The current work reveals the fine tuning between stability zones and randomness of GI/M/1 Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary D/M/1 queueing system. More specifically, this clearly provides more insights into developing a contemporary PSFFA theory that unifies non-stationary queueing theory with chaos theory and fields in both theoretical physics and chaotic systems. This opens new grounds for stability analysis of non-stationary queueing systems. A notable application of GI/M/1 queueing model to achieve ultra-low latency of autonomous driving service is highlighted. Concluding remarks associated with future avenues of research are given.

The theories of Evolution and Big Bang have brought a major impact upon the scientific and societal perception upon the origins, abilities and roles of mankind on Earth. It is conclusively evident that Mother Nature and the physical realm is autonomous and all phenomena in the world occur without an imposition against the “free will” of such events and patterns. Nevertheless, this extent of freedom does not imply that life on Earth represents an accident and has no purpose. By careful analysis of ancient religious texts, it can be suggested even otherwise, that it is especially free will that is offered as a gift from outside of the physical dimensions of existence, with the purpose of a continuous edification and improvement of the overall life conditions and of the human perception. It may be that the multi-generational focus on improvement and progress have been misattributed as a long-term evolution of species, that humans came from animal ancestors and that there is a blurred line associating humans with animals. Furthermore, it may be that scientists based their suggestions that no outside Creator would have brought the Earth into existence on physical perspectives, when the extra-dimensional process of Creation implies that all elements of the physical existence undergo a process of Creation from the outside, where time, space and physical matter do not exist, in spite of such elements possibly reflecting unseen elements of the meta-physical world. Finally, there is the following example that deserves attention within the scientific community; just because all living cells - human, animal and plant - contain DNA chromosomes, ribosomes, mitochondria and a plasma membrane, it does not indicate that humans are animals, just as this does not indicate that plants are animals. In Science, there is a golden statement, that correlation does not imply causation. This example is in complete agreement with the verses of the Book of Genesis in the Holy Scriptures regarding the origins of life; namely, that animals could have been created by an Author of all life on Earth so that man would experience companionship. Another major accordance with the teachings of the Holy Scriptures is the fact that life emerged from the water, and not from the soil, although the soil constituted the second principal means of the commencement and extension of life. Namely, after life first emerged in the seas and the oceans from bacteria, a few bacteria were passed from the marine water into the nearby soil on islands and surrounding land through the circulatory air above the sea level. Afterward, the first life forms emerged from the soil, via the transferred bacteria. Eastern Orthodox Christianity regards water as the principal environment of both physical and spiritual birth. Overall, an improved scientific perception of the timeline of life on Earth may be reached via an approach that combines molecular biology with quantum physics, given that the three layers of Science - Biology, Chemistry and Physics - together with their foundational layer of Mathematics, are in fact situated in a relationship of complete harmony.

A comprehensive evaluation system of rural building energy consumption from a innovative composite perspective is established, which is suitable for southwest China. the brainstorming method and Delphi method were used to establish the indicator system, the ANP method was applied to calculate the weights of the comprehensive evaluation model, the scoring criteria of all evaluation indexes are constructed based on fuzzy evaluation theory, the applicability of the model is verified by an example of the countryside around Chengdu. The results showed that the score of some factors is low, whole or part area, just like the percentage of clean energy use(C24), the thermal performance of external walls(E21), the implementation of energy-saving measures(S22), were key factors affecting the target level, which has greater potential for improvement. The distribution of comprehensive indicators and evaluation factors have certain spatial distribution characteristics, the overall spatial distribution shows the characterwastic of "high in the southeast and low in the northwest". The key factors and spatial distribution characteristics found can be used as an important basis for the improvement of green energy-saving promotion measures, energy-saving retrofit programmes were proposed in terms of additional solar room, energy-saving of external walls and air-conditioning temperature setting guidance.

In this study, MBBR, utilizing kaldnes as a media to attach and grow microorganisms, was used to treat organics in a Compact Septage Treatment Plant (CSTP). Seeding and acclimatization processes were done initially to ensure the microorganisms were able to grow and adapt well within their environments. This research was done to determine the time required for those processes, the optimum conditions, and the growth mechanism of microorganisms during the acclimatization process. Both processes were run in a batch mode. Changes in colour and weight of kaldnes were analyzed for the seeding stage; while COD, MLVSS, pH & temperature were observed for the acclimatization stage. Seeding and acclimatization were run for 6 and 16 days respectively. Acclimatization stage was halted when MLVSS, pH, temperature and COD reduction efficiency were stable. Three phases of microorganism growth were clearly observed in the end of the acclimatization stage, i.e., lag, constant increasing and declining rates. This indicated that microorganisms could adapt well with the MBBR system, and were ready to be utilized further to treat septage in the MBBR of the CSTP. Further research is required to investigate the efficacy of the MBBR with the acclimatized microorganisms in the CSTP.

The domain of construction engineering and management is evolving rapidly. Optimizing resource positioning is crucial for meeting the challenges of efficiency and productivity. This research presents a novel methodology that incorporates Agent-Based Modeling (ABM), Building Information Modeling (BIM), and Bluetooth Low Energy (BLE) technologies, augmented with a Client Early Warning System (CEWS) and a Decision Support System (DSS). What makes this study unique is that it provides a real-time methodology for resource allocation and project management, tailored to address the complexities of modern construction projects. The application of this integrated technological framework marks a significant leap in construction management, empowering data-driven decision-making and significantly improving project efficiency. Empirically validated through a case study at Helwan University's College of Engineering and substantiated by expert surveys, this research showcases a transformative model for resource management. The findings not only underscore the practical applicability of this approach but also open new horizons for its adoption in global construction practices, offering insights for future research endeavors focused on expanding these methodologies to a wider range of resources.

CO2 geological sequestration in coal seams can achieve the dual objectives of CO2 emission reduction and enhanced coalbed methane production, making it a highly promising carbon capture and storage technology. However, the injection of CO2 into coal reservoirs in the form of supercritical fluid (ScCO2) leads to complex physicochemical reactions with the coal seam, altering the properties of the coal reservoir and impacting the effectiveness of CO2 sequestration and methane production enhancement.In this paper, theoretical calculations based on ReaxFF-MD were conducted to study the interaction mechanism between ScCO2 and the macromolecular structure of both low-rank and high-rank coal, to address the limitations of experimental methods. The reaction of ScCO2 with low-rank coal and high-rank coal exhibits significant differences. At swelling stage, the low-rank coal experiences a decrease in aromatic structure and aliphatic structure, high-rank coal shows an increase in aromatic structure and a decrease in aliphatic structure, while swelling phenomenon is more pronounced in high-rank coal. At dissolution stage, low-rank coal is initially decomposed into two secondary molecular fragments, and then recombine to form new molecular structure, the aromatic structure increased and the aliphatic structure decreased. In contrast, high-rank coal occurs stretches-breakage-movement-reconnection, a reduction in aromatic structure and an increase in aliphatic structure.The primary reasons for these variations lie in distinct molecular structure compositions and the properties of ScCO2, leading to different reaction pathways of functional group and aromatic structure. The reaction pathways of functional groups and aromatic structures in coal can be summarized as follows: the breakage of the O-H bond in hydroxyl groups, the breakage of the C-OH bond in carboxyl groups, transformation of aliphatic structures into smaller hydrocarbon compounds or formation of long-chain alkenes, and various pathways involving broken, rearrangement, recombination of aromatic structures. In low-rank coal, there is a higher abundance of oxygen-containing functional groups and aliphatic structures. The breakage of O-H and C-OH chemical bonds results in the formation of free radical ions, while some aliphatic structures detach to produce hydrocarbons. Additionally, some of these aliphatic structures combine with carbonyl groups and free radical ions to generate new aromatic structures. Conversely, in high-rank coal, the lower content of oxygen-containing functional groups and aliphatic structures, along with stronger intramolecular forces, results in fewer chemical bond breakages and makes it less conducive to the formation of new aromatic structures.These results elucidate the specific deformations of different chemical groups, offering a molecular-level understanding of the interaction between CO2 and coal.

In recent years, the rapid expansion of urban areas has led to changes in land use, a reduction in pervious surfaces, and a disturbance in the balance between surface waters and groundwater. These urban changes, combined with inadequate drainage systems and misdirection of runoff, have resulted in severe urban floods, causing numerous fatalities and damage to urban areas. As a result, investigating the effects of flood occurrences and determining proper mitigation measures to reduce flood damage is essential. This paper aims to establish a novel economic-hydrologic model to evaluate the efficacy of Low-impact Development (LID) measures in urban Bronx River catchment, NYC. The model examines reduced peak discharge of flood and imposed damage. Initially, the EPA’s SWMM is used to simulate urban flooding based on recent extreme events. LID scenarios are then implemented, including individual and combined scenarios, to mitigate the adverse impacts of flood occurrences of high to low frequency. By means of the HEC-GeoRAS tool, highly detailed flood inundation maps are generated and seamlessly incorporated into the flood damage estimation model, namely HAZUS, to obtain estimates of the potential damage caused by floods. Using the reduced monetary damages and the implementation cost of LID measures, the benefit-to-cost (BC) ratio is then calculated. Findings indicated that the combined LID scenario is the most effective approach in peak flow reduction. Moreover, Permeable pavement outperforms infiltration trench, bio retention cell, and rain barrel in terms of benefit-to-cost ratio, with rain barrel showing the lowest ratio. The proposed evaluation system for LID measures, with a focus on flood damage reduction as a key benefit, provides valuable insights for identifying optimal scenarios and facilitating informed decision-making.

