification map of IN718. The simulation confirmed that preheating does not affect the grain structure. [ABSTRACT FROM AUTHOR]

A miniaturized electrochemical sensor was developed for the remote detection of chemical warfare agent (CWA) simulants. To facilitate drone-based remote sensing, this present study focuses on advancing the miniaturized and compact electrochemical sensor for monitoring two CWA simulants, diisopropyl fluorophosphate (DFP) and O,S-diethylmethylphosphonothioate (O,S-DEMPT). The differential pulse voltammetry (DPV) signal was processed, and the DPV signature features were extracted on the basis of the redox properties associated with the absence and the presence of DFP and O,S-DEMPT. Upon the addition of 0.10 equivalence of DFP or O,S-DEMPT, a shift in potential (E) of ~0.13 V was recorded. The limit of detection (LOD) was calculated to be 0.25 µM (0.046 ppm) and 0.10 µM (0.017 ppm) for DFP and O,S-DEMPT, respectively. These results were validated using a portable Palmsens Emstat HR potentiostat, which corroborated the results obtained using a lab benchtop potentiostat. Additionally, Boolean logic ("AND" operation) was implemented for future drone technology deployment. This advancement enables the fabrication of a networked device capable of autonomously executing tasks without constant oversight. [ABSTRACT FROM AUTHOR]

Condensation reactions between some SH-amino acids (L-and D-cysteine 1%) and acetaldehyde (50 microM) were studied in vitro experiment. In the aqueous solution, free acetaldehyde was reduced to 41.3% by L-cysteine and to 36.4% by D-cysteine. In the reaction with human blood medium, after the medium was deproteinized with perchloric acid reagent, acetaldehyde was reduced to 47.0% by L-cysteine and to 43.8% by D-cysteine. D-Cysteine appears to have great stability of reacting acetaldehyde. In vitro experiment reactability for D-cysteine exhibited 3-8% higher than that for L-cysteine. Next, effects of some amino acids on alcohol metabolism were studied in male ICR mice. The animals were given ethanol through a gastric catheter at a dose of 2 g/kg and they were intraperitoneally injected L-cysteine (300 mg/kg), D-cysteine (300 mg/kg), L-alanine (300 mg/kg) and control (saline), respectively in the period of one hour before the injection of ethanol. Blood and tissues samples were analyzed for ethanol, acetaldehyde, acetate and acetone during alcohol intoxication in mice by head space gas chromatography. In the groups administered D-cysteine and L-cysteine, the mice showed a definitely faster oxidation and disappearance of ethanol. Especially in the D-cysteine group, ethanol levels in blood, liver and brain remained lower than that in the other groups (p less than 0.01). Acetaldehyde levels in blood, liver and brain remained low by L-cysteine. Ethanol metabolites during alcohol oxidation by chemical reactabilities of L- and D-cysteine showed different distribution in the mice, respectively. In the mice received L-alanine, acetate and acetone levels in blood, liver and brain were distinctly reduced (p less than 0.01). L-Alanine is reported to supply an abundance of pyruvic acid that performs the NAD-generating system. NAD produced is introduced to alcohol metabolism and the TCA cycle. It was thus presumed that the L- or/and D-cysteine, and L-alanine was effective in acute alcohol intoxication by heavy drinking.

We developed a sandwich enzyme-linked immunosorbent assay (ELISA) system for calphobindin I (CPB-I), a new placental coagulation inhibitor, using two monoclonal antibodies. This ELISA system can detect CPB-I at concentrations of between 0.4 and 25 ng/ml in buffer and allow almost quantitative determination of it in human plasma. Using this ELISA system, CPB-I levels in many kinds of specimens were measured. Levels in the plasma and urine of women were as low as 10 ng/ml, and no significant differences were observed throughout the trimesters of pregnancy and during different stages of the menstrual cycle. Toxemic patients were slightly higher in CPB-I levels than normal pregnant women, and levels in body fluids such as the amniotic fluid, saliva, milk, ascites, and semen were higher than those in the plasma. The high levels of CPB-I were found, being in the order of micrograms/ml, in the ascites of carcinomatous peritonitis as well as seminal plasma. Measurements of the levels in ovarian follicular fluid samples at different stages of the menstrual cycle showed that those in the immature and atretic stages were higher than those in mature stages. CPB-I levels in many types of cultured human cells ranged from 0.023 to 10.30 micrograms/mg protein, and levels in cultured human lymphocytes were less than those in other types of cells measured. Little of this inhibitor was secreted into media from cultured human lymphocytes, and it was found in all measured tissues of Macacus irus at levels ranging from 0.232 to 1.557 micrograms/mg protein. From these results, it was suggested that CPB-I might be a ubiquitous protein in the body that has an important physiological role.

