: Background: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcriptional factor nuclear factor κB (NFκB) is activated by cytokines, such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NFκB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NFκB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. Materials and Methods: Evaluation of safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSCh) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover. The efficacious concentration of Decoy determined from the rNSCh was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the level of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. Results: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 μM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life 63% and decreasing matrix metalloprotease 3 (MMP3) by 70.7% (P = 0.027). Conclusions: Decoy may be a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.

Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR–pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface plasmon resonance (SPR) methods quantify 3D affinity but lack cellular context and fail to account for factors like membrane fluctuations. In the recent years, single-molecule Förster resonance energy transfer (smFRET) has been applied to measure 2D binding kinetics of TCR–pMHC interactions in a cellular context. Here, we introduce a rigorous mathematical model based on survival analysis to determine exponentially distributed receptor–ligand interaction lifetimes, verified through simulated data. Additionally, we developed a comprehensive analysis pipeline to extract interaction lifetimes from raw microscopy images, demonstrating the model’s accuracy and robustness across multiple TCR–pMHC pairs. Our new software suite automates data processing to enhance throughput and reduce bias. This methodology provides a refined tool for investigating T cell activation mechanisms, offering insights into immune response modulation.

Pretreatment of cells with proteolysis inhibitors diminished intensity and changed shape of DNICs specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.

Continuous-wave photocathode guns are capable of delivering electron beams with high repetition rates and high average currents. However, they are limited by relatively low accelerating gradients and cathode fields. This limitation leads to a larger beam size at the gun exit due to space charge forces, making the beam more sensitive to optical aberrations and posing challenges for low-emittance electron beam transmission. This paper focuses on the aberrations induced by multipole fields. We analyze the effects of quadrupole, sextupole, and higher-order fields on beam profile and transverse emittance and propose a beam-based method for the rapid characterization and correction of these multipole fields. Furthermore, we present an experimental study conducted on the DC-SRF-II photocathode gun equipped with dedicated correctors. Both simulation and experimental results demonstrate that our approach effectively mitigates beam aberrations caused by multipole fields, resulting in improved beam symmetry and reduced emittance.

The rapid and accurate detection of viruses and the discovery of single nucleotide polymorphisms (SNPs) are crucial for disease management and understanding viral evolution. In this study, a pipeline for virus detection, validation, and SNP discovery from next-generation sequencing (NGS) data is presented. By integrating state-of-the-art bioinformatics tools with artificial intelligence, the pipeline processes raw sequencing data to identify viral sequences with high accuracy and sensitivity. Before aligning the reads to the reference genomes, quality control measures and adapter trimming are performed to ensure the integrity of the data. Unmapped reads are subjected to de novo assembly to reveal novel viral sequences and genetic elements. The effectiveness of the pipeline is demonstrated by the identification of virus sequences, illustrating its potential for the detection of known and emerging pathogens. SNP discovery is performed using a custom Python script that compares the entire population of sequenced viral reads to a reference genome. This approach provides a comprehensive overview of viral genetic diversity and identifies dominant variants and a spectrum of genetic variations. The robustness of the pipeline is confirmed by the recovery of complete viral sequences, which improves our understanding of viral genomics. This study highlights the synergy between traditional bioinformatics techniques and modern approaches, providing a robust tool for analyzing viral genomes and contributing to the broader field of viral genomics.

The progesterone receptor (PR) mediates progesterone regulation of female reproductive physiology, as well as gene transcription in non-reproductive tissues, such as brain, bone, lung and vasculature, in both women and men. An unusual property of progesterone is its high affinity for the mineralocorticoid receptor (MR), which regulates electrolyte transport in the kidney in humans and other terrestrial vertebrates. In humans, rats, alligators and frogs, progesterone antagonizes activation of the MR by aldosterone, the physiological mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark, ray-finned fishes and chickens, progesterone activates the MR. Interestingly, cartilaginous fishes and ray-finned fishes do not synthesize aldosterone, raising the question of which steroid(s) activate the MR in cartilaginous fishes and ray-finned fishes. The simpler synthesis of progesterone, compared to cortisol and other corticosteroids, makes progesterone a candidate physiological activator of the MR in elephant sharks and ray-finned fishes. Elephant shark and ray-finned fish MRs are expressed in diverse tissues, including heart, brain and lung, as well as, ovary and testis, two reproductive tissues that are targets for progesterone, which together suggests a multi-faceted physiological role for progesterone activation of the MR in elephant shark and ray-finned fish. The functional consequences of progesterone as an antagonist of some terrestrial vertebrate MRs and as an agonist of fish and chicken MRs are not fully understood. Indeed, little is known of physiological activities of progesterone via any vertebrate MR.

The presented work offers a novel process scheme for valorizing historical Pb-Zn slag, which involves crushing, grinding, and then using separation techniques to concentrate valuable components (nonferrous metals). This methodology could have a significant impact on the global beneficiation of metallurgical slags since, in theory, it is significantly more simple, environmentally friendly, and cost-effective than standard pyrometallurgical or hydrometallurgical procedures. According to previous physicochemical and mineralogical studies, Pb-Zn slag from "Topilnica" Veles is a valuable secondary raw material. This inhomogeneous technogenic resource contains substantial amounts of nonferrous metals (Pb, Zn, Cu, and Ag). However, laboratory tests have indicated that the Pb-Zn slag contains a very uneven valuable metals amounts, ranging from several g/ton to several tens of g/ton. The main issue is that traditional metallurgical procedures for releasing beneficial elements are not commercially viable since the valuable elements are "trapped" within amorphous aluminosilicates or intergrowths of alloy grains and glassy phases. Gravity concentration (Wilfley 13 shaking table) and magnetic separation (Davis separator and disk separator) were used to obtain the final concentrate following comminution and grindability testing. The gravity concentration proved more effective. This streamlined approach of valorizing Pb-Zn slag can reduce the need for hazardous chemicals used in hydrometallurgical refinement operations, as well as the extremely high temperatures required for pyrometallurgical processing. This is the first investigation into the feasibility of this novel approach, which includes direct investigations of the Pb-Zn slag feed using these alternative technologies. After extracting the valuable metals, the amorphous aluminosilicate part of the Pb-Zn slag can be reapplied as an alternative raw material in the building sector, adding to the circularity of the suggested approach..

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of >95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

This paper proposes a novel facial expression recognition network called the Lightweight Facial Network with Spatial Bias (LFNSB). The LFNSB model balances model complexity and recognition accuracy. It has two key components: a lightweight feature extraction network (LFN) and a Spatial Bias (SB) module for aggregating global information. The LFN introduces combined channel operations and depthwise convolution techniques, effectively reducing the number of parameters while enhancing feature representation capability. The Spatial Bias module enables the model to focus on local facial features while also capturing the dependencies between different facial regions. Additionally, a novel loss function called Cosine-Harmony Loss is designed. This function optimizes the relative positions of feature vectors in high-dimensional space, resulting in better feature separation and clustering. Experimental results on the AffectNet and RAF-DB datasets show that the proposed LFNSB model performs excellently in facial expression recognition tasks. It achieves high recognition accuracy while significantly reducing the number of parameters, thus substantially lowering model complexity.

This work (in two parts) will review the recently developed predictive modeling methodology called “4th-BERRU-PM” and its applicability to energy systems as exemplified by an illustrative application to the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark. The acronym 4th-BERRU-PM designates the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” methodology, which yields best-estimate results with reduced uncertainties for the first fourth-order moments (mean values, covariance, skewness, and kurtosis) of the optimally predicted posterior distribution of model results and calibrated model parameters. The 4th-BERRU-PM uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, including fourth (and higher) order sensitivities of computed model responses to model parameters, thus incorporating, as particular cases, the results previously predicted by the second-order predictive modeling methodology 2nd-BERRU-PM, and vastly generalizing the results produced by extant data assimilation and data adjustment procedures. The 4th-BERRU-PM methodology encompasses the scopes of high-order sensitivity analysis (SA), uncertainty quantification (UQ), data assimilation (DA) and model calibration (MC). The application of the 4th-BERRU-PM methodology to energy systems is illustrated by means of the above-mentioned OECD/NEA reactor physics benchmark, which is modeled using the neutron transport Boltzmann equation involving 21976 imprecisely known parameters, the solution of which is representative of “large-scale computations.” The model result (“response”) of interest is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. Part 1 of this work illustrates the impact of high-order sensitivities, in conjunction with parameter standard deviations of various magnitudes, on the determination of the expected value and variance of the computed response in terms of the first four moments of the distribution of the uncertain model parameters. Part 2 of this work will illustrate the capabilities of the 4th-BERRU-PM methodology for combining computational and experimental information, up to and including forth-order sensitivities and distributional moments, for producing best-estimate values for the predicted responses and model parameters while reducing their accompanying uncertainties.

The physical properties of a structure such stiffness although can be determined by some statical tests, the identification of damping parameter requires a dynamic test. In general, both theoretical prediction and experimental identification of damping are quite difficult. There are many different techniques available for damping identification, and each method gives a different damping parameter. The dynamic indentation method, rheometry, atomic force microscopy, and resonant vibration tests are commonly used to identify the damping of materials, including soft materials. While the viscous damping ratio, loss factor, complex modulus and viscosity are quite common to describe damping of materials, there are also other parameters such as the specific damping capacity, loss angle, half-power bandwidth, and logarithmic decrement to describe damping of various materials. Often one of these parameters is measured in practical applications and the measured damping parameter needs to be converted into another damping parameter for comparison purposes. In this review, the theoretical derivations of different parameters for the description and quantification of damping and their relationships, and the methods for damping identification are presented. The expressions for both high damping and low damping are included and evaluated. This paper could be a primary resource for damping research and teaching.

Background: Selectively targeting dopamine receptors has been a persistent challenge in the last years for the development of new treatments to combat the large variety of diseases evolving these receptors. Although, several drugs have been successfully brought to market, the subtype-specific binding mode on a molecular basis has not been fully elucidated. Methods: Homology modeling and molecular dynamics were applied to construct robust conformational models of all dopamine receptor subtypes (D1-like and D2-like receptors). Fifteen structurally diverse ligands were docked to these models. Contacts at the binding pocket were fully described in order to reveal new structural findings responsible for DR sub-type specificity. Results: We showed that the number of conformations for a receptor:ligand complex was associated to unspecific interactions > 2.5 Å and hydrophobic contacts, while the decoys binding energy was influenced by specific electrostatic interactions. Known residues such as 3.32Asp, the serine microdomain and the aromatic microdomain were found interacting in a variety of modes (HB, SB, π-stacking). Purposed TM2-TM3-TM7 microdomain was found to form a hydrophobic network involving Orthosteric Binding Pocket (OBP) and Secondary Binding Pocket (SBP). T-stacking interactions revealed as especially relevant for some large ligands such as apomorphine, risperidone or aripiprazole. Conclusions: This in silico approach was successful in showing known receptor-ligand interactions as well as in determining unique combinations of interactions, key for the design of more specific ligands.