In the quest for more efficient solar thermal systems, accurately determining the thermal emittance of low-emissive materials is crucial in determining the power losses. This paper describes the calorimetric method designed to precisely measure the thermal emittance of Selective Solar Absorbers (SSAs) to be used in High Vacuum Flat Plate Collectors (HVFPCs). The method's capability is demonstrated through the successful correction of thermal emittance values for copper samples of varying sizes, including dimensions down to 49 cm². Results highlight the method's potential to significantly reduce measurement errors associated with small-size and/or low-emittance samples, providing a path forward to improve the design and efficiency of SSAs. This research marks a significant step in advancing solar thermal technology by enabling emittance measurements with a precision better than 0.003, which is essential for the development of high-performance solar thermal absorbers. The method has also been applied to correct the thermal emittance value of SSA measured in previous measurement campaigns, and it allows a better estimation of the SSA efficiency conversion curve.

This study addresses the importance of conducting mass movement susceptibility mapping and hazard assessment using quantitative techniques, including machine learning, in the Northern Lima Commonwealth (NLC). Previous exploration of the topographic variables revealed high correlation and multicollinearity among some of them, which led to dimensionality reduction through principal component analysis (PCA). Six susceptibility models were generated using weights of evidence, logistic regression, multilayer perceptron, support vector machine, random forest, and naive Bayes methods to produce quantitative susceptibility maps and assess the hazard associated with two scenarios: the first being an El Niño phenomenon and the second being an earthquake exceeding 8.8Mw. The main findings indicate that machine learning models exhibit excellent predictive performance for the presence and absence of mass movement events, as all models surpassed an AUC value of >0.9, with the random forest model standing out. In terms of hazard levels, in the event of an El Niño phenomenon or an earthquake exceeding 8.8Mw, approximately 40% of the NLC area would be exposed to the highest hazard levels. It also highlights the importance of integrating methodologies to reduce model uncertainty, such as comprehensive analysis of variables supported by high quality data and organized workflows. The findings of this research are expected to serve as a supportive tool for land managers in formulating effective disaster prevention and risk reduction strategies.

It is well known that the effect of laser irradiation on the blood causes a change in the shape of red blood cells and an increase in their activity, especially in low-level laser therapy (LLLT). The aim of this study was to identify the ability of erythrocytes to deform when exposed to a blue laser.24 laboratory rats were exposed to blue laser in the gingival region of the lower jaw daily for 5 minutes over 3 days. The blue laser possessed a power of 0.5 W and was operated using a con-tactless approach, the dynamic technique in continuous wave mode, and an uninitiated fiber. A blood sample was taken from the lateral vein of the tail before the LLLT, on the first, second, third, and fifth days. The samples were stained, and cytometry was conducted. The exposure to blue laser caused a significant increase in the number of dome-shaped deformable erythrocytes in the blood of laboratory rats (p

In this paper we present a city-scale (possibly global) air pollution network made of low-cost sensors for particulate matter concentration in the air. The components of presented system are based on our research and experience from previous studies focused on air quality instruments and sensors for addressing urban air pollution. Sensor nodes are produced locally and distributed over a city of Sarajevo, Bosnia and Herzegovina. The system collects, calibrates and displays particulate metal concentrations in real-time. In comparison to the available measurements from governmental institutions, our system demonstrated good agreement of measured parameters, with several advantages including: higher resolution in space and time, lower costs, both horizontal and vertical measurements and many more. One of the capabilities of the system is the real-time air pollution city map with animations. By installing multiple sensor nodes over a slope (cable car), we receive vertical measurements of temperature, humidity and particulate matter concentration in real time, which gives a valuable insight into the dynamics of temperature inversion episodes and air pollution below the inversion layer.

The prolonged static sitting at the workplace is considered as one of the main risks for development of musculoskeletal disorders (MSDs) and adverse health effects. Factors such as poor posture and extended sitting are perceived to be a reason for conditions such as lumbar hyperlordosis and lower back pain (LBP), even though the scientific explanation of this relationship is still unclear and raises disputes in the scientific community. This publication proposes the low back pain assessment (LBPA) dataset collected through experiment with 100 participants and consisting of photogrammetric images with intentionally placed body markers, calculated postural angles and tags correct and incorrect posture assessed by habilitated rehabilitator, as well as questionnaire-based self-reports regarding the occurrence of LBP and similar symptoms among the participants. Machine learning models trained with this data are employed for recognizing incorrect body postures. Two scenarios have been elaborated for modeling purposes: scenario 1, based on natural body posture tagged as correct and incorrect, and scenario 2, based on incorrect body postures, corrected additionally by the rehabilitator. The achieved accuracies of respectively 75.3% and 85% for both scenarios reveal the potential for future research in enhancing awareness and actively managing posture-related issues that elevate the likelihood of developing lower back pain symptoms.

Background: Gender differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, gender-specific analysis remains underexplored. This retrospective study aimed to evaluate the gender-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods: Data were collected from 47 patients (31 women, 16 men), with age > 18 years, BMI ≥ 30 kg/m^2, absence of T2D, and with exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results: Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, % WL, WL >5% and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant gender differences were observed in glucose metabolism or renal function. Conclusion: This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

The efficacy and cost-effectivness of Multigene Panel Next-Generation Sequencing (NGS) in directing patients towards genomically matched therapies remains uncertain. This study investigated metastatic colorectal cancer (mCRC) patients who underwent NGS analysis on formalin-fixed paraffin-embedded tumor samples. Data from 179 patients were analyzed, revealing no mutations in 39 patients (21.8%), one mutation in 83 patients (46.4%), and two or more mutations in 57 patients (31.8%). KRAS mutations were found in 87 patients (48.6%), including KRAS G12C mutations in 5 patients (2.8%), PIK3CA mutations in 40 patients (22.4%), BRAF mutations in 26 patients (14.5%). Less common mutations were identified: ERBB2 in 5 patients (2.8%) and SMO in 4 patients (2.2%). Additionally, MAP2K1, CTNNB1, and MYC were mutated in 3 patients (2.4%). Two mutations (1.1%) were observed in ERBB3, RAF1, MTOR, JAK1, and FGFR2. No significant survival differences were observed based on mutation numbers. 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.

This study assessed the performance of low-dose CT lung scans across various acquisition parameters and examined the impact of iterative reconstruction (IR) algorithms on image quality for lung cancer screening. The performance of multi-slice CT scanners was assessed by using a Catphan 600 phantom, specifically within the CTP404 test module that contains materials like Teflon, Delrin, Acrylic, Polystyrene, LDPE, PMP, Air, and water. Three protocols were selected and categorized into standard, low dose, and ultra-low dose. The standard protocol featured a tube voltage of 100 kVp for single-detector CT, a pitch of 0.75, detector collimation of 0.60 mm, and a gantry rotation time of 0.33 seconds, with 5 mm slice thickness. Images were reconstructed using standard kernels like B80f and 170f, combined with either FBP or various IR algorithms. Findings indicated that the noise power spectrum (NPS) peak value (HU2mm2) increased with higher IR levels, with FBP showing the highest peak. Additionally, NPS spatial frequency diminished as IR levels rose. Optimizing contrast and spatial resolution for both background and regions of interest involved adjusting the target transfer function (TTF) and contrast-to-noise ratio (CNR), crucial for protocol optimization. Proper adjustment of IR levels is vital, as higher levels can alter image texture and affect NPS spatial frequency. The results of this study showed that the use of IR algorithms in low-dose CT lung scans significantly improved image quality, particularly in terms of noise reduction and spatial resolution. However, the choice of acquisition parameters also played a crucial

Preschoolers with disabilities and their family caregivers are missed out in many public health initiatives especially in low-income countries. Yet they can benefit from early intervention to promote their development from soon after birth and to provide a better quality of life for their families. In this paper, we describe how a community-based approach has been implemented with minimal funding in two areas in Zimbabwe: a township in Harare and in rural areas of Manicaland Province. Our aim in sharing this information – allied with references to research studies recently undertaken in Africa – is that it will enable similar supports to be replicated in other communities by local personnel. A logic model is used to describe the situation in which the two projects work, the various inputs they have provided to their community and the different forms of support they have offered to the children and their caregivers. The project outputs are listed in terms of the number of beneficiaries helped and activities undertaken. The outcomes achieved for the children, the family and communities are reported. The sustainability and extensions of community-based projects to address unmet needs are discussed. The main conclusion is that disadvantaged communities can be energized to address the needs of their most marginalized residents.