The nervous system significantly participates in maintaining homeostasis, and modulating repair and regeneration processes in the liver. Moreover, the nervous system also plays an important role in the processes associated with the development and progression of liver disease, and can either potentiate or inhibit these processes. The aim of this review is to describe the mechanisms and pathways through which the nervous system influences the development and progression of liver diseases, such as alcohol-associated liver disease, nonalcoholic fatty liver disease, cholestatic liver disease, hepatitis, cirrhosis, and hepatocellular carcinoma. Possible therapeutic implications based on modulation of signals transduction between the nervous system and the liver are also discussed., (© 2024 Japan Society of Hepatology.)

Background and Objectives: A recent Japanese phase three clinical trial for lung cancer suggested a possible advantage of segmentectomy over lobectomy in terms of death from other diseases. This study aimed to compare the risk of death from other diseases based on surgical procedures in lung cancer patients without recurrence., Methods: We retrospectively reviewed 2121 patients without disease recurrence after curative resection for lung cancer at our institution. Patient characteristics and overall survival were compared between sublobar resection and lobectomy., Results: The sublobar group (n = 595) had a significantly higher proportion of women, non-smokers, patients without comorbidities, patients with a history of other cancers, and patients with earlier-staged disease when compared with the lobectomy group (n = 1526). The overall survival was significantly longer in the sublobar group than in the lobectomy group (p = 0.0034). After adjusting for background characteristics in an analysis of 488 patients, the overall survival had a trend to be longer in the sublobar group than in the lobectomy group (p = 0.071)., Conclusions: Our results suggested that the risk of death from other diseases was potentially higher after lobectomy than after sublobar resection. Although several clinical factors could influence the results, these results may support the benefit of sublobar resection, assuming that the curability of both procedures is similar., (© 2024 Wiley Periodicals LLC.)

Ghrelin widely exists in the central nervous system and peripheral organs, and has biological activities such as maintaining energy homeostasis, regulating lipid metabolism, cell proliferation, immune response, gastrointestinal physiological activities, cognition, memory, circadian rhythm and reward effects. In many benign liver diseases, it may play a hepatoprotective role against steatosis, chronic inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress and apoptosis, and improve liver cell autophagy and immune response to improve disease progression. However, the role of Ghrelin in liver Echinococcosis is currently unclear. This review systematically summarizes the molecular mechanisms by which Ghrelin regulates liver growth metabolism, immune-inflammation, fibrogenesis, proliferation and apoptosis, as well as its protective effects in liver fibrosis diseases, and further proposes the role of Ghrelin in liver Echinococcosis infection. During the infectious process, it may promote the parasitism and survival of parasites on the host by improving the immune-inflammatory microenvironment and fibrosis state, thereby accelerating disease progression. However, there is currently a lack of targeted in vitro and in vivo experimental evidence for this viewpoint. [ABSTRACT FROM AUTHOR]

Assuming a delta pulse excitation, quantum wavepackets are propagated on the excited state manifold in the energy range from 3.4–5.0 eV for coronene and 2.4–3.5 eV for circumcoronene to study the time evolution of the states as well as their lifetimes. The full-dimensional (102 and 210 degrees of freedom for coronene and circumcoronene respectively) non-adiabatic dynamics simulated with the ML-MCTDH method on twelve coupled singlet electronic states show that the different absorption spectra are only due to electronic delocalisation effects that change the excited state energies, but the structural dynamics in both compounds are identical. Breathing and tilting motions drive the decay dynamics of the electronic states away from the Frank–Condon region independently of the size of the aromatic system. This promising result allows the use of coronene as a model system for the dynamics of larger polycyclic aromatic hydrocarbons (PAHs) and graphene one dimensional sheets or nanoflakes. [ABSTRACT FROM AUTHOR]