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson´s Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the FDA, only a very small number is truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico / in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (KI = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of structural motifs responsible for DR subtype selectivity, thus, benefitting drug development in D2R/D3R-associated pathologies like PD.

The isotopic and nuclear techniques discussed, namely: Fallout Radionuclide, Fingerprint, and Isotope Hydrology, are linked to the evaluation of soil and water degradation processes. A traditional literature review was conducted to gain the most comprehensive understanding of both the current state of the art and the subject matter, with the aim of proposing a hypothesis that integrates the synergistic convergence of these techniques in order to offer results that are more reliable. A case study is presented as a synthesis of the preceding discussion.

Depressions containing partially molten rocks were investigated in Quaternary pebbly sedi-ments in Alpine foreland in Bavaria, Germany. Ruins of limekilns from 18-19th centuries are abundant around Seeshaupt. They are usually associated with earthworks for fuel feeding and protection from wind. Depressions contain partially molten stones from furnace walls, with lime and burnt loam remnants. On the surface of pebbles (typically gneisses), green glass formed with chemical composition possibly affected by moderately volatile components of wood biomass, mainly K and Cu. Thermoplastic deformation of pebbles is limited and the sur-face melt deformation points to slow flow. At Emmerting, on the other hand, two walled circu-lar depressions which lack additional earthworks have been identified as possible impact cra-ters. Thermally affected pebbles show much more intense deformation. Colorless to greenish glass, also K and Cu enriched, usually forms only thin surface coatings, in places covered by younger melt extruded from pebble interior. Burnt loam is missing. At Grabenstätt-Kaltenbach, a depression of unclear origin was investigated. Morphologically, it matches craters rather than limekilns, but anthropogenic contamination (brick-like material) is probable. The rare molten samples do not display extreme deformation features. The thermally affected stones, mainly those from Emmerting, have elevated magnetic susceptibility.

In this work, the surface of poly(ethylene terephthalate) track-etched membranes (PET TeMs) with pore sizes of 670-1310 nm was hydrophobized with 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptyl acrylate (DFHA) by photoinitiated graft polymerization. Attenuated total reflection FTIR spec-troscopy (ATR-FTIR), scanning electron microscopy (SEM) coupled to an energy-dispersive X-ray spectrometer (EDX), and contact angle measurement were used to identify and characterize the TeMs. The optimal parameters for graft polymerization were determined as follows: polymeriza-tion time 60 min, monomer concentration of 30% and distance from the UV-source 7 cm. The wa-ter contact angle of the modified membranes reached 97° which is 51o for pristine membranes. The modified membranes were tested for water desalination using direct contact membrane distillation (DCMD) method. The effect of membrane pore size, the degree of grafting and salt concentration on the performance of membrane distillation process was investigated. According to the results obtained, it has been concluded that large pore size hydrophobic TeMs modified by using DFHA could be used for desalinating water.

The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility and differentiation. Dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the “rotation model”). This model is also able to explain how oncogenic mutations activate the receptor in the absence of ligand without assuming that the mutations induce receptor dimerization. In this review, we discuss mechanisms underlying ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.

The optimization of ligand-receptor binding affinities is essential for enhancing therapeutic efficacy and specificity, particularly in the design of peptide-based drugs. ziconotide, a potent blocker of the N-type calcium channel CaV2.2, has demonstrated therapeutic potential in the treatment of moderate to severe chronic pain. However, there is limited structural and binding affinity data available for scaling the design of ziconotide analogues with improved efficacy and specificity. In this study, I present a structural biophysics-based approach to develop a scalable in silico framework for generating and analyzing ligand-receptor binding affinity landscapes, focusing on ziconotide and its receptor, CaV2.2. This framework integrates advanced computational structural tools and binding affinity calculations to produce high-accuracy structural and intermolecular binding data. The insights gained from this scalable approach will guide the design of ziconotide analogues with enhanced efficacy, offering a powerful computational workflow for high-throughput ligand optimization. Additionally, when combined with artificial intelligence (AI) algorithms, this computational workflow generates high-accuracy structural and biophysical data, towards an AI- and structural biophysics-driven paradigm shift in peptide discovery and design.

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. However, a theranostic radiopharmaceutical targeting the KISS1 receptor (KISS1R) has yet to be explored. A gallium-68 labelled kisspeptin-10 (KP10) has potential as a pan-tumor radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. We attached DOTA to the NH2-terminus of KP10 as we posited that this modification would not impair biological activity and showed that receptor stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene was similar for KP10 and DOTA-KP10. We describe optimization of radiolabeling with gallium-68 and lutetium-177 and stability in serum, plasma, and whole blood. Pharmacokinetics was established with µPET/CT and ex vivo measurements. Dynamic studies with µPET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 minutes. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These promising results advocate the further development of KP10 structures which have high binding affinity along with proteolytic resistance.

Background/Objectives: This study aimed to identify various risk factors associated with breast cancer and explore different treatment strategies based on socio-economic, hormonal, and clinical perspectives.; Methods: We analyzed socio-economic, hormonal, genetic, and clinical variables using data from 356 questionnaires obtained from breast cancer patients at Hassan II Regional Hospital in Agadir, Morocco ; Results:The study reveals that the average age of breast cancer patients is 50 ± 10.72 years, with a mode of 47 years and an age range from 29 to 94 years. Notably, women aged 38 are most frequently diagnosed with triple-negative breast cancer. Significant socio-economic trends were observed among the participants, with the majority being housewives (91%) and nearly half residing in rural areas (48.60%). High rates of illiteracy (74.72%) and financial difficulties (54.2%) pose challenges in accessing healthcare services. Psychological distress is prevalent, with 40.7% experiencing anxiety and 30.1% experiencing sadness. The use of oral contraceptives varies, with implications for breast cancer risk. Additionally, statistics on menarche and menopause suggest hormonal influences on breast cancer development. Histological analysis indicates a predominance of grade II invasive ductal carcinoma and left breast localization. Metastases are present in nearly 38.20% of cases. Notably, surgery as the primary treatment effectively treats medium-sized tumors while limiting metastasis. Furthermore, a comparison of treatment strategies reveals a preference for letrozole among postmenopausal patients and tamoxifen among premenopausal patients; Conclusions:These findings highlight the complexity of breast cancer risk factors and therapeutic approaches, emphasizing the importance of personalized care and targeted interventions.

In this paper, the neural network is developed for solving the inverse photoacoustic problem aiming to estimate thermo-elastic properties and thickness of a semiconductor sample. The idea was that these sample properties be estimated from the phase characteristic because the phase measurements are more sensitive. The neural network has been trained on a large basis of photoacoustic phases calculated from a theoretical Si n-type model in the range of 20Hz to 20kHz, on which random Gaussian noise has been applied. It is shown that high accuracy and precision could be reached in solving of inverse photoacoustic problem using only phase measurement.

This study investigates resource adequacy and renewable energy integration in the United States, European Union, and Pakistan amid global energy market liberalization and greenhouse gas re-duction efforts. It explores how these regions are adapting to the surge in renewable sources like wind and solar, which, despite their financial and environmental benefits, challenge resource adequacy and the economic viability of traditional energy sources. In the US and EU, significant improvements have been introduced in wholesale electricity markets and capacity accreditation mechanisms, which enhanced the large-scale deployment of renewables. This shift has prompted a reevaluation of resource adequacy, leading to increased deployment of battery storage and demand response. Presently, gas-based generation is largely upholding resource adequacy, however, future trends indicate a move towards greater consumer participation, energy efficiency, and utility-scale storage, with a decline in fossil fuel use. Pakistan aims to adopt a liberalized market structure by balancing competitive markets with legacy contracts. Public pressure is driving a shift from costly fossil-based generation to renewables. Similarly, a trend in the rise of behind-the-meter solar generation can be witnessed. In future, Pakistan may also experience resource adequacy challenges. It will likely need to implement battery storage, demand response, and modern capacity accreditation tools, by drawing lessons from developed markets.

Laser Photoacoustic Spectrometers (LPAS), which provide photoacoustic spectra for detecting food frauds or adulteration, and fluorescence-based systems for recognition of contamination by heavy metal ions in water are two important families of sensors for health and environmental purposes. Both sensor families require one or more low-frequency Lock-In Amplifiers (LIAs) to extract the signal of interest from background noise. In the cited applications, the required LIA frequency is quite low (up to 1kHz), and this leads to a simplification of the hardware with consequent good results in portability, economy, reduced size, weight and low-cost characteristics. The present system, called ENEA DSP Box Due, is based on a very inexpensive microcontroller proto-board and can replace four commercial LIAs, resulting in significant savings in both cost and space. Furthermore, it incorporates a dual-channel oscilloscope and a sinusoidal function generator. This article outlines the architecture of the ENEA DSP Box Due, its electrical characterization and its applications within a project concerning laser techniques for food and water safety.

There is evidence that chronic fatigue spectrum disorders (CFAS-D) including Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue with physiosomatic symptoms including when due to comorbid medical disease are characterized by neuroimmune and neuro-oxidative biomarkers. The present study was performed to delineate the protein-protein interaction (PPI) network of CFAS-D and to discover the pathways, molecular patterns and domains enriched in their PPI network. We performed network, enrichment and annotation analysis using differentially expressed proteins and metabolics, which we established in CFAS-D patients. PPI network analysis revealed that the backbone of the highly connective CFAS-D network comprises NFKB1, CTNNB1, ALB, peroxides, NOS2, TNF, and IL6, and that the network comprises interconnected immune-oxidative-nitrosative and Wnt/catenin subnetworks. MultiOmics enrichment analysis shows that the CFAS-D network is highly significantly associated with cellular (antioxidant) detoxification, hydrogen peroxide metabolic process, peroxidase and oxidoreductase activity, IL10 anti-inflammatory signaling, and neurodegenerative, canonical Wnt, the catenin complex, cadherin domains, cell-cell junctions and TLR2/4 pathways; and the transcription factors NF-κB and RELA. The top-10 DOID annotations of the CFAS-D network include four intestinal, three immune system disorders, cancer and infectious disease. Custom GO term annotation analysis revealed that the CFAS-D network is associated with a response to a toxic substance, lipopolysaccharides, bacterium or virus. In conclusion, CFAS-D may be triggered by a variety of stimuli and their effects are mediated by aberrations in the cross-talks between redox, NF-κB, and Wnt/catenin signaling pathways leading to dysfunctions in multicellular organismal homeostatic processes.