Myelolipoma is a benign, typically inert neoplasm of uncertain aetiology that is rarely reported in cats. Although commonly asymptomatic, in some cases, myelolipomas can cause abdominal discomfort or present with rupture and haemorrhage. Here, we describe a rare case of a splenic myelolipoma in a Domestic Long Hair cat in which, after extensive diagnostic investigations, clinical signs of hyporexia and weight loss were attributable to the presence of an intra-abdominal mass. The patient was treated by splenectomy and unexpectedly died during the post-operative period. Although splenectomy appears to be a sensible intervention in symptomatic patients, the optimal management of splenic myelolipomas in cats remains unknown. The risk-benefit ratio of surgical management needs to be carefully considered, and therapeutic intervention should be tailored individually to each patient.

In this work, an analog front-end (AFE) circuit for Electrocardiogram (ECG) detection system has been designed, implemented, and investigated in an industry-standard Cadence simulation framework using advanced technology node of 45 nm. The AFE consists of an instrumentation amplifier, a Butterworth band-pass filter (with fifth-order low-pass and second-order high-pass sections), and a second-order notch filter- all are based on two-stage, Miller-compensated operational transconductance amplifiers (OTA). The OTAs have been designed employing the $g_m/I_D$ methodology. Both the pre-layout and post-layout simulation were carried out. The layout consumes an area of 0.0058 mm$^2$ without the resistors and capacitors. Analysis of various simulation results were carried out for the proposed AFE. The circuit demonstrates a post-layout bandwidth of 239 Hz with a variable gain between 44 to 58 dB, a notch depth of -56.4 dB at 50.1 Hz, a total harmonic distortion (THD) of -59.65 dB (less than 1\%), an input referred noise spectral density of $

It’s well known that existing horizontal well drilling and hydraulic fracturing technology that is used to achieve large-scale cost-effective production from immature to low-moderate maturity continental shale in China, where the organic matter mainly exists in the solid form is fairly ineffective. To overcome the obstacles, in-situ conversion technology seems feasible, while implementing it in the target layer along with estimating the amount of expected recoverable hydrocarbon in such shale formations seems difficult. This is because there is no guideline to choose the most appropriate method and select relevant key parameters for this purpose. Hence, based on thermal simulation experiments during the in-situ conversion of crude oil from the Triassic Chang 73 Formation in the Ordos Basin and the Cretaceous Nenjiang Formation in the Songliao Basin, this deficiency in knowledge was addressed. First, relationships between the in-situ converted total organic carbon (TOC) content and the vitrinite reflectance (Ro) of the shales and between the residual oil volume and the hydrocarbon yield was established. Second, the yields of residual oil and in-situ converted hydrocarbon were measured, revealing their sensitivity to fluid pressure and crude oil density. In addition, a model was proposed to estimate the amount of in-situ converted hydrocarbon based on the TOC, hydrocarbon generation potential, Ro, residual oil volume, fluid pressure, and crude oil density. Finally, a method was established to determine key parameters on the final hydrocarbon yield from immature to low-moderate maturity organic material during in-situ conversion in shales. Following the procedure outlined in this paper, estimated recoverable in-situ converted oil in the shales of the Nenjiang Formation in the Songliao Basin was estimated to be approximately 292×108 tons, along with 18.5×1012 cubic meters of natural gas, in an area of approximately 8×104 square kilometers. Collectively, the method developed in this study is independent from the organic matter type and other geological and/or petrophysical properties of the formation and can be applied to other areas globally where there isn’t any available in-situ conversion thermal simulation experimental data.

Coal bottom ash (CBA) is a byproduct of coal-burning power plants. This material can be used as a fine aggregate replacement in concrete to reduce global natural material depletion. Concrete usage is increasing rapidly; subsequently, the industry’s carbon footprint is increasing. Using CBA in the construction industry will reduce the technical and economic problems associated with power plants by reducing solid waste. This project aimed to determine if adding new sustainable materials, such as CBA, to concrete will reduce natural raw material usage, energy consumption, and greenhouse gas emissions while improving performance. This study included two projects: comparing increased CBA content to the two-control project and determining the optimum content based on the compressive strength. The optimum CBA content is 50%, which reduces fine aggregate usage in a concrete mix by 50% while maintaining equivalent or better concrete strength than a pure Portland concrete mix without CBA. The air content of the concrete mix containing % CBA decreased with increased CBA content and compressive strength, possibly due to the spacing factor of the voids in the mix and CBA’s porous and fineness behavior. The CBA optimum content had a unit weight lower than the controls for both projects, which makes the CBA mix a lightweight concrete. Using this material can significantly reduce natural material usage and environmental harm by reducing CBA waste disposal and improving concrete performance.

This study presents a detailed computational investigation aimed at identifying and evaluating potential small organic molecular scaffolds as inhibitors targeting the Pks13 protein, a critical enzyme in tuberculosis (TB) drug discovery. Our approach integrates multiple computational techniques, including quantitative structure-activity relationship (QSAR) modelling, compound library generation, molecular docking, biological activity prediction, re-evaluation of screened compounds, molecular dynamics (MD) analysis, and binding free energy estimation using the MM-GBSA approach. We developed a robust QSAR model using multiple linear regression (MLR) techniques, specifically tailored to predict the minimum inhibitory concentration (MIC) values of potential anti-TB agents. This model demonstrated excellent predictive performance, validated through rigorous internal and external validation procedures. Through molecular docking simulations, we identified five promising inhibitors Ethyl (R,Z)-2-(2-((2-chlorobenzyl) oxy)benzylidene)-5-(4-chlorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo [3,2-a] pyrimidine-6-carboxylate (PKD1), (7R,9aR)-7-(2-hydroxyphenyl)-4-(2-methoxyphenyl)-3-methyl-7,8,9,9a-tetrahydroisoxazolo[5,4-b]quinolin-5(6H)-one (PKD2), (7-(4-methoxy phenyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-yl)(4-(3-(trifluoromethyl)phenyl) piperazin-1-yl)methanone (PKD3), (8S,10S)-10-(((2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl tetrahydro-2H-pyran-2-yl)oxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetra-hydrotetracene-5,12-dione (PKD4), 3-(3,4-dimethylphenyl)-5-((2-(4-fluorophenyl)-2-oxoethyl) thio)-6-phenyl-2-thioxo-2,3,5,7a-tetrahydrothiazolo[4,5-d]pyrimidin-7(6H)-one (PKD5)with high binding affinities, prioritizing them based on their binding energies. These selected compounds were further assessed for their biological activity predictions, guiding the selection of candidates for experimental validation. Subsequent re-evaluation using absolute binding free energy estimation and MD simulations provided insights into the stability and dynamics of the protein-ligand complexes over time. Our findings highlighted the potential of identified compounds as stable binders within the Pks13-TE domain binding pocket, underscoring their viability as drug candidates. Additionally, binding free energy analysis using MM-GBSA reaffirmed the strong affinity of the proposed compounds towards Pks13. Our integrated computational approach offers a systematic and detailed framework for the identification and characterization of potential Pks13 inhibitors with specific relevance to TB drug discovery.

Increasingly large numbers of people are using digital weight-loss services (DWLSs) to treat overweight or obesity. Although it is widely agreed that digital modalities improve access to care in general, obesity stakeholders remain concerned that many DWLSs are not comprehensive or sustainable enough to deliver meaningful health outcomes. This study adopted a mixed-methods approach to assess why and after how long patients tend to discontinue Austral-ia’s largest DWLS, a program that combines behavioural and pharmacological therapy under the guidance of a multidisciplinary care team. We found that in a cohort of patients who commenced the Eucalyptus DWLS between January and June 2022 (n=5604), mean program adherence was 171.2 (±158.2). Inadequate supply of a patient’s desired Glucose-like peptide-1 receptor agonist medication was the most common reason for discontinuation (43.7%), followed by program cost (26.2%), result dissatisfaction (9.9%), and service dissatisfaction (7.2%). Statistical tests revealed that ethnicity and age both had a significant effect on patient adherence. These findings suggest that DWLSs have the potential to improve access to comprehensive, continuous obesity care, but that care models need to improve upon the one observed in the Eucalyptus Australia DWLS to maximise program adherence.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Worldwide emission standards are now required to cover engine operation under extreme ambient conditions, which affect the raw emissions and the efficiency of the exhaust aftertreatment systems. These regulations also target new combustion technologies for decarbonization, such as neat hydrogen (H2) combustion or dual-fuel strategies, which involve a challenge to the analysis of exhaust aftertreatment systems requirements and performance. This work addresses the impact of high altitude and low ambient temperature conditions on the reactivity of an oxidation catalyst in the presence of H2. A reaction mechanism is proposed to cover the main conversion paths of CO, HC, and H2, including the formation and consumption of high-energy surface reaction intermediates. The mechanism has been implemented into a faster-than-real-time reduced-order model for multi-layer washcoat honeycomb catalytic converters. The model was utilized to investigate the effect of H2 concentration on the reactivity of CO and HC within the catalyst under various operating and ambient conditions. By applying the model and examining the selectivity towards different reaction pathways in the presence H2, insights into surface intermediates and reactivity across different cross-sections of the monolith were obtained. This analysis discusses the underlying causes of reactivity changes promoted by H2 and its relative importance as a function of driving boundary conditions.