To respond to the constant miniaturization of modern devices, it is imperative to develop novel classes of hybrid materials with outstanding functionalities. One of the most promising developments in this regard is photoswitchable nanoelectronics, which offer non-invasive structural changes via irradiation. Azobenzenes, in particular, represent a widely investigated group of compounds due to their reversible photoisomerization and flexibility to introduce modifications by functionalizing the aryl ring. Here, an interface consisting of graphene quantum dots (GQDs) and a pyrene functionalized azobenzene (AZO) is built and investigated to unravel the energy and charge transfer dynamics at play. The influence of the conformation, isomerization and thermal effects on the photophysics is described using a multiscale computational approach coupled to electronic structure calculations. By computing the photoinduced energy and charge transfer rates we found that the small exciton reorganization energy and favorable alignment of the energy levels at the interface favor excitation energy transfer. A significant increase of photoinduced hole transfer from AZO to GQDs is observed when thermal effects are considered. Moreover, these photoinduced processes for the azobenzene molecules in their trans configuration are always faster than those related to the cis isomer. This is due to a favorable overlap and a stronger interaction of the trans isomer, considered the active state, with the GQDs. On the other hand, the cis configuration, featuring slower photoinduced energy and charge transfer processes, can be considered as the inactive species. Nevertheless, its contribution to the overall photophysics remains non-negligible. [ABSTRACT FROM AUTHOR]

The adverse effects of urbanized areas' growth might be mitigated by the multiple ecosystem services that urban green infrastructure provides. However, the design and composition of such infrastructure is still a hotly debated issue, mainly considering the challenges associated with the use of exotic plant species. To assess if there is a clear association between the species' origin and ecosystem services or ecosystem disservices, an in-depth systematic literature review was carried out based on a bibliometric approach to assess the panorama of the scientific perspective. Based on the results, a detailed analysis was performed for the urban green infrastructure of five European Mediterranean cities, where management and expansion of the urban green infrastructure might act as tools to mitigate climate change and biodiversity loss. Urban green infrastructure benefits to urban areas and its composition must consider the balance between services and disservices provided by plant species. Data analysis shows that disservices are not exclusively related to exotic species, revealing that plant species selection based on their origin represents a biased approach, as it often disregards the higher capacity of some exotic species to thrive under continuous pressure and disturbance, along with relevant and highly valued cultural services provided. Since exotic species are commonly used, ecosystems formed can be seen as experiments to support decisions, allowing new approaches to planning, designing, and maintaining urban green infrastructure. [ABSTRACT FROM AUTHOR]

Dielectric barrier discharge (DBD)-based technology is considered a promising alternative for controlling indoor air pollutants. However, its limited processing capacity and lack of design techniques have restricted its use in practical applications. This paper introduces a methodology for designing upscaled DBD reactors with a processing capacity of up to 1000 L/min for treating high-flow-rate gases to mitigate indoor air pollution. A ten-layer high-flow-rate DBD reactor was constructed, with fundamental characterizations, including electrical and spectroscopic measurements, conducted to verify the feasibility of the proposed methodology. In particular, the flow paths of the ten-layer DBD reactor were optimized by incorporating an air diffuser and perforated metal plates, all without significant modifications. Computational fluid dynamics simulations showed a remarkably improved velocity uniformity (0.35 m/s to 0.04 m/s, as evidenced by the velocity standard deviation) in the 10 flow channels. These simulation results were consistent with the experimental results, wherein the velocity standard deviation reduced from 1.38 m/s to 0.13 m/s. Moreover, multi-gas plasma ignition for up to six gas species and high-flow-rate plasma generation of up to 1000 L/min were achieved. These results provide the foundation for developing DBD technologies for practical applications in high-flow-rate gas treatment, particularly for controlling indoor air pollution. [ABSTRACT FROM AUTHOR]