In this work SiC-Ti3AlC2 and TiC-Ti3AlC2 composites produced by additive manufacturing are investigated. The fused granules fabrication (FGF) method as one of the material extrusion additive manufacturing (MEAM) technology is used to obtain composite samples. Composites with different ratios between components and different powder:polymer ratios are investigated. The technological features of the additive formation of composites are investigated, as well as their structure and properties. The optimal sintering temperature to form the best mechanical properties for both composites is 1300 °C. The composites have a regulatable porosity. Ti3AlC2 content, sintering temperature, and polymer content in the feedstock are the main parameters that regulates the porosity of FGF samples.

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

The nuclear receptor superfamily comprises a large group of proteins with functions essential for cell signaling, survival and proliferation. There are multiple distinctions between nuclear superfamily classes defined by hallmark differences in function, ligand binding, tissue specificity, and DNA binding. In this review, we utilize the initial classification system, which defines subfamilies based on structure and functional difference. The defining feature of the nuclear receptor superfamily is that these proteins function as transcription factors. The loss of transcriptional regulation or gain of functioning of these receptors is a hallmark in numerous diseases. For example, in prostate cancer the androgen receptor is a primary target for current prostate cancer therapies. Targeted cancer therapies for nuclear hormone receptors have been more feasible than others to develop due to ligand availability and cell permeability of hormones. To better target these receptors, it is critical to understand their structural and functional regulation. Given that late-stage cancers often develop hormone insensitivity, we will explore the strengths and pitfalls of targeting other transcription factors outside of the nuclear receptor superfamily such as the signal transducer and activator of transcription (STAT).

SARS-CoV2 (corona virus) has spread globally at an unprecedented rate; so far, increasing SARS-CoV2-infected individuals have been identified. Although the situation in China is improving and is currently under control, the outbreak in other countries and its pandemic management is only beginning to develop. Based on 154 SARS-CoV2 genome sequence analyses, we used receptor–ligand docking to identify one potential point mutation (V354F) on the spike structure which enhances spike binding to ACE2 receptors underlying potential super infection. Importantly, the V354F site on spike S1 had been identified in 5/10 infected French patients living in Paris, who sharing 100% identical SARS-CoV2 genomes. With Covid-19 cases increasing rapidly in France that could lead to a new explosion, we suggest that the French government should identify all potential super spreaders and treat them accordingly. In summary, our study provides on of the measures to avoid the potential second worldwide explosion of SARS-CoV2.

Substances that can modify the androgen receptor pathway in humans and animals are entering the environment and food chain with the proven ability to disrupt hormonal systems and leading to toxicity and adverse effects on reproduction, brain development, and prostate cancer, among others. State-of-the-art databases with experimental data of human, chimp, and rat effects by chemicals have been used to build machine learning classifiers and regressors and evaluate these on independent sets. Different featurizations, algorithms, and protein structures lead to dif- ferent results, with deep neural networks (DNNs) on user-defined physicochemically-relevant features developed for this work outperforming graph convolutional, random forest, and large featurizations. The results show that these user-provided structure-, ligand-, and statistically-based features and specific DNNs provided the best results as determined by AUC (0.87), MCC (0.47), and other metrics and by their interpretability and chemical meaning of the descriptors/features. In addition, the same features in the DNN method performed better than in a multivariate logistic model: validation MCC = 0.468 and training MCC = 0.868 for the present work compared to evalu- ation set MCC = 0.2036 and training set MCC = 0.5364 for the multivariate logistic regression on the full, unbalanced set. Techniques of this type may improve AR and toxicity description and predic- tion, improving assessment and design of compounds. Source code and data are available at https://github.com/AlfonsoTGarcia-Sosa/ML

In this paper, the time-resolved model of photoacoustic signal for samples with a complex inner structure is derived including local non-equilibrium of structural elements with multiple degrees of freedom, i.e. structural entropy of the system. The local non-equilibrium is taken into account through the fractional operator. By analyzing the model for two types of time-dependent excitation, a very short pulse and a very long pulse, it is shown that the rates of non-equilibrium relaxations in complex samples can be measured by applying the derived model and time-domain measurements. Limitations of the model and further directions of its development are discussed.

Multilayered metallic sheets fabricated by hot metal forming processes are attractive structural components in the aerospace and automobile industry. The strength of the mechanical bond between the different layers is critical to the applicability of such components in load bearing applications. While it is well understood that the process conditions such as temperature, deformation and rate of deformation influence the bond strength, a clear functional relationship between these conditions and the bond strength has yet to be established. The objective of the current study is to investigate the joining of Aluminum-6061 alloy specimens by hot compression bonding. Hot compression tests of beam specimen pairs were conducted at different temperatures (300-500℃), with different strains and strain rates (10-2-10-1 [1sec]). Coupled thermo-mechanical finite element models were utilized to compute the time dependent thermo-mechanical fields that develop along the specimen interface. The computed values were used to map the spatial distribution of a scalar parameter J which is hypothesized to govern bond formation. Mechanical tensile tests were used to determine the bond strength and expose the bonded surfaces. It is demonstrated that the computed J distribution can be correlated well with SEM observations of the debonded surface. It is also shown that the actual bonded area can be predicted from the computations for a certain range of critical J values.

Background/Objectives: Although the role of F-18 FDG PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, we retrospectively studied 134 CRC patients referred for FDG PET/CT imaging on the suspicion of recurrence based on elevated CEA and/or CA 19-9, and/or equivocal radiological findings. According to the Institutional Tumor Board CRC protocol, after initial treatment which was dependent on TNM stage (neoadjuvant therapy, primary resection or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy every 6 months. The statistics including univariate and multivariable analyses were conducted using the IBM SPSS 20.0 statistical software. P-values <0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. FDG PET/CT shows high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA shows a high sensitivity of 98.1%, but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy, for CA 19-9 and CIM for the correct diagnosis in CRC patients were: 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for FDG PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p<0.001), 0.844 (95% CI: 0.772-0.916; p<0.001), 0.753 (95% CI: 0.612-0.844; p<0.001); and 0.547 (95% CI: 0.442-0.652; p=0.358). Univariate analysis shows that both FDG PET/CT- and CIM-positive results were highly associated with CRC recurrence (p<0.001 and p<0.001, respectively), while gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) have no significance (p=0.211, p=0.158, p=0.583, and p=0.201, respectively). Our multivariate analysis shows that independent predictors for CRC recurrence are: positive FDG PET/CT scans (p<0.001), positive CIM results (p=0.001) and elevated CA19-9 levels (p=0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p=0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting CRC recurrence (p=0.023). Conclusions: FDG PET/CT shows a high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the postoperative follow-op in patients with elevated tumor markers.

The paper describes an application of machine learning approach for parameter optimization. The method is demonstrated for the elasto-viscoplastic model with both isotropic and kinematic hardening. It is shown that the proposed method based on long-short term memory networks enabled to obtain reasonable agreement of stress-strain curves for cyclic deformation in low-cycle fatigue regime. The main advantage of the proposed approach over traditional optimization schemes lies in the possibility to get parameters for a new material without the necessity to conduct any further optimizations. As the power and robustness of the developed method was demonstrated on the very challenging problem (cyclic deformation, crystal plasticity, self-consistent model, isotropic and kinematic hardening), it is directly applicable to other experiments and models.

The Atmospheric Dynamics Mission ADM-Aeolus was successfully launched in August 2018 by the European Space Agency (ESA). The Aeolus mission carried a single instrument, the first-ever Doppler Wind Lidar (DWL) in space, called Atmospheric LAser Doppler INstrument (ALADIN). Aeolus circled the Earth in a polar sun-synchronous orbit at about 320 km altitude with a repeat cycle of 7 days, providing vertical profiles of horizontal line-of-sight (HLOS) winds on a global scale. Exceeding scientific expectations, Aeolus, initially designed for a 3-year lifetime, provided global coverage of wind profiles for almost five years. In this long-term validation study, we assessed the accuracy of the Level 2B (L2B) Rayleigh-clear and Mie-cloudy wind products by collecting radiosonde data from three stations in the Brazilian Amazon: Cruzeiro do Sul (7.62° S, 72.67° W), Porto Velho (8.76° S, 63.91° W), and Rio Branco (10.00° S, 67.80° W). Statistical validation was conducted by comparing Aeolus L2B wind products and radiosonde data, launched daily at 12:00 UTC from October 2018 to March 2023. Considering all data collected during the mission period, Pearson’s coefficient (R) of 0.73 was observed in Rayleigh-clear and 0.85 in Mie-cloudy, revealing a strong correlation between Aeolus and radiosonde winds. No significant biases were detected, with values of -0.14 m/s for Rayleigh-clear and -0.40 m/s for Mie-cloud, fulfilling the mission requirement of having absolute biases below 0.7 m/s. However, when analyzed annually, in 2022, the bias for Rayleigh-clear was -0.95 m/s, exceeding the mission requirements.

Background: Ventilator-associated pneumonia (VAP) is among the most common healthcare-associated infections in Pediatric Intensive Care Units (PICUs). Because of the lack of a gold-standard diagnostic test, early diagnosis of VAP is challenging. We investigated whether bronchial biomarkers interleukin-4 (IL-4), plasminogen activator inhibitor-1 (PAI-1) and soluble receptor for advanced glycation end products (RAGE) could contribute in early VAP diagnosis through their fluctuation in time in critically ill pediatric patients. Methods: Bronchial secretions were collected from PICU patients with VAP on days 1 and 6. PAI-1, RAGE and IL-4 levels were measured by ELISA. Protein concentrations between high and low VAP suspicion patients were compared using unpaired Student’s t or Mann–Whitney U tests. Results: Twenty PICU patients, with median age 7.75yrs (range 0.5-15.3), mechanically ventilated for ≥48hrs with increased oxygenation requirements and VAP clinical/laboratory signs were enrolled. They were divided in VAP high-suspicion (n=12) or low-suspicion (n=8) groups based on Clinical Pulmonary Infection Score (cutoff:6). ΡΑΙ-1 και RAGE levels did not differ between high- or low-VAP suspicion groups the 1st or 6th days (p-value&gt;0.05). IL-4 was not detected in bronchial secretions. Conclusion: Bronchial concentrations of IL-4, PAI-1 and RAGE in critically ill children are not correlated with high- or low-VAP suspicion.

Investigation of functional magnetic resonance imaging (fMRI) data with machine learning (ML) techniques, including also deep learning (DL) methods, have been widely used to study Autism Spectrum Disorder (ASD). This disorder is characterized by symptoms that affect the individual’s behavioral aspects and social relationships. Early diagnosis is crucial for intervention, but the complexity of ASD poses challenges for treatment development. This study compares traditional ML techniques with deep learning (DL) methods in the analysis of functional connectivity measures obtained from the time series of multicentric ABIDE dataset. Specifically, Support Vector Machines (SVM) classifiers, with both linear and Radial Basis Function (RBF) kernels, as well as eXtreme Gradient Boosting (XGBoost) classifiers, are compared against the TabNet classifier, which is a DL architecture customized for tabular data analysis and a Multi Layer Perceptron (MLP). The findings suggest that DL classifiers may not be optimal for the type of data analyzed, as their performance trails behind that of standard classifiers. SVMs achieve performances, in terms of AUC, around 75%, compared to the best TabNet and MLP results, which are 65% and 71%, respectively. Additionally, this work investigates the brain regions that contribute most to the classification task, which are found to be those primarily responsible for sensory and spatial perception, as well as attention modulation, known to be altered in ASD.