Uncertainties in initial water saturation and early water breakthroughs of un-known sources and paths, which occurred in the low resistivity Lower Haushi sand-stone (LHS) reservoir at the beginning of oil production, imply that the bypassed oil can yet remain in the reservoir. In addition, the upper part of LHS is a tight oil reser-voir, which can still contain a significant amount of unrecovered oil. This opens the opportunity to produce the remaining oil instead of abandoning this reservoir. Low resistivity can exaggerate water saturation, leading to misinterpretation and premature water flooding due to inadequate oil-water contrast. Our analysis revealed a correlation between low resistivity and robust porous network connectivity, along-side elevated formation water salinity in highly porous layers. In regions of high po-rosity, sufficient oil-water contrast facilitates precise water saturation determination, affirming oil presence in all wells. However, within tight oil zones, near-complete wa-ter saturation contradicts actual oil presence. Factors contributing to saturation un-certainty and water breakthroughs were reassessed. Utilizing a 1:1 verti-cal-to-horizontal permeability ratio derived from core data enhanced simulation alignment with water production rates. Investigation into the impact of relative per-meabilities on water production was conducted. Water saturation maps were gener-ated to pinpoint remaining oil reserves. Depletion around wells is evident in lower po-rous regions, while oil persists across the entire tight reservoir, notably in two unex-plored sections.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

In this study, the fundamentals of electroencephalography signals, their categorization into frequency sub-bands, the circuitry used for their acquisition, and the impact of noise interference on signal acquisition are examined. Additionally, design specifications for medical-grade and research-grade EEG circuits and a comprehensive analysis of various analog front-end architectures for electroencephalograph (EEG) circuit design are presented. Three distinct selected case studies are examined in terms of comparative evaluation with generic EEG circuit design templates. Moreover, a novel one-channel battery-supplied EEG analog front-end circuit designed to address the requirements of usage protocols containing strong com-pound muscle movements is introduced. Furthermore, a realistic input signal generator circuit is proposed that models the human body and the Electromagnetic Interference from its surroundings. Experimental simulations are conducted in 50 Hz and 60 Hz electrical grid environments to evaluate the performance of the novel design. The results demonstrate the efficacy of the proposed system, particularly in terms of bandwidth, portability, common mode rejection ratio , gain, suppression of muscle movement artifacts, electrostatic discharge and leakage current protection. Conclusively, the novel design is cost-effective and suitable for both commercial and research single-channel EEG applications. It can be easily incorporated in Brain Computer Interfaces and neurofeedback training systems.

The built environment sector’s growing impact on climate change is becoming increasingly important due to its share in energy consumption and greenhouse gas emissions. Global efforts have been undertaken to design and develop residential dwellings that aim towards zero energy and carbon emission, but there remains a multitude of obstructions to efficient construction processes. This study is focused on the gaps and barriers that have emerged during the pre-construction phase of a low-environmental-impact Passive House in Fayetteville, Arkansas. The technical, management, regulatory, and supply chain obstacles to the construction of a new three-story residential Passive House are documented to engage knowledge transformation in the design and construction of sustainable buildings of interest to developers and property owners. Primary data are collected by direct observation as well as open-ended interviews and secondary data collected through a literature review to understand the barriers and gaps faced by different key actors during the pre-construction phase in different regions. This local study highlighted the lack of interest, knowledge, and experience in sustainable building design among professionals having a significant influence on the project goals and timeline and was mentioned by participants as a common barrier as well as the inconsistency and inadequacy of regulatory framework of existing building codes to implement sustainable building design. These barriers along with other identified barriers are discussed and recommendations to overcome these barriers are provided.

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treat-ment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obe-sity in patients with or without T2DM (liraglutide – LIR, semaglutide - SEM, and tir-zepatide - TIR). Social media had an important influence on the off-label use of GLP-1 RAs for obesity, especially for SEM. We analysed the Google queries related to SEM to assess people's interest in this drug. We also investigated the occurrence of adverse drug reactions (ADRs) by searching the EudraVigilance database (EV) for Individual Case Safety Reports (ICSRs) that reported SEM as the suspected drug and performed a descriptive and a disproportionality analysis. Data obtained for SEM were compared to other GLP-1 RAs. SEM had the highest proportions of searches on Google associated with the term “weight loss” and presented the lowest number of severe ADRs, but it also had the highest number of ICSRs reported in EV. Even though no unexpected safety issues have been reported for it until now, SEM has a high tendency for overdose reports. The most frequent off-label use was reported for SEM and TIR. In order to lower the ADRs’ risks, the off-label use should be reduced and carefully monitored.

Precise classification of sarcomas is crucial to drive optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC) we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was per-formed to all samples, using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed on the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary on molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for the optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance toward a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098−3.97 μM (0.066−2.68 μg mL−1), and comparable to the best-reported medicines. Fe-TMPP can forms stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, a potent inhibitor targeting the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interact with SARS-CoV-2 Mpro(A). Calculations using density functional theory have been instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding with a root mean square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.

Histones are keys to many epigenetic events and their complexes have therapeutic and diagnostic importance. The determination of the structures of histone complexes is fundamental in the design of new drugs. Computational molecular docking is widely used for the prediction of target-ligand complexes. Large, linear peptides like the tail regions of histones are challenging ligands for docking due to their large conformational flexibility, extensive hydration, and weak interactions with the shallow binding pockets of their reader proteins. Thus, fast docking methods often fail to produce complex structures of such peptide ligands at a level appropriate for drug design. To answer this challenge, and improve the structural quality of the docked complexes, post-docking refinement has been applied using various molecular dynamics (MD) approaches. However, a final consensus has not been reached on the desired MD refinement protocol. In the present study, MD refinement strategies were systematically explored on a set of problematic complexes of histone peptide ligands with relatively large errors in their docked geometries. Six protocols were compared that differ in their MD simulation parameters. In all cases, pre-MD hydration of the complex interface regions was applied to avoid the unwanted presence of empty cavities. The best-performing protocol achieved a median of 32 % improvement over the docked structures in terms of the change of root mean squared deviations from the experimental references. The influence of structural factors and explicit hydration on the performance of post-docking MD refinements was also discussed to help their implementation in future methods and applications.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

Several Lung diseases can result in lung damage structural changes, with lung transplantation as a only therapeutic option when the disease reaches an advanced progression, unfortunately, the success of lung transplantation is limited. In this context, lung bioengineering is considered a potential therapeutic alternative and the current approach is based on the use of the natural extracellular matrix (ECM) of the decellularized lung. The use of undifferentiated cells to seed an ECM can be a more practical strategy for lung bioengineering but the sterilization of the organ for this recellularization process is still a challenge. In this sense, Low-Level Laser Therapy (LLLT) can emerge as a potential treatment alternative. Therefore, the objective of this study was to verify if LLLT, can optimize lung recelularization with mesenchymal stem cells by cytokine modulation. For this, we decellularized lungs from C57BL/6 mice perfusing SDS 1% via pulmonary artery, sterilized with LLL (660nm, 100mW, 30s). Whole lung scaffolds were recellularized: (1) Recellularized Lung (2) Recellularized Lung + LLLT. Mesenchymal stem cells derived from human tooth pulp (DPSc) were seeded into lungs and incubated for 24 hours at 37ºC, 5% CO₂, in a bioreactor-like conditions, maintaining CPAP at 20cmH2O, 90% O2, and LLL at wavelength of 808nm, 100mW, 30s. Culture medium were analyzed at 24 hours. H&E, immunostaining, SEM and ELISA assay were performed. We produced viable biological scaffolds absent of DNA content, preserving glycosaminoglycans and collagen I, III and IV, fibronectin, laminin and elastin and lung structure (SEM). The levels of IL-6 and IL-8 were stable during the 24 hours of culture. IFN-γ levels showed significant difference in the DPSc and DPSc+LLLT group in the 24-hour evaluation. The levels of IL-10 decreased after LLLT. These findings highlight LLLT's role in cytokine regulation and contamination prevention during lung recellularization with mesenchymal stem cells. Overall, these results demonstrated that LLLT's modulated cytokine levels and could prevent contamination during the lung recellularization process with mesenchymal stem cells, offering promise for enhanced therapeutic strategies in lung bioengineering

Hyperuricemia is mainly caused by the overproduction of uric acid (UA) catalyzed from xanthine by xanthine oxidase (XO) in abnormal purine metabolism in human body. There is an increasing demand for developing novel XO inhibitors of plant origins. The inhibition kinetics and type as well as actions of hesperetin against XO were investigated in vitro using multi-spectroscopic methods including UV-Vis absorption, Fourier transform infrared spectroscopy (FT-IR), fluorescence spectroscopy and molecular docking simulation. Results indicated that hesperetin reversibly inhibited XO in a competitive manner with an inhibition constant (Ki) value of (2.15 ± 0.05) × 10-6 mol/L. Hesperetin had a higher scavenging rate against O2- radical generated by the XO reaction system. The binding of hesperetin to the active site of XO altered the protein’s secondary structure as demonstrated by FT-IR and fluorescence spectra. Molecular docking study revealed that hesperetin had highly affinity to XO and the bonding of hesperetin to the molybdopterin (Mo-pt) active center inhibited not only substrate entry, but also prevented oxygen binding to flavin adenine dinucleotide (another active center in XO). Additionally, hydrophobic interactions and hydrogen bonds contributed to the stabilization of the hesperetin-XO complex. The results suggested that hesperetin be a promising natural XO inhibitor to alleviate hyperuricemia and gout.