Multicolor emissive carbon dots (CDs) hold great potential for a wide range of applications in various fields. However, the luminescence enhancement mechanism is still controversial due to combined effects of the carbon core and surface states. Herein, we elucidate the surface state mechanism for the tunable and enhanced photoluminescence of CDs via only surface nitrogen and sulfur modification (N,S-CDs) through an electrochemical synthesis method. It is demonstrated that surface nitrogen functionalization with increasing content of NH2 groups leads to multicolor emission from blue to red. Moreover, surface sulfur functionalization with the introduction of C–S bonds can further improve the luminescence intensity by facilitating the transition of S-related excitation electrons and radiative recombination. In addition, the high luminance of N,S-GCDs enables their application in flexible fluorescence films, latent fingerprint detection and information encryption. [ABSTRACT FROM AUTHOR]

A molecular imprinted polymer (MIP) fabricated from a chitosan doped with graphite to create a conductive composite (CG-MIC) with the ability to trap and detect dimethyl methylphosphonate (DMMP) through a change in resistance of the material has been successfully manufactured. The GC-MIC presented a maximum trapping capacity of 96 ppm (0.096 mg g−1) of DMMP. A similar non-imprinted composite made of chitosan-graphite (CG-NIC) had a surface adsorption of 48 ppm (0.048 mg g−1) of DMMP. The manufacturing process was tested for consistency and there were no significant differences in resistance between batches of CG-MIC before (around 450 Ω) and after (around 70 Ω) DMMP extraction, representing a homogeneous manufacturing process. Although Atomic Force Microscopy studies revealed that the graphite was not homogenously distributed throughout the chitosan matrix, the response was consistent. The changes in the concentration of DMMP within the self-sensing material, being proportional to those in gas concentration, could be followed by the changes in resistance. The inclusion of common interferents: Acetic acid, acetone, ethanol, ammonium hydroxide and 2-propanol, equivalent in concentration to the DMMP, caused a change in the resistance of the material but did not substantially affect the specific resistance response of the composite material. Based on this data, the CG-MIC could be used as a smart material with sensing capabilities to monitor trapping levels of DMMP. [ABSTRACT FROM AUTHOR]

The most favorable targets for retrospectively determining human exposure to organophosphorus pesticides, insecticides, retardants, and other industrial organophosphates (OPs) are adducts of OPs with blood plasma butyrylcholinesterase (BChE) and human serum albumin (HSA). One of the methods for determining OP exposure is the reactivation of modified BChE using a concentrated solution of KF in an acidic medium. It is known that under the action of fluoride ion, OPs or their fluoroanhydrides can be released not only from BChE adducts but also from the adducts with albumin; however, the contribution of albumin to the total pool of released OPs after plasma treatment with KF has not yet been studied. The efficiency of OP release can be affected by many factors associated with the experimental technique, but first, the structure of the adduct must be taken into account. We report a comparative analysis of the structure and conformation of organophosphorus adducts on HSA and BChE using molecular modeling methods and the mechanism of OP release after fluoride ion exposure. The conformational analysis of the organophosphorus adducts on HSA and BChE was performed, and the interaction of fluoride ions with modified proteins was studied by molecular dynamics simulation. The geometric and energy characteristics of the studied adducts and their complexes with fluoride ion were calculated using molecular mechanics and semiempirical approaches. The structural features of modified HSA and BChE that can affect the efficiency of OP release after fluoride ion exposure were revealed. Using the proposed approach, the expediency of using KF for establishing exposure to different OPs, depending on their structure, can be assessed. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteoarthritis is a common complex disease, which affects the whole joint and causes disability in millions of patients. Currently, there is no cure for this disease; there is only the possibility of symptomatic therapy. Due to this, animal models play an important role in further investigating the pathophysiology and developing therapeutic strategies. The turquoise killifish, Nothobranchius furzeri, is a well-known model for the investigation of the effects of fast aging, that spontaneously develops spinal deformities. The aim of this study was to investigate the characteristics of the intervertebral discs of healthy and deformed N. furzeri, which have never been described before. Our study shows age- and disease-related alterations in the vertebral discs of N. furzeri. Introduction: Osteoarthritis is a classical age-related disease, which affects millions of patients worldwide. To further understand the pathophysiology and to develop therapeutic strategies for this disease, animal models play a significant role. Nothobranchius furzeri is an established model for accelerated aging that spontaneously develops spinal deformities. Although the bone properties of N. furzeri are well described, characteristics of the intervertebral discs are still unknown. The aim of this study was to investigate the characteristics of the intervertebral discs of healthy and deformed N. furzeri. Material and Methods: Intervertebral properties of healthy and deformed N. furzeri were investigated in 8-, 12-, 18- and 21.5-week-old male fish of the GRZ strain. For histological evaluations the fish were decalcified, paraffin-embedded and stained with (1) hematoxylin and eosin, (2) toluidine blue and (3) alcian blue/picrosirius red. Results: 8-week-old and deformed N. furzeri showed spongy-like tissue containing vacuolated notochord cells and a beginning formation of fibrous tissue in the central area. Older healthy fish showed fibrous tissue in the central region and a spongy-like tissue in the peripheral region. Conclusion: Our study revealed age- and disease-related alterations of the vertebral discs in N. furzeri. Further studies should investigate the utility of N. furzeri as a model for degenerative spine diseases. [ABSTRACT FROM AUTHOR]