The importance of personalized medicine is growing, since there is an urged need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for a specific molecular targeting in means of diagnostics and therapy. The visualisation of potential targets can help to predict if a patient would benefit from a particular treatment or not. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents is constantly rising. In this article important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with the well-known radioiodine therapy in patients with thyroid cancer and then guides through different approaches for the treatment of advanced cancer with targeted therapies. The aim of this review is to provide a summary of background knowledge, current applications and advantages of targeted therapies and imaging in nuclear medicine practice.

Abstract: Imaging of low (LGG) to high (HGG) grade gliomas is conventionally performed with MRI, which is the non-invasive gold-standard imaging modality to derive data. Gliomas (Grade 1,2,3,4) are lethal and demonstate poor outcomes despite novel therapies. Integrins compose of heterodimeric parasympathetic nervous system; the aVb3 (RGD i.e. Galacto-Arginine-Glycine-Aspartic acid) have been displayed as a potential biomarker that can be imaged via PET in order to trace the angiogenetic pathway. Gliomas are common primary central nervous system (CNS) tumours which are often pose a diagnostic challenge, even to stage and manage because of their heterogeneity in molecular aberrations. Several core mutational core hallmarks of gliomas are inducing/accessing vasculature, tumour promoting inflamation, polymorphic microbes and avoiding/resisting cell death; these ultimately lead to poor prognosis. In 2007, the classification of diffuse gliomas was based on the histopathology and subtype e.g. Pilocytic astrocytoma and low cell proliferation, in 2016, the classification of diffuse gliomas was based on the IDH status, 1p/19q codeletion, subtype and grade; then in 2021, the IDH status (wild-type or mutant), molecular profile, subtype and grade were added in order to improve the classification of diffuse gliomas. Imaging (MRI) techniques progress stalled despite the imperfections in MRI e.g distinguishing RN (radionecrosis) and PsP (Pseudoprogression) hence the exploration of PET probes that detect important hallmarks of gliomas e.g. techniques such as [68Ga]68Ga-RGD positron emission tomography (PET) to be utilised to assess vasculature. This case report aimed to determine the potential clinical utility of molecular imaging with 68Ga-RGD PET used in complementary to traditional MRI techniques.

Plant activators have emerged as promising alternatives to conventional pesticides for crop disease manage-ment due to their unique mode of action. By priming the plant's innate immune system, these compounds can induce systemic acquired resistance against a broad spectrum of pathogens without directly inhibiting their proliferation. Key advantages of plant activators include prolonged defense activity, lower effective dosages, and negligible risk of developing pathogen resistance. Among the various defensive pathways tar-geted, the salicylic acid (SA) signaling cascade has been extensively explored, leading to the successful devel-opment of commercial activators like benzothiadiazole for widespread application in crop protection. While the action sites of many SA-targeting activators have been preliminarily mapped to different steps along the pathway, a comprehensive understanding of their precise mechanisms remains elusive. This review provides a historical perspective on plant activator development and outlines diverse screening strategies employed across multiple levels, from whole-plant bioassays to molecular and transgenic approaches. We expound on the intricate components, biological relevance, and regulatory circuits governing the SA pathway, while criti-cally examining the structural features, bioactivities, and proposed modes of action of classical activators such as benzothiadiazole derivatives, salicylic acid analogs, and other small molecules. Insights from field trials as-sessing their practical applicability are also discussed. Furthermore, we highlight the current status, challenges, and future prospects in the realm of SA-targeting activator development globally, with a focus on recent en-deavors in China. Collectively, this comprehensive review aims to synthesize existing knowledge and provide a roadmap for future research toward developing more potent and mechanistically understood plant activa-tors that fortify crop immunity against disease.

Bulk composition, mineralogy and microchemistry of various fractions of the filling of the Crater No. 4 at Emmerting were investigated. Here we present mainly the fine fractions, which, in contrast to pebbles larger than ca. 4 cm, are relatively poor in material affected by melting. A 0.1 mm long meteorite fragment without ablation features was found, and remelted fragments of the same body have been identified. The projectile was dominated by enstatite, also containing forsterite, basic plagioclase, Ni-rich pyrrhotite and troilite, kamacite, silica, and probably merrillite. The molten fragments contain porous Mg-rich glass (indicating temperature &gt; 1500 °C), minor Fe oxides, and occasionally uncommon Ni-rich minerals. The bulk composition and electron microprobe show that the amount of meteoritic material is low (&lt;&lt; 1 %), and it is not unequivocally manifested even in platinum-group elements abundances and osmium isotope ratios (the latter, however, were only measured in two samples). This can be explained by dilution of the filling by particles brought after the crater formation, and by probably achondritic composition of the projectile. Relatively large hollow spheroid Fe oxide particles were observed in thin sections from the magnetic fraction. A Mn oxide hollow spherule has also been found. In magnetically separated filling from the nearby Crater No. 5, bulk chemical composition points to contamination with several metals and metalloids probably due to influence of recent alluvial sediments. Therefore, the extent of meteoritic contamination in this crater may be even smaller.

The true ternary fission, the fission of a nucleus into three fragments of nearly equal mass, is an elusive and poorly known process influenced by shell effects. It has been envisaged an increase of the probability of this process with respect to the binary fission, very low in spontaneous and neutron-induced fission, by adopting heavy-ion induced reactions due to the possibility to increase the fissility parameter and the excitation energy of the compound nuclei. Nuclei with mass number around A=250, accessible in heavy-ion induced reactions, are favorable and should be investigated. It is still debated if the process takes place in a single step, direct ternary fission, or in two steps, sequential ternary fission. The purpose of this work is to define experimental conditions and observables that allow the disentangling of the products from the direct and sequential ternary fission as well as from the usual most probable binary fission. This step is essential to gain insight on the ternary fission dynamics and on the binary to ternary fission competition. The method proposed here is to simulate the kinematics of the ternary and binary fission processes to compute the energy distributions and angular correlations of direct and sequential ternary fission products, as well as those of binary fission. The reaction taken as benchmark is 40Ar+208Pb at 230 MeV supposed to form the 248Fm* compound nucleus. The simulation results have been filtered by considering the response function of a multi-coincidence detection system virtually constructed using the Geant4 simulation toolkit. The simulations support the possibility to separate the products of different multimodal fission decays with the proposed setup that consequently represents an effective tool to get insight on ternary fission from the observables selected.

Pancreatic cancer is a refractory cancer with limited treatment options. Various cancer types are resistant to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Eugenol, the main component of clove oil, exhibits anticancer, anti-inflammatory, and antioxidant effects. However, no studies have reported that eugenol increases TRAIL sensitivity by upregulating death receptor (DR) expression. Here, we aimed to investigate eugenol as a potent TRAIL sensitizer. Increased apoptosis and inhibition of cell proliferation was observed in pancreatic cancer cells treated with eugenol and TRAIL compared with those treated with eugenol alone. Eugenol upregulated the expression of DR5, inhibited FLICE-inhibitory protein (FLIP), an anti-apoptotic protein, and increased p53, a tumor suppressor protein. In addition, eugenol induced the generation of reactive oxygen species (ROS) and caused endoplasmic reticulum (ER) stress. C/EBP-homologous protein (CHOP) knockdown using siRNA decreased the expression of DR5 and reduced the combined effects of eugenol and TRAIL. These results demonstrate that eugenol enhances TRAIL-induced apoptosis by upregulating DR5 through the ROS-mediated ER stress-CHOP pathway, enhancing ER stress by inducing p53 and downregulating FLIP expression. This suggests that eugenol has the potential to treat pancreatic cancer by increasing cell sensitivity to TRAIL.

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p&lt;0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

Background: Since cytokine receptor like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno associated virus (AAV) or AAV containing CRLF1 was determined by morpholog-ical, histological and microCT analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were deter-mined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes us-ing real time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondro-genic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and Cardiotrophin like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Taking into account modern technologies in the mining industry and in the processing of industrial waste, we propose to reprocess cemented low- and intermediate level radioactive waste by extracting all chemical compounds from them. Because of the low cost of space flights in the near future, we propose to use chemical compounds, extracted from radioactive waste, in the production of space electronics and structural materials for automatic space probes and rovers. At the same time, since nano- and micro powders, as well as composites with these fillers, are widely used today in electronics and technology, including in the space industry, the production of radioactive powders and composites will provide new scientific results in the field of materials science and solid-state physics, since nothing is known today about the properties of radioactive powders and composites containing radioactive sources inside.

This study introduces numerical advancements in an alternative design for the SPS Beam Dump Facility (BDF) at CERN. The design envisions a high-power operation target made of flowing liquid lead. The BDF is a proposed versatile facility at CERN, intended for both beam-dump-like and fixed-target experiments. The target behavior is assessed, assuming a proton beam with a momentum of 400 GeV/c, a pulse frequency of 1/7.2 Hz, and an average beam power of 355 kW. An evaluation is conducted using various Computational Fluid Dynamics (CFD) codes to analyze the behavior of liquid lead and to predict the thermal stress on the target vessel induced by the pulsed heat source generated by the charged particle beam. The comparison increases the reliability of the results, investigating the dependencies on the CFD modeling approach. The beam is modeled as a volumetric heat source with data coming from beam-lead interaction simulations provided by CERN and obtained with the Monte-Carlo code FLUKA. The velocity field and stress profiles are utilized to enhance the design of the lead loop and verify its viability and safety when operated with a liquid metal target.

The nuclear reactor measurement system is a crucial component of the nuclear measurement system in a nuclear power plant. Its primary function is to measure the power distribution within the reactor core using detectors, calibrate, and provide data on core fuel consumption. Therefore, the study of the detectors' reliability is crucial for ensuring the safe operation of the nuclear power system. The article describes the operational mechanism of the gas ionization chamber detector utilized in the intermediate-range detector of the off-board nuclear measurement system. It also analyzes the movement of particles between the plates during the ionization process of the nuclear reaction taking place in the detector. The functional relationship between the current in the recombination region and the ionization region involved in the actual working condition, and the change with the increase of voltage between the plates, is deduced. A mathematical model is established for the number of pulses generated between the plates and the magnitude of the voltage between the plates. Subsequently, the change in the offset of the voltage corresponding to the inflection point of the ping curve and the change rule of the slope of the ping curve are investigated. Combined with the analysis of experimental data, the results show that the initial particle energy of Ar+, the primary sensitive particle on the detector surface, follows a normal distribution and is influenced by the energy loss associated with the initial velocity and the voltage between the plates. The trends of the inflection points and slopes of the ping curves can be utilized to evaluate the performance and operational status of the detector. Combined with the results of the experimental data analysis, the fit is good, and the inflection point currents in the normal state decrease by about 1.5% annually. The intelligent diagnostic system, based on the method studied in this paper, has been successfully implemented in the RPN digital retrofit and upgrade project at Qinshan No. 2 Plant.