Bigeye grunt Brachydeuterus auritus is an important economic species in the waters off Sierra Leone in West Africa, with great ecological value. Based on the survey data of bottom trawl nets from 6 voyages from 2019 to 2021, the body weight-length relationship (WLR), as well as their relative fatness, were studied in depth using the method of body length and its corresponding mean body weight. This study fitted the WLR of bigeye grunt by gender, calculated its fullness, and analyzed the influence of environmental factors. The results showed that month and gender had a significant impact on body length and weight distribution (P<0.01). There was a highly significant negative correlation (P<0.01) between the condition factor (a) and the allometric factor (b) in the WLR, and salinity significantly affects b (P<0.05). The (lga)/b ratio was less affected by environmental factors which may be related to the body size and density of the fish. The difference in b between male and female populations was extremely significant (P<0.01). The relative fatness had significant seasonal variation characteristics, with highly significant effects of sex and body length (P<0.01). With increasing body length, the relative fatness showed two types of changes, continuously increasing and first increasing then decreasing, with salinity and b significantly affecting the type of change (P<0.05) and depth having a highly significant effect (P<0.01). The bigeye grunt off the coast Sierra Leone exhibited significant seasonal growth characteristics, with significant differences in growth characteristics between male and female individuals. This study suggested that salinity may be the main factor affecting its growth and development. In addition, this study hypothesised that the peak breeding season may occur during the dry season, beginning in December and ending before April of the following year. The study provides updated and more comprehensive insights into the biology and ecology of the bigeye grunt offshore Sierra Leone, West Africa, which can provide scientific basis for its resource assessment, development and utilization, and resource management.

Accurate clinical diagnosis of patients presenting to primary care settings with acute sore throat remains challenging, often resulting in the over-prescribing of antibiotics. Using point-of-care tests (POCTs) to differentiate between respiratory infections is well-accepted, yet evidence on the application within primary care is sparse. We assessed the application of testing patients (n=160) from three family practices with suspected Streptococcal infections using rapid molecular tests (ID NOW Strep A2, Abbott). In addition to comparing clinical evaluation and prescription rates with either usual care or with testing, patients and staff completed a questionnaire about their experience of molecular POCT in primary care. The immediate availability of the result was important to patients (100%) and staff (≈90%) stated that molecular testing improved quality of care. Interestingly, only 22.73% of patients with a Centor score >2 tested positive for Strep A and overall, less than 50% of Centor scores 3 and 4 tested positive for Strep A with the ID NOW testing platform. The addition of rapid molecular POCTs to clinical assessment resulted in a 55- 65% reduction in immediate and deferred antibiotic prescriptions. The intervention was popular with patients and medical staff but was associated with increased cost and a longer appointment length.

To achieve rapid post-earthquake repair of self-centering ribbed floor flat beam frame structures, a ductile hybrid joint consisting of dog bone weakened energy dissipating steel bars connected to the upper and lower column sections through high-strength threads based on the damage control design concept is proposed. By moving the ductile energy dissipating zone out to the locally weakened section of the energy dissipating steel bars and the locally unbonded prestressed steel bars in the core area, the residual deformation was limited and the seismic performance was improved. Based on the working principle of hybrid joints, low cycle loading tests were conducted on two joint specimens to analyze the influence of lateral prestress on the seismic performance of the hybrid joints. Numerical modeling methods were used to compare the position of the energy-consuming steel bars in the composite layer and the friction performance of joints. The research results indicated that the hybrid joint had stable load-bearing, deformation, and energy dissipation capabilities, with damage primarily concentrated on the energy-consuming steel bars. Even at an inter-story displacement angle of 5.5%, the upper and lower column segments remained elastic. After unloading, the connection seam at the joint was closed, and the self-centering performance was good. When the inter-story displacement angle reached 5.5%, the lateral prestress increased from 150 kN to 250 kN, the ultimate bearing capacity of the joint increased by 16.3%, and the cumulative energy consumption increased by 30.0%. The influence of the friction coefficient of the joint surface on the structural performance was set at a threshold of 0.7. When it was less than the threshold, the ultimate bearing capacity and initial stiffness of the joint increased with an increase in the friction coefficient. After reaching the threshold, the increase in the ultimate bearing capacity of the joint slowed down, and the rate of stiffness degradation gradually accelerated. This joint had excellent seismic performance and can also achieve post-earthquake repair of structures.

Asymmetric lithium salts, such as Lithium (difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (LiDFTFSI), have been demonstrated to surpass traditional symmetric lithium salts with improved Li+ conductivity and the capacity to generate stable solid electrolyte interphase (SEI) while maintaining compatibility with aluminum (Al0) current collector. However, the intrinsic reductive mechanism through which LiDFTFSI influences battery performance remains unclear and under debate. Herein, the detailed SEI reactions of LiDFTFSI-based electrolytes were investigated by combining density functional theory and molecular dynamics, aiming to clarify the formation process and atomic structure of SEI. Our results show that asymmetric DFTFSI– weakens the interaction between carbonate solvents and Li+, and substantially alter the solvation structure, exhibiting a well-balanced coordination capacity to bis(trifluoromethanesulfonyl)imide (TFSI–). Nanoseconds hybrid molecular dynamics simulation further reveals that the preferential decomposition of LiDFTFSI produces sufficient LiF and Li2O to facilitate a robust SEI. Moreover, the abundant F– generated from LiDFTFSI decomposition accumulates on the Al surface and subsequently combines with Al3+ from the current collector to form AlF3, potentially inhibiting corrosion of the current collector. Overall, these findings elucidate how LiDFTFSI regulates the solvation sheath and SEI structure, advancing the development of high-performance electrolytes compatible with current collector.

Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15- 20 % of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is by analysis of tumor biopsies for HER2 expression and amplification. Previously patients were either defined as HER2-positive or negative, however, with approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 and lacking HER2 amplification have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is mo-lecular imaging with radiotracers. In case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Affibody-based radiotracers are clinically validated molecules with favorable characteristics for imaging. In this article we summarize the HER2-targeted therapeutic landscape, describe the experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as novel diagnostic tool in breast cancer and beyond.

Climate change is increasing air temperatures and altering the precipitation and hydrological re-gime on a global scale. Challenges arise when assessing the impacts of climate change on the local scale for water resources management proposes, especially for low mountain headwater catch-ments that not only serve as important water towers for local communities, but also have distinct hydrological characteristics. Until now, no low flow or hydrological drought studies have been carried out on the Lauter River. This study is unique in that it compares the Lauter River, a transboundary Rhine tributary with a nearby station on the River Rhine just below its confluence at the French-German border. The Lauter catchment is a mostly natural, forested catchment, however, its water course has been influenced by past and present cultural activities. Climate change disturbances cascade through the hydrologic regime right down to the local scale. As we are expecting more low flow events, the decrease in water availability could cause conflicts be-tween different water user groups in the Lauter catchment. However, the choice of different methods for identifying low flow periods may cause confusion for local water resources manag-ers. Using flow rate time series of the Lauter River between 1956 and 2022 we compare for the first time three low flow identification methods: the variable threshold method (VT), the fixed threshold method (FT), and the Standardized Streamflow Index (SSI). Similar analyses are applied and compared to the adjacent Maxau station on the Rhine River for the same time period. This study aims at 1) interpreting the differences amongst the various low flow identification methods and 2) revealing the differences in low flow characteristics of the Lauter catchment compared to the Rhine River. It appears that the FT reacts faster to direct climate or anthropogenic impacts whereas VT is more sensitive to indirect factors such as decreasing subsurface flow which is typical for small headwater catchments, such as the Lauter where flow dynamics react faster to flow disturbances. Abnormally low flow during the early Spring in tributaries such as the Lauter can help predict low flow conditions of the Rhine River during the following half year and espe-cially for the summer. The results could facilitate Early Warning of hydrological droughts and drought management for water users in the Lauter catchment and further downstream along some of the Rhine.