Metabolic‑associated fatty liver disease (MAFLD) is the most common chronic liver disease. Gut dysbiosis is considered a significant contributing factor in disease development. Increased intestinal permeability can be induced by gut dysbiosis, followed by the entry of lipopolysaccharide into circulation to reach peripheral tissue and result in chronic inflammation. We reviewed how microbial metabolites push host physiology toward MAFLD, including short‑chain fatty acids (SCFAs), bile acids, and tryptophan metabolites. The effects of SCFAs are generally reported as anti‑inflammatory and can improve intestinal barrier function and restore gut microbiota. Gut microbes can influence intestinal barrier function through SCFAs produced by fermentative bacteria, especially butyrate and propionate producers. This is achieved through the activation of free fatty acid sensing receptors. Bile is directly involved in lipid absorption. Gut microbes can alter bile acid composition by bile salt hydrolase‑producing bacteria and bacterial hydroxysteroid dehydrogenase‑producing bacteria. These bile acids can affect host physiology by activating farnesoid X receptor Takeda G protein‑coupled receptor 5. Gut microbes can also induce MAFLD‑associated symptoms by producing tryptophan metabolites kynurenine, serotonin, and indole‑3‑propionate. A summary of bacterial genera involved in SCFAs production, bile acid transformation, and tryptophan metabolism is provided. Many bacteria have demonstrated efficacy in alleviating MAFLD in animal models and are potential therapeutic candidates for MAFLD. [ABSTRACT FROM AUTHOR]

Reconstructing the trajectory from the static image of handwritten ink traces is useful in many practical applications envisaging handwriting analysis and recognition from offline data, as it allows the use of methods, algorithms, and tools that deal with online data, achieving better results than those achieved on offline data. In this work, the trajectory recovery is addressed by combining a general graph traversal algorithm with knowledge about the processes involved in human learning of motor skills to perform voluntary and complex movements. The effectiveness of the proposed approach has been quantitatively and extensively evaluated on large and publicly available datasets, containing English and French multi-stroke words and isolated characters. The experimental results show that our approach outperforms the existing ones in terms of Root Mean Square Error and Dynamic Time Warping distance between the recovered trajectories and the actual ones. Furthermore, an "off-the-shelf" online recognition system provided with the trajectory recovered from offline samples showed an overall reduction of 6.8% with respect to the recognition rate achieved by the system when provided with online data; the reduction, however, drops to 2.4% once preprocessing errors are not taken into account. [ABSTRACT FROM AUTHOR]

While the nervous system may be best known as the sensory communication center of an organism, recent research has revealed a myriad of multifaceted roles for both the CNS and PNS from early development to adult regeneration and remodeling. These systems work to orchestrate tissue pattern formation during embryonic development and continue shaping pattering through transitional periods such as metamorphosis and growth. During periods of injury or wounding, the nervous system has also been shown to influence remodeling and wound healing. The neuronal mechanisms responsible for these events are largely conserved across species, suggesting this evidence may be important in understanding and resolving many human defects and diseases. By unraveling these diverse roles, this paper highlights the necessity of broadening our perspective on the nervous system beyond its conventional functions. A comprehensive understanding of the complex interactions and contributions of the nervous system throughout development and adulthood has the potential to revolutionize therapeutic strategies and open new avenues for regenerative medicine and tissue engineering. This review highlights an important role for the nervous system during the patterning and maintenance of complex tissues and provides a potential avenue for advancing biomedical applications. [ABSTRACT FROM AUTHOR]