Compared to agonists, radiolabeled somatostatin receptor (SSTR) antagonists have advantages in neuroendocrine tumors (NETs). Articles on radiolabeled somatostatin receptor agonists or antagonists in NETs were included by searching the Web of Science (WoS) database. The included literature has been subjected to data collection and bibliometric study. A detailed analysis of the included clinical articles was also performed. 123 publications were identified for biblio-metric analysis. The number of publications on radiolabeled somatostatin receptor agonists and antagonists in the theranostics of NETs has increased significantly after 2014, with Germany publishing the most papers (39), followed by the United States (33) and Switzerland (28). The Swiss paper was cited the most, with 1783 quotations, followed by the USA (1338) and Germany (1330). The most common keywords were NETs (89), Peptide receptor-mediated radionuclide therapy (PRRT) (62), and antagonists (53). Antagonists had lower uptake in normal tissue and higher uptake in tumor tissue compared to agonists, with a high tumor-to-liver ratio. Research on radiolabeled somatostatin receptor agonists and antagonists in theranostics of NETs is increasing, with significant contributions from Europe and the United States. Radiolabeled somatostatin receptor antagonists are likely to be a hot topic in NETs theranostics.

This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate syn-thase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in se-rum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment sig-nificantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, en-hanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This ap-proach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.

LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and its binding activity to the EGFR antigen were evaluated. Furthermore, the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the significant accumulation and sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.

(1) Background: To investigate the effect of phosphohistone H3 (PHH3) and vitamin D receptor (VDR) in the risk assessment of endometriosis, in two cohorts of women with this pathology, those receiving hormonal treatment, and those without treatment; (2) Methods: In 60 cases of women with endometriosis, the paraffin-embedded endometriosis tissue samples, retrieved after surgery, were immunohistochemically (IHC) analyzed aiming to determine the expression status of PHH3 and VDR; (3) Results: The IHC positive index of PHH3 and VDR of these two groups were compared. PHH3 levels were positively correlated with vitamin D levels, both being increased in patients without treatment. Within the group without treatment, PHH3 and VDR expressions were positively associated; (4) Conclusions: IHC analysis of PHH3 and VDR can be used as an additional tool for risk stratification and prognostic assessment in patients with endometriosis.

Non-woven jute (NWJ) produced from the carpet industry waste was oxidized by H2O2 or alkali treated by NaOH and compared with water-washed samples. Changes in the structure of the NWJ, tracked by XRD, showing that both chemical treatments disrupt hydrogen bond networks between cellulose Iβ chains of the NWЈ fibers. Thereafter, nano carbon nitride (nCN) was impregnated, using layer-by-layer technique, onto water washed jute sample (nCN-Jw), NaOH treated sample (nCN-Ja) and H2O2 treated sample (nCN-Jo). Analysis of the FTIR spectra of the impregnated samples, revealed that nCN anchors to the water washed NWЈ surface through hemicellulose and secondary hydroxyl groups of the cellulose. In the case of chemically treated samples nCN is preferentially bonded to the hydroxymethyl groups of cellulose. The stability and reusability of nCN-J samples were assessed by tracking the photocatalytic degradation of Acid Orange 7 (AO7) dye under simulated solar light irradiation. Results from up to ten consecutive photocatalytic cycles demonstrated varying degrees of effectiveness across different samples. nCN-Jo and nCN-Ja samples exhibited declining effectiveness over cycles, attributed to bond instability between CN and jute. In contrast, the nCN-Jw sample consistently maintained high degradation rates over ten cycles, with a dye removal percentage constantly above 90%.

Gliomas are common primary central nervous system (CNS) tumours which are often very difficult to diagnose, stage and manage because of their heterogeneity and molecular aberrations. The notable hallmark of gliomas is integrated genome mutations and methylome that correlates with distinctive patterns of transcription that potentiates glioma heterogeneity, angiogenesis and ultimately poor prognosis. The World Health Organization (WHO) has decided to reclassify gliomas based on molecular markers rather than the traditional anatomical basis; use of Nuclear Medicine techniques e.g. SPECT/PET and Magnetic Resonance Imaging (MRI) techniques based on molecular markers is set to become the future gold standards. This has led to the investigations on potential for the use of non-invasive imaging techniques such as [68Ga]68Ga-RGD positron emission tomography (PET) to be utilised routinely in clinical practice based on angiogenic markers and also the potential to add information that may assist in drug-design and therapeutic decision making. This review aims to provide an overview of the basis of recent advances in glioma imaging using molecular targeting with positron emission tomography and SPECT imaging, as well as the role in patient management i.e. diagnosis, staging, recurrence detection etc.

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a ``natural selection'' of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the ``thermodynamic dissipation theory for the origin of life'' argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic ``design goals'' of microscopic dissipative structuring of organic UV-C pigments, today known as the ``fundamental molecules of life'', from common precursors under this light. This ``UV-C Pigment World'' evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons, up to wavelengths of the ``red-edge''. The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.

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.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

The German health authorities' guidelines for medical devices in 2012 highlighted the importance of cleaning ultrasound probes, emphasizing their validation and reliability. In addition to automated and validated options, alternative manual methods such as wipe disinfection have gained traction due to their independence from additional hardware. The study examines the effectiveness of manual disinfection methods, specifically the cleaning process, addressing concerns raised by the Robert Koch Institute regarding the lack of validation for wipe disinfection of semi-critical devices. The EQUINOS colored wipe disinfection kit identified wetting gaps in all cleanings across four probes tested. The results indicate significant challenges in ensuring complete surface wetting, particularly in complex body parts such as clip-on areas and shapes for additional biopsy attachments, suggesting that manual methods alone may not adequately mitigate the risk of infection transmission (p value .001). The study concludes that while manual disinfection methods are a viable alternative to automated reprocessing, there is a critical need for enhanced training and potentially the development of more effective manual disinfection techniques or colored wipes to ensure patient safety and compliance with healthcare hygiene standards.

(1) Background: Many malignancies are driven by mutations which affect the gene for fibroblast growth factor receptor (FGFR) 1. Previously we have documented that signal transduction from FOP2–FGFR1 fusion protein in KG1 cells downregulated the expression of vitamin D receptor (VDR) gene. In this paper we investigated if also other FGFRs were responsible for the regulation of the VDR expression. (2) Methods: We used human myeloid leukemia cells U937, and bone cancer cell line U2OS, and cell transfection methods in order to address the above questions. (3) Results: In myeloid leukemia cells overexpression of FGFR 1-4 caused shift to granulocytic differentiation, upregulated expression of VDR, and sensitized these cells to 1,25-dihydroxyvitamin D (1,25D)-induced monocytic differentiation, while in bone cells, signal transduction activated by FGF1 was not responsible for regulation of VDR expression and activity. (4) Conclusions: Since the overexpression of FGFRs occurs in many neoplasms, it may be reasonable to use 1,25D analogs in these cancers, in which overexpression of FGFRs leads to VDR upregulation.

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that involve in regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result downstream activation of tyrosine kinases leading to tumor development. Targeting those FGFR alterations has shown to be effective in cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments of multiple agents targeting FGFR pathway including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody drug conjugates. However, most of these agents have variable and low responses with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments of agents targeting FGFR pathway and discuss future directions of FGFR targeting agents.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

A tritium resistant coating on the surface of materials is one of the main methods to reduce tritium permeability. In actual operating processes, mechanical damage such as spalling and scratches will occur on the surface of tritium resistant coatings. These mechanical damages will affect the hydrogen permeability resistance of the coatings. It is an important engineering problem that evaluate the effect of these damage on the tritium resistance of the coating. In this experiment, the mechanical damage of FeAl/Al2O3 tritium resistant coating on 316L stainless steel was simulated by scratching, debonding and thermal shock, and the gas hydrogen isotope permeation (GDP) test was carried out. The influence of mechanical damage degree on the tritium permeation behaviour of the coating was evaluated and discussed.

The increasingly common occurrence of antibiotic-resistant bacteria has become an urgent public health issue. There are currently some infections without any effective treatment, which require new therapeutic strategies. An attractive alternative is the design of compounds capable of disrupting bacterial communication known as quorum sensing (QS). In gram-negative bacteria, such communication is regulated by acyl-homoserine lactones (AHLs). QS allows bacteria to proliferate before expressing virulence factors. Our group previously reported that hexyloxy phenyl imidazoline (9) demonstrated 71% inhibitory activity of QS at 100 µM (IC50=90.9 µM) in Chomobacterium violaceum, a gram-negative bacterium. The aim of the present study was to take 9 as a lead compound to design and synthesize three 2-imidazolines (13-15) and three 2-oxazolines (16-18), to be evaluated as quorum sensing inhibitors on C. violaceum CV026. We were looking for compounds with a higher affinity towards the Cvi receptor of this bacterium and the ability to inhibit QS. The binding mode of the test compounds on the Cvi receptor was explored with docking studies and molecular dynamics. It was found that 8-pentyloxyphenyl-2-imidazoline 13 reduced the production of violacein (IC50=56.38 µM) without affecting bacterial growth, suggesting inhibition of quorum sensing. Indeed, compound 13 is apparently one of the best QS inhibitors known to date. Molecular docking revealed the affinity of compound 13 for the orthosteric site of the N-hexanoyl homoserine lactone (C₆-AHL) on the CviR protein. Ten aminoacid residues in the active site of C₆-AHL interacted with 13, and 7 of these are the same as those interacting with AHL. Contrarily, 8-octyloxyphenyl-2-imidazoline 14, 8-decyloxyphenyl-2-imidazoline 15 and 9-decyloxyphenyl-2-oxazoline 18 bound only to an allosteric site and thus did not compete with C₆-AHL for the orthosteric site.