Amylose content (AC) stands as a pivotal determinant of rice grain quality, primarily governed by the Waxy gene (Wx), with its allelic diversity significantly influencing AC variation. In the current culinary landscape, soft rice varieties, known for their low AC and superior palatability, are particularly sought after by consumers. Notably, many soft japonica rice varieties cultivated in southern China, including the Nangeng series, are characterized by the presence of the Wxmp allele, derived from the ancestral Wxmq allele. While both alleles are associated with reduced AC, there remains a paucity of detailed understanding regarding the interplay between specific functional single nucleotide polymorphisms (SNPs) within these alleles and the overarching rice grain quality. Employing site-directed mutagenesis, we engineered three distinct transgenic rice lines, each harboring either the Wxmp, Wxmq, or Wxb-5c alleles, against the background of the glutinous rice cultivar Nip(wx). This suite of transgenic rice showcased a gradation ingrain transparency inversely correlated to AC, delineating a sequence from Wxmq, signifying the lowest, through Wxmp, to Wxb-5c, indicating the highest. Consequently, this gradation in AC precipitated variations in other rice grain physicochemical attributes, such as the taste value of cooked rice, gel consistency (GC), and starch pasting properties. Furthermore, analyses of gene expression and enzyme activity revealed that the functional SNPs, Ex4-53G/A and Ex5-53T/C, lead to a decline in the GBSSI enzyme activity without affecting expression levels. These findings underscore the potential of harnessing these SNPs in breeding programs aimed at developing soft rice varieties endowed with enhanced culinary qualities.

Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of available structurally diverse antifungal drug armamentariums. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro antifungal activities of globospiramine against Candida albicans and Candida tropicalis and explore its possible target proteins using in silico methods. The colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid by decreasing almost 50% of the viable CFUs 60 min after treatment. Results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 4 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments indicated stable, strong binding of globospiramine with the target proteins 1,3-β-glucan synthase and Als3 adhesin enzymes, which are indirectly involved in apoptotic-driven candidal inhibition.

The results shown in this paper extend our research group's previous work, which presents the theoretically achievable hydrogen engine-out NOx (H2-NOx) Pareto front of a hydrogen hybrid electric vehicle (H2-HEV). While the Pareto front is calculated offline, which requires significant computing power and time, this work presents an online-capable algorithm to tackle the energy management of a H2-HEV with explicit consideration of the H2-NOx trade-off. Through the inclusion of realistic predictive data on the upcoming driving mission, a model predictive control algorithm (MPC) is utilized to effectively tackle the conflicting goal of achieving low hydrogen consumption while simultaneously minimizing the NOx. In a case study it is shown that the MPC is able to satisfy user-defined NOx limits over the course of various driving missions. Moreover, a comparison to the optimal Pareto front highlights the MPC's ability to achieve close-to-optimal fuel-performance for any desired cumulated NOx target on four realistic routes for passenger cars.

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

The increasing use of Convolutional Neural Networks (CNN) has brought about a significant transformation in numerous fields, such as image categorization and identification. In the development of a CNN model for classifying images of sericea lespedeza (SL; Lespedeza cuneata) from weed images, four architectures were explored: CNN-Model Variant 1, CNN-Model Variant 2, VGG16, and ResNet50. The CNN-Model Variant 1 demonstrated 100 % validation accuracy, while Variant 2 achieved 90.78% validation accuracy. Pre-trained models, like VGG16 and ResNet50, were also analyzed. In contrast, ResNet50's steady learning pattern indicated potential for better generalization. A detailed evaluation of these models revealed that Variant 1 achieved a perfect score in precision, recall, and F1-score, indicating superior optimization and feature utilization. Variant 2 presented a balanced performance, with metrics between 86% and 93%. The VGG16 mirrored the behavior of Variant 2, both maintaining around 90% accuracy, but ResNet50's results revealed a conservative approach for class 0 predictions. Overall, Variant 1 stood out in performance, while both Variant 2 and VGG16 showed balanced results. The reliability of CNN model Variant 1 is highlighted by the significant accuracy percentages, which demonstrate its potential for practical implementation in agriculture. Smartphone application for the identification of SL in a field-based trial has shown promising results with an accuracy of 98%-99%. Using a CNN model with batch normalization has the potential to play a crucial role in redefining and optimizing the management of undesirable vegetation in the future.

Cement production contributes to about 7% of CO2 emissions into the atmosphere. Despite our best efforts, we cannot find a competitive substitute that is both reliable and environmentally friendly. The simplest way to solve the problem is to rationalize the resources and try to minimize its use by substitute them with other materials. A concrete that contains a substantial amount of fly ash is already available, but its use is limited by the current shortage in the market and reduced initial resistance. In this context, ternary mixtures have been used to conduct an experiment. A significant volume of cement has been replaced with fly ash and metakaolin, which serves as a correction factor for the performance. In this work the main advantages and disadvantages of the simultaneous use of these two additions, which may reveal to be very interesting with high volumes of substitution will be presented. The performance of this ternary mixture is very promising. Provide a wide range of possibilities for replacing cement, maintaining or even improving its mechanical and durability properties. A solution for an ecological concrete with enhanced performance for general use in construction as an alternative to conventional concrete.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Tropical rock lobsters (Panulirus ornatus) are a highly cannibalistic species with intermoult animals predominantly attacking animals during ecdysis (moulting). Rapid, positive characterisation of pre-ecdysis lobsters may open a pathway to disrupt cannibalism. Ecdysial suture line development is considered for pre-ecdysis recognition with suture line definition compared for lobsters emerged and immerged, using white, near ultraviolet (365 nm), near infrared (850 nm) and spe-cialty Osram SFH 4737 broadband IR LEDs against a reference of intermoult lobsters with no suture line development. An alternative pre-ecdysis recognition strategy used a novel low-cost spectral camera composed of the Sony IMX219, AMS AS7265x spectral sensors and Osram SFH 4737 broadband infrared LEDs. Images and data using the novel low-cost spectral camera was acquired from intermoult, pre-ecdysis, and post-ecdysis lobsters. Compared with the white light appear-ance, suture line definition was enhanced under 850 nm, 365 nm, and SFH 4737 LEDs for immerged lobsters, while the 850 nm LED achieved the best suture line definition of emerged lobsters. The spectral camera was unable to characterise pre-ecdysis. A least squares regression for binary classification decision boundary successfully separated 86.7% of post-moult lobsters. Achieving post-moult characterisation validated the speculative exploratory approach in developing this novel low-cost spectroscopy tool.

Understanding the interplay among organophosphorus flame-retardants (OPFRs), microplastics, and freshwater organisms is crucial for unravelling the dynamics within freshwater environments and foreseeing the potential impacts of organic pollutants and plastic contamination. For that purpose, the present research assessed the exposure impact of 10 mg L–1 flame-retardant alumin-ium diethylphosphinate (ALPI), 10 μg mg–1liver microplastics polyurethane (PU), and the combina-tion of ALPI and PU on the freshwater planarian Girardia tigrina. The exposure of G. tigrina to both ALPI and PU revealed a sequential effect, i.e., a decrease in locomotor activity, while other molecular biomarkers (oxidative stress biomarkers and metabolic response) remained unaffected. Despite this fact, it was possible to observe that the range (min-max) of responses of exposed or-ganisms were altered, in the particular case of electron transport system, cholinesterase activity, glutathione S-transferase, catalase and levels of total glutathione and proteins, showing that the energetic costs for detoxification and antioxidant capacity might be causing less energy allocated for the planarian activity. By examining the physiological, behavioural, and ecological responses of planarians to these pollutants, insights can be gained into broader ecosystem-level effects and inform strategies for mitigating environmental risks associated with OPFRs and microplastic pol-lution in freshwater environments.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori (H. pylori) infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To meet the need to develop test systems for personalized drug selection, we conducted a study of H. pylori molecular resistance in Moscow using a self-developed Sanger sequencing test platform. We validated our test system on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100%, and to levofloxacin - 93% and 92%, respectively. Then we tested our platform on 112 H. pylori -positive patients who had not previously received proton pump inhibitors (PPI) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples, and to levofloxacin in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G, to levofloxacin resistance – 261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.

This study aimed to evaluate the early-childhood comorbidities of cerebral palsy (CP) in children with low birth weight (LBW) and assess the impact of maternal bio-psychosocial factors on the risk of CP in preterm infants across varying birth weights. Data for 15,181 prematurely born infants from 2009 to 2013 and 151,810 matched controls from Taiwan's National Health Insurance Research Database were analyzed. Period prevalence of CP, and comorbidities of LBW were verified, and odds ratios (ORs) were calculated. Results confirmed that increasing prematurity and low birth weight (LBW) rates in Taiwan. LBW was associated with higher CP prevalence. Maternal age extremes (<20 and >40 years) were significant risk factors of CP in LBW infants. LBW infants showed higher risks of respiratory, circulatory, and nervous system and psycho-developmental comorbidities compared to controls. Infants with the lowest birth weights had even higher ORs for these comorbidities. However, gastrointestinal and nutritional comorbidities were less prevalent in premature infants. Maternal factors such as family income, number of hospital admissions, and length of hospital stay were significantly correlated with birth weight and subsequent complications. Each additional gestational week significantly reduced the risk of complications in premature infants. Additionally, maternal bio-psychosocial factors were associated with birth weight and related outcomes in premature infants, emphasizing the importance of addressing these factors in prenatal care and interventions.