Conventional drug discovery involves significant steps, time, and expenses; therefore, novel methods for drug discovery remain unmet, particularly for patients with intractable diseases. For this purpose, the drug repurposing method has been recently used to search for new therapeutic agents. Repurposed drugs are mostly previously approved drugs, which were carefully tested for their efficacy for other diseases and had their safety for the human body confirmed following careful pre-clinical trials, clinical trials, and post-marketing surveillance. Therefore, using these approved drugs for other diseases that cannot be treated using conventional therapeutic methods could save time and economic costs for testing their clinical applicability. In this review, we have summarized the methods for identifying repurposable drugs focusing on immunotherapy. [ABSTRACT FROM AUTHOR]

1,2-Dichloropropane (1,2-DCP) is recognized as the causative chemical of occupational cholangiocarcinoma in printing workers in Japan. However, the cellular and molecular mechanisms of 1,2-DCP-induced carcinogenesis remains elusive. The present study investigated cellular proliferation, DNA damage, apoptosis, and expression of antioxidant and proinflammatory genes in the liver of mice exposed daily to 1,2-DCP for 5 weeks, and the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in these responses. Wild-type and Nrf2-knockout (Nrf2 −/−) mice were administered 1,2-DCP by gastric gavage, and then the livers were collected for analysis. Immunohistochemistry for BrdU or Ki67 and TUNEL assay revealed that exposure to 1,2-DCP dose-dependently increased proliferative cholangiocytes, whereas decreased apoptotic cholangiocytes in wild-type mice but not in Nrf2 −/− mice. Western blot and quantitative real-time PCR showed that exposure to 1,2-DCP increased the levels of DNA double-strand break marker γ-H2AX and mRNA expression levels of NQO1, xCT, GSTM1, and G6PD in the livers of wild-type mice in a dose-dependent manner, but no such changes were noted in Nrf2 −/− mice. 1,2-DCP increased glutathione levels in the liver of both the wild-type and Nrf2 −/− mice, suggesting that an Nrf2-independent mechanism contributes to 1,2-DCP-induced increase in glutathione level. In conclusion, the study demonstrated that exposure to 1,2-DCP induced proliferation but reduced apoptosis in cholangiocytes, and induced double-strand DNA breaks and upregulation of antioxidant genes in the liver in an Nrf2-dependent manner. The study suggests a role of Nrf2 in 1,2-DCP-induced cell proliferation, antiapoptotic effect, and DNA damage, which are recognized as key characteristics of carcinogens. [ABSTRACT FROM AUTHOR]

Mass spectrometry is commonly used in forensic chemistry laboratories for sensitive, definitive analysis. There have been significant efforts to bring mass spectrometry analysis on-site through the development of ruggedized, fieldable instruments. Testing samples in the field is of particular interest in forensic science, homeland security, and defense applications. In forensic chemistry, testing seized drugs in the field can significantly improve efficiencies in processing of related criminal cases. The screening of passengers and luggage at transportation hubs is a critical need for homeland security for which mass spectrometry is well suited to provide definitive answers with low false positive rates. Mass spectrometry can yield reliable data for military personnel testing sites for potential chemical weapons release. To meet the needs of the forensic and security communities fieldable mass spectrometers based on membrane inlet systems and hybrid gas chromatography systems have been developed and commercialized. More recently developed ambient ionization mass spectrometry methods can eliminate the time, equipment, and expertise associated with sample preparation, and so are especially appealing for on-site analysis. We describe the development of fieldable mass spectrometry systems, with emphasis on commercially available systems that have been deployed for on-site analysis of seized drugs, chemical warfare agents, explosives, and other analytes of interest to the forensic and security communities. © 2020 John Wiley & Sons Ltd. Mass Spec Rev., (© 2020 John Wiley & Sons Ltd.)