The Shimensi super-large tungsten polymetallic deposit is located in Late Jurassic- Early Cretaceous Porphyry-Skarn tungsten ore belt in the south Yangtze metallogenic belt. There are 3 types of mineralization: veinlet-disseminated type, thick quartze vein type and hydrothermal crypto-explosive breccia type. Based on geological studies, this paper presents new petrographic, microthermometric, laser Raman spectroscopic and hydrogen and oxygen isotope research of the fluid inclusions from the deposit. The results show that there are five different types of fluid inclusions: liquid-rich inclusions, vapor-rich inclusions, pure liquid inclusions, pure vapor inclusions, and fluid inclusions containing a solid crystal. The homogenization temperatures of the fluid inclusion range from 140℃-270℃, the salinities are 3%-5% NaCleq and the densities of ore-forming fluid range from 0.64 g/cm3 to 0.99 g/cm3. For the analyses of Laser Raman spectroscopic, the ore-forming fluids can be approximated by a Ca2+-Na+-SO42--Cl- fluid system with small amount of CO2, CH4 and N2. Otherwise, the datas of the pressure, pH and Eh show a fluid metallogenic environment of low pressure, weak acid and weak reduction. The values of the homogenization temperature in 3 types of orebodies suggest that the mineralization is characterized by the decrease of the temperature under the condition of the fluid immiscibility. The H-O isotope values are interpreted to indicate that the ore-forming fluids are mainly composed of magmatic water, and also the meteoric water was added with the process of the magma rising.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

We have repeated the experiment performed recently by Krasznahorkay et al., (Phys. Rev. Lett. 116, 042501 (2016)), which may indicate a new particle called X17 in the literature. In order to get a reliable, and independent result, we used a different type of electron-positron pair spectrometer which have a more simple acceptance/efficiency as a function of the correlation angle, but the other conditions of the experiment were very similar to the published ones. We could confirm the presence of the anomaly measured at the Ex=18.15 MeV resonance, and also confirm their absence at the Ex=17.6 MeV resonance, and at Ep= 800 keV off resonance energies.

Nuclear waste is one of the most important environmental problems of nuclear power plants. A novel renewable distillation method has been proposed for an on-site recycling of the spent nuclear fuel and separation of its valuable components from the fissile isotopes, which is especially applicable for reactors using liquid fuels.

The direct detection of dark matter constituents, in particular the weakly interacting massive particles (WIMPs), is central to particle physics and cosmology. In this paper we develop the formalism for WIMP-Nucleus induced transitions from isomeric nuclear states. We specialize it in the case of the experimentally interesting target 180 Ta

Paper presents proposition of possible extension of The Standard Model Classification of Particles and Fields in way to include gravitation into it.

In the last three decades the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because of their role in signalling acting. Here we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling both in physiological and pathological conditions.

This review paper focuses on the joint toxicity and interaction of carbon-based nanomaterials (CNMs) with co-existing pollutants in aquatic environments. It explores the potential harmful effects of chemical mixtures on living organisms, emphasizing the importance of scientific mod-eling to predict mixed toxic effects. The study involved a systematic literature review to gather information on the joint toxicity and interaction between CNMs and various co-contaminants in aquatic settings. A total of 53 publications were chosen and analyzed, categorizing the studies based on the tested CNMs, types of co-contaminants, and the used species. Common test models included fish and microalgae, with zebrafish being the most studied species. The review under-scores the necessity of conducting mixture toxicity testing to assess whether the combined effects of CNMs and co-existing pollutants are additive, synergistic, or antagonistic. The development of in silico models based on the solid foundation of research data represents the best opportunity for joint toxicity prediction, eliminating the need in a great quantity of experimental studies.

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., pro-NGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. Besides pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

We prove that it is necessary to introduce the non-zero gluon masses into the fundamental Lagrangian of Quantum Chromodynamics in order to describe the mass-gap in the reaction of electron-positron annihilation into hadrons. A new restriction on the gluon masses is obtained. The renormalized theory with non-zero Lagrangian gluon masses is constructed.

Aedes albopictus is considered one of the major invasive species in the world and can transmit viruses such as dengue, Zika, or chikungunya. The Sterile Insect Technique (SIT) can be used to suppress the native populations of Ae. albopictus. To support the development of the release strategy during the SIT application, Mark-Release-Recapture (MRR) studies are crucial. Mean-while, weather conditions can affect the MRR trial’s results and it is critical to understand the influence of climatic factors on the results. In October 2022 in Faro, Southern Portugal, 84,000 ir-radiated sterile males were released for three consecutive weeks and mosquitoes were recapture by Human Landing Collections (HLC) one, two, four and six days after. Generalised linear models with a negative binomial family and log function were used to estimate the factors asso-ciated with the number of recaptured mosquitoes, prevalence ratios, and the 95% confidence in-tervals (CI). A total of 84,000 sterile male mosquitoes were released, with 528 recaptured (0.8%) by HLC. The prevalence of recaptured mosquitoes was 23% lower when the wind intensity was moderate. Sterile-marked males had an average median distance travelled of 88.7 m. Median probability of daily survival and the average life expectancy were 61.6% and 2.1, respectively. Wild male population estimates was 443.33 males/ ha. Despite no statistically significant asso-ciation was found with humidity, temperature and precipitation, it is crucial to consider weather conditions during MRR trials analyses to obtain the best determinants estimation and a more ef-ficient application of SIT in an integrated vector management program.

Electricity load forecasting is a crucial undertaking within all the deregulated markets globally. In contemporary times, the transition from conventional electricity grids to Smart Grids constitutes an area where extensive research is conducted on a global scale. Among the research challenges, the investigation of Deep Transfer Learning (DTL) in the field of electricity load forecasting represents a fundamental effort that imparts generality to Artificial Intelligence applications, due to new capabilities, such as knowledge transfer and computational power reduction. In this paper a comprehensive study is conducted for day-ahead electricity load forecasting. For this purpose, three Sequence-to-Sequence (Seq2seq) Deep Learning (DL) models are used, namely the Multilayer Perceptron (MLP), the Convolutional Neural Network (CNN) and the Ensemble Learning Model (ELM), which is consisted of the weighted combination of the outputs of MLP and CNN models. Also, the study focuses on the development of different forecasting strategies based on DTL and emphasizing the way the datasets are trained and fine-tuning for higher forecasting accuracy. In order to implement the forecasting strategies using Deep Learning models, load datasets from three Greek islands, Rhodes, Lesvos, and Chios, are used. The main purpose is to apply DTL for day-ahead predictions (1-24 hours) for each month of the year for Chios dataset after training and fine-tuning the models using the datasets of the three islands in various combinations. After several trials, four DTL strategies are illustrated. In the first strategy (DTL Case 1), each of the three DL models is trained using only Lesvos dataset, while fine-tuning is performed on the dataset of Chios island, in order to create day-ahead predictions for Chios load. In the second strategy (DTL Case 2), data from both Lesvos and Rhodes concurrently are used for the DL model training period, and fine-tuning is performed on the data from Chios. The third DTL strategy (DTL Case 3) contains the training of the DL models using Lesvos dataset, and the testing period performed directly on the Chios dataset without fine-tuning. The fourth strategy is a Multi-task Deep Learning (MTDL) approach, which has been extensively studied in recent years. In MTDL, the three DL models are trained simultaneously on all three datasets and the final predictions are made on the unknown part of the dataset of Chios. In this paper, we explore the performance of DTL and compare the results with those produced with MTDL. The results demonstrated that DTL can be applied with high efficiency for day-ahead load forecasting. Specifically, the two cases with fine-tuning (DTL Case 1 and 2) outperformed MTDL in terms of load prediction accuracy. Regarding the DL models, all three exhibit very high prediction accuracy, especially in the two cases with fine-tuning. The ELM excels compared to the single models. More specifically, for conducting day-ahead predictions, it has been concluded that the MLP model presents best monthly forecasts with a MAPE of 6.24% and 6.01% for the first two cases, the CNN model presents best monthly forecasts with a MAPE of 5.57% and 5.60% respectively and the ELM model achieves best monthly forecasts with a MAPE of 5.29% and 5.31%, respectively, indicating the very high accuracy it can achieve.

Human epidermal growth factor receptor 2 (HER2) belongs to the ErbB family, a group of four transmembrane glycoproteins with tyrosine kinase activity, all structurally related to the epidermal growth factor receptor (EGFR). These tyrosine kinases are involved in the transmission of cellular signals controlling normal cell growth and differentiation. If this transmission goes awry, it can lead to dysregulated growth of the cell. HER2 specifically can be implicated in the pathogenesis of at least eight malignancies. HER2 positivity quickly became a well characterized indicator of aggressiveness and poor prognosis, with high rates of disease progression and mortality. After realizing the implication of HER2, it first became investigated as a target for treatment in breast cancer, and later expanded to areas of research in other cancers types. To this day, the most therapeutic advancements of anti-HER2 therapy have been in breast cancer, however, there have been strong advancements made in the incorporation of anti HER2 therapy in other cancer types as well. This comprehensive review dissects HER2 to its core incorporating the most up to date information. The topics touched upon are discussed in detail and up to 200 published sources from the most highly recognized journals have been integrated. The importance of knowing about HER2 is exemplified by the groundbreaking advancements that have been made, and the change in treatment plans it has brought to the oncological world in the last twenty years. Since, its ground breaking discovery there has been significant breakthroughs in knowledge regarding the actual receptor, the receptors biology, its mechanism of action, advancements in tests to detect HER2 and significant strides on how to best incorporate targeted treatment. Due to the success of this field thus far, the review concludes by discussing the future of novel anti-HER2 therapy currently in development that everyone should be aware of.

Outliers seriously affect the accuracy in geometric model fitting. Previous works in coping with outliers involve threshold selection and scale estimation. However most scale estimators suppose the inlier distribution as a Gaussian model, which usually poorly meets the cases in geometric model fitting. Outliers, considered as the points with big residuals to all the true models, share common items with big values in quantized residual preferences, thus making the outliers gather away from the inliers in quantized residual preference space. In this paper we make use of this outlier consensus in quantized residual preference space by extending the usage of energy minimization to combine the model error and the spatial smoothness in quantized residual preference space for outlier detection. The energy minimization based outlier detection process follows an alternate sampling and labeling framework. After the outlier detection, an ordinary energy minimization method is employed to optimize the inlier labels, which also follows the framework of alternate sampling and labeling. The experimental results in this study show that the energy minimization based outlier detection method can detect most of the outliers in the data. Furthermore, the proposed energy minimization based inlier segmentation process segments the inliers into different models quite accurately. Overall, the performance of the proposed method is better than most of the state-of-the-art methods.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is an important target of monoclonal antibody (mAb) therapy such as trastuzumab. Due to the development of trastuzumab-deruxtecan, an antibody-drug conjugate, the targetable HER2-positive breast cancer patients have been expanded. To evaluate developing modalities using anti-HER2 mAbs, reliable preclinical mouse models are required. Therefore, sensitive mAbs against mouse HER2 (mHER2) should be established. This study developed mHER2 mAbs using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mHER2 mAbs, H2Mab-300 (rat IgG2b, kappa) and H2Mab-304 (rat IgG1, kappa), reacted with mHER2-overexpressed Chinese hamster ovary-K1 (CHO/mHER2) and endogenously mHER2-expressed cell line, NMuMG (a mouse mammary gland epithelial cell) by flow cytometry. Furthermore, these mAbs never recognized mHER2-knockout NMuMG cells. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) of H2Mab-300 and H2Mab-304 for CHO/mHER2 was 1.2 × 10−9 M and 1.7 × 10−9 M, respectively. The KD of H2Mab-300 and H2Mab-304 for NMuMG was 4.9 × 10−10 M and 9.0 × 10−10 M, respectively. These results indicated that H2Mab-300 and H2Mab-304 could apply to the detection of mHER2 using flow cytometry and may be useful to obtain the proof of concept in preclinical studies.