Abstract—The static and fatigue analysis of plates with holes, made of 2D woven roving composites, is conducted. The parametrization of convex holes is proposed. Experimental results of specimens without holes and with different shapes of notches are discussed. The fatigue behaviour is considered with the use of the low cycle fatigue method. The analysis is supplemented by the numerical finite element modeling. The present work is an extension of the results discussed in the literature. The finite element modeling of plates with holes is presented in details in Ref [1-3] including also the problems of the accuracy. The experimental results and the form of specimens are shown in Ref [4]. Two parametrical description of static and fatigue behaviour of plates with holes characterizes the goal and the novelty of the paper. The fuzzy approach is employed to reduce the number of experimental data [5].

Utilizing NCEP/NCAR monthly reanalysis data alongside precipitation observations from 1936 monitoring stations across China spanning from 1966 to 2022, this study establishes a location index for the thermal low-pressure center situated over the Qinghai–Tibet Plateau. Temporal variations in the location index and summer (July) precipitation patterns in China were studied. Over the past six decades, thermal low-pressure centers have been predominantly positioned near 90°E and 32.5°N on the plateau, with their distribution extending from east to west rather than from south to north. The longitudinal and latitudinal position indices exhibit contrasting linear trends, with a positive trend observed during the 1970s and early 21st century and a negative trend in subsequent decades. Mutation analysis highlights pronounced weakening mutations occurring in 1981 and 1973, with the longitudinal index transitioning from an inter-annual cycle of approximately 6-8 years, while the latitudinal index displays quasi-cyclic oscillations of 5 and 8 and 12-14 years. Strong negative correlations are evident between the location indices and precipitation along the southeastern edge of the Qinghai–Tibet Plateau and in Southern China, contrasting with the positive correlations observed in the central-eastern plateau, northwest China, North China, and the Huang-Huai region. The influence of southerly airflow predominates over much of China east of the plateau, while northwest China experiences convergence between northerly and southerly airflow. Higher location indices correspond to weaker surface cold air masses and strengthened Western Pacific Subtropical and South Asian Highs south of the Yangtze River Basin, resulting in significantly reduced rainfall in the southern Yangtze River region and increased rainfall in northwest China.

Cellular aging is considered as one of the main factors leading to female infertility. The process called “inflammaging”, which was proposed by C. Franceschi in 2014 is characterized by chronic asymptomatic inflammation state resulting to whole body aging and age-associated diseases. In this work the inflammaging model was developed; markers expression associated with SASP (senescence associated secretory phenotype) and cell aging were verified in endometrial cells; the correlation analysis with the known inflammaging markers was done; as well as the age dynamic of markers expression in the groups of young reproductive age and late reproductive age was evaluated. For the first time, the comparative study of the expression of the key signalling molecules involved in the mechanisms of the aging was carried out: IL-6, IL-8, IL-1a, MMP3, SIRT1,6, TERF-1, CALR in endometrial cells in the age aspect and under the influence of the genotoxic stress. The SASP phenotype characterizing the phenomenon of inflammaging can be significantly expanded by the including of the studied molecules - SIRT-1, SIRT-6, TERF, CALR, that we demonstrated for the first time. These signalling molecules may be new therapeutic targets for the age-associated female reproductive system diseases treatment.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Morphological and phylogenetic (45S nrDNA+RPB1 gene) analyses of three glomoid spore-producing arbuscular mycorrhizal fungi revealed the presence of two new species be-longing to the genus Glomus in the family Glomeraceae. In the field, Glomus highlandensis sp. nov. was found in a saltmarsh of the Scottish Highlands and in maritime sand dunes of the Baltic Sea in Poland, both saline environments, while G. mongioie sp. nov. originates from the Italian Alps. Phylogenetic placement analysis using environmental sequences indicated that G. highlandensis could have likely worldwide distribution while G. mongioie seems to be a rare species in the world. The molecular and phylogenetic analysis provided important insights about the presence of ribosomal variants in Glomus, with potential negative implication in phylogeny and species recognition.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

In this paper, a 100CMM regenerative thermal oxidizer (RTO) system based on a high heating device for low-emission combustion is implemented at a volatile organic compound (VOCs) gas generation workplace. Existing RTO has a structure that repeats the inflow and discharge of VOCs gas into a cylindrical drum-type rotating disk and has excellent energy efficiency with a heat recovery rate of 95% or more. However, when used for a long time, there is a problem that rotation stops or explodes due to the discharge of pollutants due to dust and thermal expansion due to high temperature of 800℃. To overcome this, a RTO based on a high heating device was developed to reduce low-emission combustion emissions and energy use. Through 177 hours of demonstration time, the oxidation efficiency of VOCs was 98.87%; the waste heat recovery rate was reduced by 95.78%, the fuel consumption was reduced by 21.95%, and the nitrogen oxide concentration was 3.9 ppm

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

Fibroin-chitosan composites, especially those containing nanohydroxyapatite, show potential for bone tissue regeneration. The physicochemical properties of these biocomposites depend on the compatibility between their components. In this study, the intermolecular interactions of fibroin and chitosan were analyzed using a molecular dynamics approach. Two types of systems were investigated: one containing acetic acid and the other containing calcium (Ca²⁺) and hydrogen phosphate (HPO₄²⁻) ions mimicking hydroxyapatite conditions. After obtaining the optimal equilibrium structures, the distributions of several types of interactions including hydrogen bonds, ionic contacts, and hydrophobic contacts along with the structural and energetical features were examined. The calculated binding energy values for the fibroin-chitosan complexes confirm their remarkable stability. The high affinity of fibroin for chitosan can be explained by the formation of a dense network of interactions between considered biopolymers. These interactions were found to be primarily hydrogen bonds and ionic contacts involving ALA, ARG, ASN, ASP, GLN, GLU, GLY, LEU, PRO, SER, THR, TYR, and VAL residues. As it was established, the complexation of fibroin with chitosan maintains the β-sheet conformation of the peptide. β-Sheet fragments in fibroin are involved in the formation of significant amount of hydrogen bonds and ionic contacts with chitosan.

With the widespread use of new equipment such as distributed photovoltaics, distributed energy storage, electric vehicles, and distributed wind power, the control of low-voltage distribution networks (LVDNs) has become increasingly complex. Acquiring the most recent topological structure is essential for conducting accurate analysis and real-time control of LVDNs. The signal-injection-based topology identification algorithm is favored for its speed and efficiency. This study proposes a new signal-injection-based topology identification algorithm aimed at solving the issues of reduced completeness and correctness of identification caused by missing feature signal records (FSRs). By analyzing the correlations between FSRs of different positions, the algorithm employs vertical and horizontal completion methods to effectively address missing data, combined with inclusion detection algorithms, to identify the topology of LVDNs. Based on the study of actual LVDN data, the results indicate that the algorithm not only significantly improves the completeness and correctness of topology identification for LVDNs but can also increase the number of devices in operation by evaluating the status of topological equipment, further enhancing the topology identification performance.

In the process of climate change mitigation and adaptation, the focus on climate risk driven by transition innovations has received widespread attention from governments, regulators, and investors. Based on the identification of low-carbon patents through the Green and Low-carbon Technology Inventory in China, this study constructs low-carbon innovation measurements of listed firms in China from 2015 to 2021. Then, an empirical model is used to investigate the impact and mechanism of climate transition innovations on the default risk. The baseline regression model shows that low-carbon innovations can mitigate the default risk of listed firms. Moreover, our findings are supported by instrumental variable regressions that use the time costs of innovation. Finally, the mediation effect demonstrates that investor attention, total factor productivity, and technology spillovers are paths through which transition innovations can affect the default risk. This study reveals that low-carbon technological advances have a positive effect on climate transition risks.

Preschoolers with disabilities and their caregivers have been neglected in health and social service provision in most low-income countries and arguably too in low resourced areas of more affluent nations. Yet as this rapid review of published literature identifies, there are low-cost, evidence-based strategies to address their needs that can be implemented in communities by local people. Five key features of the necessary supports are examined. First the leadership functions required to create and implement the support services. Second, the family-centred, home-based support provided to caregivers and the personnel undertaking this form of support. Third, providing opportunities for peer support to flourish and encouraging the formation of advocacy groups across families. Fourth, mobilizing the support of significant groups within the community; notably traditional healers and leaders; health services and poverty alleviation initiatives. Fifth, devising ways in which preschool educational opportunities can be offered to children as a prelude to their inclusion in primary schools. The review serves a further purpose. It provides an example of how public health researchers and academics could achieve more rapid implementation of evidence-based knowledge into existing and new support services through dissemination to community practitioners.