Carbon dots (CDs), a class of carbon-based nanomaterials with dimensions less than 10 nm, have attracted significant interest since their discovery. They possess numerous excellent properties, such as tunability of photoluminescence, environmental friendliness, low cost, and multifunctional applications. Recently, a large number of reviews have emerged that provide overviews of their synthesis, properties, applications, and their composite functionalization. The application of CDs in the field of optoelectronics has also seen unprecedented development due to their excellent optical properties, but reviews of them in this field are relatively rare. With the idea of deepening and broadening the understanding of the applications of CDs in the field of optoelectronics, this review for the first time provides a detailed summary of their applications in the field of luminescent solar concentrators (LSCs), light-emitting diodes (LEDs), solar cells, and photodetectors. In addition, the definition, categories, and synthesis methods of CDs are briefly introduced. It is hoped that this review can bring scholars more and deeper understanding in the field of optoelectronic applications of CDs to further promote the practical applications of CDs., (© 2024 Wiley‐VCH GmbH.)

Background: Alcohol (ethanol) consumption has different influences on arterial disease, being protective or harmful depending on the amount and pattern of consumption. The mechanisms mediating these biphasic effects are unknown. Whereas endothelial cells play a critical role in maintaining arterial health, this study compared the effects of moderate and high alcohol concentrations on endothelial cell function. Methods: Human coronary artery endothelial cells (HCAEC) were treated with levels of ethanol associated with either low‐risk/moderate drinking (i.e., 25 mM) or high‐risk/heavy drinking (i.e., 50 mM) after which endothelial function was assessed. The effect of ethanol's primary metabolite acetaldehyde (10 and 25 μM) was also determined. Results: Moderate ethanol exposure (25 mM) improved HCAEC barrier integrity as determined by increased transendothelial electrical resistance (TEER), inhibited cell adhesion molecule (CAM) mRNA expression, decreased inflammatory cytokine (interferon‐γ and interleukin 6) production, inhibited monocyte chemotactic protein‐1 (MCP‐1) expression and monocyte adhesion, and increased homeostatic Notch signaling. In contrast, exposure to high‐level ethanol (50 mM) decreased TEER, increased CAM expression and inflammatory cytokine production, and stimulated MCP‐1 and monocyte adhesion, with no effect on Notch signaling. Reactive oxygen species (ROS) generation and endothelial nitric oxide synthase activity were increased by both alcohol treatments, and to a greater extent in the 50 mM ethanol group. Acetaldehyde‐elicited responses were generally the same as those of the high‐level ethanol group. Conclusions: Ethanol has biphasic effects on several endothelial functions such that a moderate level maintains the endothelium in a nonactivated state, whereas high‐level ethanol causes endothelial dysfunction, as does acetaldehyde. These data show the importance of dose when considering ethanol's effects on arterial endothelium, and could explain, in part, the J‐shaped relationship between alcohol concentration and atherosclerosis reported in some epidemiologic studies. [ABSTRACT FROM AUTHOR]

Chemical warfare agents (CWAs) are one of the most toxic compounds. Degradation of CWAs using decontamination agents is one of the few ways to protect human health against the harmful effects of CWAs. A ferrate (VI)-based potential chemical warfare agent decontaminant was studied for the degradation of persistent nitrogen mustard (tris(2-chloroethyl)amine, HN3). By optimizing the reaction conditions, the complete degradation of HN3 was achieved in 4 min. The degradation products contained mostly reduced Fe species, which confirmed the environmental friendliness of the proposed decontamination solution. [ABSTRACT FROM AUTHOR]