The microstructure evolution during the cold rolling and subsequent annealing of Alloy 800H was investigated. Two distinct rolling methods, unidirectional rolling and cross-rolling, were intro-duced. Results show that better ductility was observed in the unidirectional rolling than in cross-rolling, whilst a higher volume fraction of large deformed grains was observed in the cross-rolled plates than in the unidirectionally rolled plates. Recrystallization occurred faster in plates from unidirectional rolling than from cross-rolling.

In this work, we studied light-output properties, efficiency function as well as PSD capability of p-Terphenyl scintillator. The selected solid cylindrical scintillation detector has a size of (45 x 45) mm with PSD properties. Recently presented studies of light-output functions have been meas-ured only for low neutron energies. Our motivation has been to determine more accurate the light output function for p-Terphenyl scintillator over a wider neutron energy range. The measurements have been carried out with mono-energetic neutron beams in the wide energy range from 2.5 to 19 MeV. The neutron-gamma spectrometric system, which we developed has been used for the measurement. The input analogue signal from the detector is digitized with fast 12-bits analogue to digital converter with sampling frequency of 1 GHz. Measured data from the detector are processed into gamma and neutron spectra. The light output function for protons has been determined by finding the position of the protons for given neutron energies. The more accurate light output function for p-Therphenyl scintillator has been calculated. The pulse-shape discrimination capability as well as efficiency of p-Terphenyl scintillator in comparison with NE-213 equivalent detector is lower.

The Epidermal Growth Factor Receptor (EGFR) overexpression or its mutation mediates the sustaining proliferative signaling in cancers. Human EGFR-targeting monoclonal antibody (mAb) therapy such as cetuximab has been approved for clinical use in patients with colorectal cancers and head and neck squamous cell carcinomas. A reliable preclinical mouse model is essential to further develop the mAb therapy against EGFR. However, a mAb against mouse EGFR (mEGFR) for flow cytometry has not been established. In this study, we developed a specific and sensitive mAb for mEGFR using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mEGFR mAb, EMab-300 (rat IgG1, kappa) reacted with mEGFR-overexpressed Chinese hamster ovary-K1 (CHO/mEGFR) and endogenously mEGFR-expressed cell lines, including NMuMG (a mouse mammary gland epithelial cell) and Lewis lung carcinoma cells by flow cytometry. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) of EMab-300 for CHO/mEGFR and NMuMG was 4.3 × 10−8 M and 1.9 × 10−8 M, respectively. These results indicated that EMab-300 applies to the detection of mEGFR by flow cytometry, and is expected in the use of preclinical study.

Hepatitis B virus (HBV) infection is a major factor in development of various liver diseases such as hepatocellular carcinoma (HCC). Among HBV encoded proteins, HBV X protein (HBx) is known to play key role in development of HCC. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear transcription factor which is critical for hepatocyte differentiation. However, the expression level as well as its regulatory mechanism in HBV infection have yet to be clarified. Here, we observed the suppression of HNF4α in cells which stably express HBV whole genome or HBx protein alone, while transient transfection of HBV replicon or HBx plasmid had no effect on the HNF4α level. Importantly, in the stable HBV- or HBx-expressing hepatocytes, the downregulated level of HNF4α was restored by inhibiting ERK signaling pathway. Our data showed that HNF4α was suppressed during long-term HBV infection in cultured HepG2-NTCP cells as well as in mouse model following hydrodynamic injection of pAAV-HBV or in mice intravenously infected with rAAV-HBV. Importantly, HNF4α downregulation increased cell proliferation which contributed to the formation and development of tumor in xenograft nude mice. The data presented here provided several proofs for the effect of HBV infection in manipulating HNF4α regulatory pathway in HCC development.

Any material object vibrating or rotating excites in spacetime around gravitational waves. Atomic nucleus being highly dynamical object also excites continuously micro gravitational waves which might form around the nucleus specific structure resembling optical diffraction grating and which gives huge effect to nuclear elastic scattering cross sections. The close similarity between the nuclear diffractive scattering and the optical Debye-Sears Effect is shown.

Simple summary This reassessment of the findings from our Phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate-high risk prostate cancer in the absence of androgen-deprivation therapy due to patient’s refusal, with a median follow-up of 6.5 years. Our primary focus is on analysing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade 2 or higher, both genitourinary and gastrointestinal. Abstract Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intraprostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intraprostatic recurrences occurred in 7 patients (21%), with ≥ 75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patient. Notably, 5 patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intraprostatic recurrences. Extended follow-up revealed grade 2 or higher late GU and GI toxicity in 18% (n=6) and 6% (n=2) of the patients. Conclusions: Among patients with intermediate-high risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: focal dose escalated prostate SBRT prevented recurrences in the dominant nodule, however extra-prostatic recurrence sites were frequent.

Aim: Sca-1+CD31− cells were shown to be endothelial stem/progenitor cells, found in many mammalian tissues, including heart, were able to differentiate into cardiomyocytes in vitro and in vivo. Our previous work indicated that heart derived Sca-1+CD31− cells increased Nr1d1 mRNA level and decreased cells plasticity with aging. However, little is known about how NR1D1 affects Sca-1+CD31− cells plasticity. Methods: Lentiviral vector was used to stably overexpress Nr1d1 in young Sca-1+CD31− cells and to knockdown Nr1d1 in aged Sca-1+CD31− cells. Cell differentiation, proliferation, apoptosis, and cell cycle were evaluated. Results and Conclusions: The overexpression of Nr1d1 in young Sca-1+CD31− cells inhibited cell proliferation and promoted apoptosis. Knockdown of Nr1d1 in aged Sca-1+CD31− cells promoted cell proliferation and inhib-ited apoptosis. Using mouse cardiac myocytes cell line, confirmed the effect of Nr1d1 and indi-cated that Nr1d1 induce Serpina3 expression via Nr1d1 interaction with Nr4a3. Nr1d1 may there-fore be identified as a potent anti-aging receptor and be a therapeutic target for aging relative diseases.

A dioxomolybdenum catalyst [(MoO2Cl2-O-MoO2Cl2)(L)] (1) (with L (1S,2S)-N,N´-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex showed to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, occurring the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) showed to be influenced by the presence of water in the system. Using 50% aq. H2O2 it was possible to reuse the catalyst and the extraction solvent MeOH during ten consecutive cycles without loss of desulfurization efficiency.

The promoter of the RECEPTOR-LIKE CYTOPLASMIC KINASE VI_A2 gene contains nine binding sites for the REPLUMLESS transcription factor. In agreement, the expression of the kinase gene was strongly downregulated in the rpl-4 mutant. Comparing phenotypes of loss-of-function mutants, it was revealed that both genes are involved in stem growth, phyllotaxis, organization of the vascular tissues, and the replum, highlighting potential functional interactions. Expression of the RLCKVI_A2 gene from the constitutive 35S promoter could not complement the rpl-4 phenotypes, but exhibited a dominant positive effect on stem growth and affected vascular differentiation and organization. The results also indicated that the number of vascular bundles is independently regulated from stem thickness. Although our study cannot demonstrate the direct link between the RPL and RLVKVI_A2 genes, it highlights the significance of the proper developmental regulation of the RLCKVI_A2 promoter for balanced stem development.

Microglial cells are highly specialized central nervous system (CNS) cells that can promote the inflammation and neurodegeneration seen in Multiple Sclerosis (MS). MS is a neurodegenerative autoimmune disease characterized by inflammation, demyelination, and axonal degeneration. In MS patients, demyelination is associated with activated microglia. Endothelin-1 (ET-1) is a potent vasoconstrictor that induces severe and prolonged cerebral vasoconstriction and inflammation. However, the mechanism of how ET-1 activates a proinflammatory response in the CNS is unknown. To investigate ET-1’s role in microglia activation, HMC3 cells were treated with ET-1 in the presence or absence of endothelin receptor B antagonist, BQ788. TNFα and IL-6 levels were measured using ELISA. Nitric Oxide (NO) production was measured using Griess Reagent. Reactive oxygen species (ROS) production was measured using the MUSE Oxidative Stress kit. ET-1 increases TNFα levels by 56% (p= 0.0003) and IL-6 levels by 86% (p= 0.0111) in HMC3 cells, and it was decreased to basal levels in the presence of BQ788. NO and ROS production is induced by ET-1 (p&lt;0.05), and treatment with BQ788 was able to decrease them. ET-1 increases STAT-1 activation by 3.5 folds compared to control (p &lt;0.0001) in microglia cells. Moreover, to study ET-1 levels in MS, we used C57BL/6 mice brains with or without induced experimental autoimmune encephalomyelitis (EAE). The brain ET-1 levels were measured by qPCR and ELISA. We found that the ET-1 gene and protein were upregulated by 1.5 folds (p= 0.0199) in EAE mice compared to the control. These data suggest that in vitro administration of ET-1-activated microglia significantly increased inflammatory cytokine levels and NO and ROS formation. This novel mechanism of microglial cell activation will provide key information to understand MS pathogenesis.

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia. AZ683 has high affinity for CSF1R (K_i = 8 nM; IC₅₀ = 6 nM) and >250-fold selectivity over 95 other kinases and, in this paper, we report the radiosynthesis of [¹¹C]AZ683 and initial evaluation of its use in CSF1R PET. [¹¹C]AZ683 was synthesized by ¹¹C-methylation of the desmethyl precursor with [¹¹C]MeOTf in 3.0% non-corrected activity yield (based upon [¹¹C]MeOTf), >99% radiochemical purity and high specific activity. Preliminary PET imaging with [¹¹C]AZ683 revealed no brain uptake in rodents and nonhuman primates suggesting that [¹¹C]AZ683 is a poor candidate for imaging neuroinflammation, but that it could still be useful for peripheral imaging of inflammation.