Nerve agents have been used recently in the Syrian civil war. Collecting relevant samples for retrospective identification of an attack is often problematic. The article deals with the possibility of using contaminated gloves as an analytical sample for evidence of the chemical weapons use. There have not yet been published studies dealing with the identification of chemical warfare agents in this type of matrix, where the diversity of chemical properties of gloves and the lifetime of the contaminated sample would be considered. Sarin, soman, and cyclosarin were used as contaminants in the study. Nitrile, latex, and vinyl disposable gloves were chosen as matrices. The identification method was gas chromatography. Six solvents commonly used in military laboratories were tested as extractants. The extraction procedure was optimized in terms of the appropriate method (vortex) and the required extraction time (1 min) and resulted in significant reduction in sample preparation time. The chromatographic background of the extracts was also monitored in order to find a method with the least number of peaks interfering in the identification. Suitable solvents were hexane and acetonitrile. The lifetime of the sample was also investigated. The worst result was recorded for latex. For individual contaminants, the time varied depending on the volatility. The developed procedures were successfully validated within a sample handling effects scenario. The results demonstrate that in the event of an ongoing military risk at the site of an attack, even discarded disposable rubber glove type samples can be used as evidence. [ABSTRACT FROM AUTHOR]

Amorphous metal oxide semiconductor phototransistors (MOTPs) integrated with colloidal quantum dots (QDs) (QD‐MOTPs) are promising infrared photodetectors owing to their high photoconductive gain, low off‐current level, and high compatibility with pixel circuits. However, to date, the poor mobility of conventional MOTPs, such as indium gallium zinc oxide (IGZO), and the toxicity of lead (Pb)‐based QDs, such as lead sulfide and lead selenide, has limited the commercial applications of QD‐MOTPs. Herein, an ultrasensitive QD‐MOTP fabricated by integrating a high‐mobility zinc oxynitride (ZnON)–based MOTP and lead‐free indium arsenide (InAs) QDs is demonstrated. A new gradated bandgap structure is introduced in the InAs QD layer that absorbs infrared light, which prevents carriers from moving backward and effectively reduces electron–hole recombination. Chemical, optical, and structural analyses confirm the movement of the photoexcited carriers in the graded band structure. The novel QD‐MOTP exhibits an outstanding performance with a responsivity of 1.15 × 105 A W−1 and detectivity of 5.32 × 1016 Jones at a light power density of 2 µW cm−2 under illumination at 905 nm. [ABSTRACT FROM AUTHOR]

Chirality induction is an important topic in studies of nanographenes (NGs). We report chirality enhancements of NGs through postsynthetic chemical modifications of NGs with pyrene and m‐terphenyl groups. These substituents were installed into N‐(p‐bromophenylethyl)imides on the edges of the NGs with Pd‐catalyzed cross‐coupling reactions. Circular dichroism (CD) spectra demonstrated that these bulky substituents improved the induced CD signal of the NGs compared to those previously reported and suggested that they induced the opposite chirality. Density functional theory calculations indicated possible edge structures for the NGs and indicated that π/π and CH/π interactions among the neighboring substituents influenced the orientations of the imides. These imides distorted the edges, and the distorted edges eventually generated the chiral environments of the NGs. The interactions among the substituents are, therefore, likely to allow detection of the CD signals in the visible region and induction of the opposite chirality. [ABSTRACT FROM AUTHOR]

Candida albicans is an opportunistic human fungal pathogen, and its drug resistance is becoming a serious problem. Camellia sinensis seed saponins showed inhibitory effects on resistant Candida albicans strains, but the active components and mechanisms are unclear. In this study, the effects and mechanisms of two Camellia sinensis seed saponin monomers, theasaponin E1 (TE1) and assamsaponin A (ASA), on a resistant Candida albicans strain (ATCC 10231) were explored. The minimum inhibitory concentration and minimum fungicidal concentration of TE1 and ASA were equivalent. The time–kill curves showed that the fungicidal efficiency of ASA was higher than that of TE1. TE1 and ASA significantly increased the cell membrane permeability and disrupted the cell membrane integrity of C. albicans cells, probably by interacting with membrane-bound sterols. Moreover, TE1 and ASA induced the accumulation of intracellular ROS and decreased the mitochondrial membrane potential. Transcriptome and qRT-PCR analyses revealed that the differentially expressed genes were concentrated in the cell wall, plasma membrane, glycolysis, and ergosterol synthesis pathways. In conclusion, the antifungal mechanisms of TE1 and ASA included the interference with the biosynthesis of ergosterol in fungal cell membranes, damage to the mitochondria, and the regulation of energy metabolism and lipid metabolism. Tea seed saponins have the potential to be novel anti-Candida albicans agents. [ABSTRACT FROM AUTHOR]