Purpose: We aimed to develop a nomogram able to predict treatment failure, skeletal events and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). Patients and Methods: Patients from Castilla-La Mancha Spanish region was prospectively included in ChoPET-Rad multicenter study, from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using Kaplan-Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. Results: Median progression-free survival (PFS) and OS for our population were 4 and 14 months (mo), respectively. The variables that showed the most robust independent significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p=0.022) and the characteristics of BM on CT portion of PET/CT (p=0.017). In the case of OS, the significant variables were therapeutic failure (p=0.038), the number of lines received after 223Ra (p

The Ultra-Cold Neutron (UCN) source being commissioned at North Carolina State Universityâs PULSTAR reactor is uniquely optimized for UCN production in the former graphite-filled thermal column outside of the reactor pool. The source utilizes a remote moderation design which is particularly well suited to the PULSTAR reactor on account of its large thermal and epithermal neutron leakage from the core face. This large non-equilibrium flux from the core is efficiently transported to the UCN source through the specially designed beam port in order to optimize UCN production at any given reactor power. The increased distance to the source from the core also greatly limits the heat load on the cryogenic system. A MCNP model of this system was developed and is in good agreement with gold foil activation measurements using a mock-up setup as well as with the real UCN source heavy water moderator. These results established a firm baseline for estimates of the cold neutron flux available for UCN production and prove that remote moderation in a thermal column port is a valuable option for future designs of cryogenic UCN sources.

To support the integration of renewable energy sources and preserve grid stability, this study examines several approaches for controlling the temperature of Battery Energy Storage Systems (BESS) in modern energy settings. Specifically, the usage of BESS in Virtual Power Plants (VPPs) is the focus of this study. The effectiveness, safety features, dependability, affordability, and suitability for VPP applications of these systems are examined. Among the various hybrid cooling alternatives, two particularly promising combinations emerge. Firstly, the integration of heat pipes and phase change materials leverages their ability to conduct heat efficiently away from heat sources with minimal temperature differences, making them excellent for rapid heat transfer. Secondly, an approach employing heat pipes and liquid passive cooling a combination that capitalizes on the efficient heat transfer capabilities of heat pipes and the consistent cooling offered by liquid passive systems. The study underscores the importance of improving BESS performance and sustainability within VPPs by providing useful recommendations for choosing the best thermal management system depending on climate conditions and geographic location.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

PARP inhibitors are used in tumor therapy exploiting their inhibitory role in DNA repair. Radiation therapy leads to DNA damage in the affected region comprising both tumor tissue and adjacent normal tissue. In addition, radiotherapy has long-standing effects on DNA integrity. The mechanisms for this are not well understood. We studied normal tissue damage of the lung after application of ionizing radiation (IR) in two well established rat models comprising both external (eIR) and internal (iIR) ionizing radiation. We found a nearly complete (~350-fold) loss of PARP-1 in the irradiated tissue in both models but no change in PARylated protein. This may be explained by the strong decrease in both ARH3 and PARG, both deparylating enzymes. We demonstrate, that of all these proteins are expressed in type II pneumocytes, but also in type I pneumocytes and the bronchiolar epithelium. The data suggest a severe disturbance of PARylation in these cells which may affect their major functions such as maintenance of the integrity of the alveolar wall. It is likely that the application of PARP inhibitors could have cumulative effects in radiation-damaged normal tissue.

Glycogen storage disease type III (GSDIII) is a hereditary glycogenosis caused by deficiency of the glycogen debranching enzyme (GDE), an enzyme, encoded by Agl, enabling glycogen degradation by catalyzing alpha-1,4-oligosaccharide side chain transfer and alpha-1,6-glucose cleavage. GDE deficiency causes accumulation of phosphorylase-limited dextrin, leading to liver disorder followed by fatal myopathy. We tested here the capacity of the new autophagosomal activator GHF-201 to alleviate disease burden by clearing pathogenic glycogen surcharge in the GSDIII mouse model Agl-/-. We used open field, grip strength and rotarod tests for evaluating GHF-201’s effects on locomotion, biochemistry panel to quantify hematological biomarkers, indirect calorimetry to quantify in vivo metabolism, transmission electron microscopy to quantify glycogen in muscle, and fibroblast image analysis to determine cellular features affected by GHF-201. GHF-201 was able to improve all locomotion parameters and partially reversed hypoglycemia, hyperlipidemia and liver and muscle malfunction in Agl-/- mice. Treated mice burnt carbohydrates more efficiently and showed significant improvement of aberrant ultrastructural muscle features. In GSDIII patient fibroblasts, GHF-201 restored mitochondrial membrane polarization and corrected lysosomal swelling. In conclusion, GHF-201 is a viable candidate for treating GSDIII as it recovered a wide range of its pathologies in vivo, in vitro, and ex vivo.

This paper presents the fabrication and characterization of cylindrical capacitors utilizing magnetodielectric materials composed of magnetizable microfibers dispersed within a silicone oil matrix. The microfibers, ranging in diameter from 0.25 to 2.20 μm, comprise hematite (α-Fe2O3), maghemite (γ-Fe2O3), and magnetite (Fe3O4). The study investigates the electrical behavior of these capacitors under the influence of an external magnetic field superimposed on a medium-frequency alternating electric field, across four distinct volume concentrations of microfibers. Electrical capacitance and resistance measurements are conducted every second over a 60-second interval, revealing significant dependencies on both the quantity of magnetizable phase and the applied magnetic flux density. Furthermore, the temporal stability of the capacitors’ characteristics is demonstrated. The obtained data are analyzed to determine the electrical conductance and susceptance of the capacitors, elucidating their sensitivity to variations in microfiber concentration and magnetic field strength. To provide theoretical insight into the observed phenomena, a model based on dipolar approximations is proposed. This model effectively explains the underlying physical mechanisms governing the electrical properties of the capacitors. These findings offer valuable insights into the design and optimization of magnetodielectric-based capacitors for diverse applications in microelectronics and sensor technologies.

Oxytetracycline (OTC) serves as a widely employed antibiotic in veterinary treatment and prevention of infections, potentially leaving residues in animal-derived food products, such as milk, that are consumed by humans. Given the detrimental effects of prolonged human exposure, it becomes imperative to develop precise and sensitive methods for monitoring the presence of OTC in food. This work reports on the fabrication of a label-free electrochemical aptasensor for the determination of OTC as a proof-of-concept.

With reference to Planck scale Hubble parameter, super luminal expansion speeds, super luminal rotation speeds, Mach’s principle and Holographic principle, we review the current cosmological observations with eight simple assumptions. By understanding Yuri N. Obukhov and V.A. Korotky proposed cosmic rotational effects of polarization of radiation due to massive bodies, to some extent cosmic rotation can be deep-rooted in an observational approach and the ratio of current angular velocity and Hubble parameter can be estimated. It is possible to show that, at H₀ =70 km/sec/Mpc, current cosmic temperature, age, radius, mass, mass density are 2.721 K, 4.41x10¹⁷ sec, 90 billion light years, 1.14654x10⁵⁴ kg, 0.0482 times the current critical density respectively. Clearly speaking, current universe seems to constitute 267 Hubble spheres. Important point to be noted is that, current rotational kinetic energy is 0.6667 times the current critical energy. Based on the estimated current mass density and current rotational kinetic energy, current cosmic dark matter density can be shown to be 0.2851 times the current critical density. These numerical coincidences cast serious doubt on the on the real existence of currently believed ‘dark energy’. Initial and current expansion speeds are 3x10⁸ m/sec and 3.56x10⁹ m/sec respectively. With increasing cosmic age and increasing cosmic expansion speed, current universe is expanding with a speed of 11.885c. By knowing the time to time future cosmic temperatures, future Hubble parameters and corresponding future cosmic expansion speeds can be estimated and thus future expansion speed can be understood. Starting from ‘speed of light’, our model assumes a continuous increase in expansion speed and attains a current radius of 90 billion light years (without inflationary concepts) and casts a serious doubt on the actuality of currently believed ‘inflation’.

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

Background/Objectives: Vascular invasion, especially extramural vascular invasion (EMVI) has emerged as prognostic parameter for rectal cancer (RC) in recent years. Prediction of reccurence and metastases development poses a significant challenge for oncologists, needing markers for prediction of adverse outcome. The aim of this study was to examine the prognostic significance of pathohistologically detected EMVI in untreated rectal cancer and its implications in separate reporting. Methods: We examined 100 untreated RC patients who underwent curative resection from January 2016 to June 2018 with follow up of 5 years. Patients were divided in equal EMVI- and EMVI+ groups based on histological re-examination of H&E stained postoperative surgical samples. Results: The presence of EMVI within the selected cohort was significantly associated with female gender, T3/T4 and N1/N2 post-operative stages, positive lymph nodes, lymph node ratio LNR2 and LNR3 groups, abundant tumor-infiltrating lymphocytes, positive lympho-vascular invasion (LVI), perineural (PNI), and circumferential resection margin (CRM) (p<0.05 in all tests). Within EMVI+ patients, local recurrences and/or metastases, and death outcomes were more frequent events (p=0.029 and p=0.035, respectively), while survival analyses revealed that EMVI+ patients had significantly shorter overall survival (OS, p=0.040) and disease-free survival (DFS, p=0.028). Concerning LVI, differences in OS between LVI+ and LVI- patients were not statistically significant (p=0.068), while LVI+ patients had significantly shorter DFS (p=0.024). Moreover, univariate COX regression analysis demonstrated the negative impact of EMVI on OS (HR: 2.053, 95% CI: 1.015-4.152; p=0.045) and DFS (HR: 2.106, 95% CI: 1.066-4.870; p=0.038), which was not the case for LVI+ RC patients. Conclusions: Obtained results strongly suggest significance of separate reporting of EMVI from lympho-vascular invasion, as it is potentially a surogate marker for adverse prognosis and outcome.

Solanum nigrum fruits have been conventionally available as a material of beverage due to its nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols and anthocyanins. Here has rarely reported on the characterizaton of the components and the regulatory mechanism of Anthocyanins in S. nigrum. In this study, we determined that the peel and flesh of S. nigrum fruits shared the similar HPLC profiles, but the different contents and total antioxidant activities for Anthocyanins. After an efficient purification method mainly including extraction with pH 1.0 distilled water and then desorption with pH 1.0 95% ethanol after a DM-130 resin adsorption step to obtain more pure anthocyanins extracts, the purity of anthocyanins extract from S. nigrum fruits reached to 56.1%. Moreover, eight anthocyanins from S. nigrum fruit were identified with HPLC-MS/MS for the first time. A typical R2R3-MYB transcription factor gene, SnMYB, was also cloned for the first time by RACE-PCR from S. nigrum. Moreover, the contents of anthocyanins was shown a good correlation (r = 0.93) with the expression levels of SnMYB during the fruits developmental stages. Most significantly, SnMYB successfully produced high anthocyanins contents (1.03 mg/g) when SnMYB was transiently expressed in tobacco leaves. Taken together, S. nigrum fruits are a promising resource for anthocyanins extraction and SnMYB is an activator that positively regulates anthocyanins biosynthesis in S. nigrum.