Coarse-grained molecular dynamics simulations are employed to investigate the spatiotemporal evolution of vesicles (polymersomes) by the self-assembly of randomly distributed amphiphilic BAB triblock copolymers with hydrophilic A and hydrophobic B blocks in an aqueous solution. The vesiculation pathway consists of several intermediate structures, such as an interconnected network of copolymer aggregates, a cage of cylindrical micelles and a lamellar cage. The cage-to-vesicle transition occurs at a constant aggregation number and practically eliminates the hydrophobic interfacial area between the B block and solvent. Molecular reorganization under-lying the sequence of morphology transitions from a cage-like aggregate to a vesicle is nearly isentropic. The end-to-end distances of isolated copolymer chains in solution and those within a vesicular assembly follow log normal probability distributions. This is attributed to the pre-ponderance of folded chain configurations in which the two hydrophobic end groups of a given chain stay close to each other. However, the probability distribution of end-to-end distances is broader for chains within the vesicle as compared to that of a single chain. This is due to the swelling of the folded configurations within the hydrophobic bilayer. Increasing the hydropho-bicity of the B block reduces the vesiculation time without qualitatively altering the self-assembly pathway.

As a widely used plastic, the aging and degradation of polyethylene (PE) are inevitable problems, whether the goal is to prolong the life of PE products or address the issue of white pollution. Molecular simulation is a vital scientific tool in elucidating the mechanisms and processes of chemical reactions. To obtain the distribution and evolution process of PE's thermal oxidation products, this work employs the self-consistent charge density functional tight binding (SCC-DFTB) method to perform molecular simulations of the thermal oxidation of PE with different crystallinity and branched structures. We discovered that crystallinity does not affect the thermal oxidation mechanism of PE, but higher crystallinity makes PE more susceptible to cross-linking and carbon chain growth, reducing the degree of PE carbon chain breakage. The branched structure of PE results in differences in pore size between the carbon chains, with larger pores leading to a concentrated distribution of O2 and free radicals subsequently formed. The breakdown of PE is slowed down when free radicals are localized in low-density regions of the carbon chain. The specifics and mechanism of PE's thermal oxidation are clearly revealed in this paper, which is essential for understanding the process in-depth and for the development of anti-aging PE products.

This review provides a comprehensive and updated information on chalcones, presenting their sources, methods of identification and properties putting emphasis on applications in agricultural industry. Vast exploitation of synthetic pesticides led to the weed and pest resistance issue, causing economic loss but more importantly health risk due to pesticide overuse. Because one of the aim of the European Green Deal 2030 is the Farm to Fork strategy which targets on reducing by 50% the use of chemical pesticides by 2030, and push towards natural pesticides which are more environmentally friendly and restore natural resources, chalcones and their derivatives seem to fit perfectly. They have herbicidal, fungicidal, bactericidal and antiviral properties. Moreover, chalcones are naturally occurring substances, known for their favorable health effect for years, working on many areas. This review is complementary to the previous ones describing chalcones use in agriculture, updates them but additionally shows methods of detection.

Auxins are chemical compounds of wide interest, mostly due to their role in plant metabolism and development. Since the latter half of the XX century, synthetic auxins have been used as herbicides, presenting notable advantages, such as low toxicity in humans. As of today, extensive descriptions of syntetic and natural auxins have been made; yet studies centered on the molecular recognition process of auxins are scarce. Herein, we present a comprehensive in silico characterization of auxin receptor TIR1, using structure based methods to aid de novo design of putative ligands. In addition, we conducted binding site characterization using cosolvent molecular dynamics and enhanced sampling simulations with reference ligands. We also present a database of putative auxins and decoy compounds which can aid further studies focusing on synthetic auxin design. To the best of our knowledge, this study is the first of its kind focusing on TIR1.

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

To mitigate the adverse impacts of urban stormwater on streams, watershed managers are increasingly using low impact development and green infrastructure (LID-GI) stormwater control measures such as rain gardens—vegetated depressional areas that collect and infiltrate runoff from rooftops and driveways. Their catchment-scale performance, however, can vary widely, and few studies have investigated the cumulative performance of residential rain gardens for event runoff control in intermediate-sized (i.e., 1-10 km2) suburban catchments. We modeled three years of continuous rainfall-runoff from a 3.1 km2 catchment in Columbia, MD, USA, using the Storm Water Management Model (SWMM). Various extents of rain garden implementation at residential houses were simulated (i.e., 25%, 50%, 75%, and 100% coverage) to determine the effects on peak flow, runoff volume, and lag time. On average, treating 100% of residential rooftops in the catchment reduced peak flows by 14.3%, reduced runoff volumes by 11.4%, and increased lag times by 3.2% for the 223 rainfall events during the simulation period. Peak flow reductions were greater for smaller storm events (p<0.01). Our results show that residential rain gardens can significantly improve the runoff response of suburban catchments, and that they represent an effective and relatively low-cost option for urban watershed management and restoration.

One of the measures required by the European Green Deal to decarbonise the freight transport sector is the promotion of inland waterway transport (IWT), in particular intermodal transport in Europe. To facilitate intermodal transport on the Danube, we developed six new barge designs for the transport of 45' pallet-wide high-cube containers using a four-step approach. Our approach consisted of detailed desk research, followed by design and further analysis of the identified barge types, taking into account, for example, sight lines or stability. The container carrying capacity reaches up to 90 containers in three layers, which is double the capacity of existing standard barges on the Danube. Nevertheless, three-layer transport is hardly feasible in several cases, due to restrictions regarding sight lines and stability. We conclude that each loading condition must be evaluated separately to determine the best barge design option for each case. The study is limited by its geographical scope and the type of container used to develop the new barge designs. This could be a possible direction for further research on this topic: using other container types and/or extending the geographical scope.

African scientific research faces formidable challenges, particularly with limited access to state-of-the-art measurement instruments. The high cost associated with these devices presents a significant barrier for regional research laboratories, impeding their ability to conduct sophisticated experiments and gather precise data. This predicament not only hampers the individual laboratories but also has broader implications for the African scientific community and the advancement of knowledge in developing nations—the financial cost barrier considerably impacts the research quality of these laboratories. Reflection on technical and economical solutions needs to be quickly found to help these countries advance their research. In civil Engineering, the thermal conductivity property is the most important measurement for characterising heat transfer in construction materials. Existing devices (i.e., conductometers) in a laboratory are expensive (approximately 30,000 euros) and unavailable for some African laboratories. The study proposes a new and affordable device to evaluate thermal conductivity in construction materials. The method involves establishing a thermal flux between a heat source ( from the Joule effect provided by steel wool where a current is circulating) and a cold source (generated by ice cube) under steady-state conditions. The development of the cylindrical prototype is based on the comparative flux-meter method outlined in the measuring protocol of the ASTM E1225 standard document. Experiments were conducted on four distinct materials (polystyrene, wood, agglomerated wood, and rigid foam). The results indicate a correct correlation between the experimental values obtained from the newly developed prototype and the reference values found in the literature. For example, concerning the experimental polystyrene study, the detailed case analysis reveals a good correlation, with a deviation of only 4%. The percent error found falls within the acceptable range indicated by the standards recommendations of the ASTM E1225 standard, i.e., within 5% acceptable error.

Abstract: The Willows, belonging to the genus Salix, encompass a vast array of species and hybrids, totaling between 330 to 500 species along with approximately 200 hybrids. These plants are found across continents such as Africa, North America, Europe, and Asia, exhibiting diverse forms ranging from trees to shrubs and prostrate plants. Traditionally, Willows have been utilized in folk medicine due to their rich reservoir of biologically active compounds, with salicin being a notable example, serving as a prodrug for salicylic acid.The chemical composition of Willows is highly diverse, with 322 secondary metabolites identified thus far. These include various classes such as flavonoids (94 types encompassing flavonols, flavones, flavanones, isoflavones, flavan-3-ols like catechins and procyanidins, chalcones, dihydrochalcone, anthocyanins, and dihydroflavonols), phenolic glycosides (76), organic acids (28), non-phenolic glycosides (17), sterols, and terpenes (17), simple phenolics (13), lignans (7), as well as volatiles and fatty acids (69). This rich chemical di-versity underpins the various pharmacological activities exhibited by Willows. The pharmacological properties attributed to Willows are extensive and include analgesic, an-ti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective, and hepatoprotective effects. These properties make Willows a subject of con-siderable interest in the fields of medicine and pharmacology. In summary, Willows represent a valuable natural resource with a diverse chemical composition and a wide range of pharmacological activities. This study aimed to enhance our comprehension of the medicinal characteristics of willow bark extract, focusing on its antimicrobial properties. This investigation holds significance in validating the traditional usage of willow bark and investi-gating its potential utility in contemporary medicine.

Public housing stock, called Social Housing, in Italy developed between the 1950s and the 1980s. As of today, the first residential developments are almost nearing their end-of-life age, in need of urgent and intensive renovation. The European Commission, with the Renovation Wave, has set a goal of doubling the rate of building renovation over the next 10 years, reducing emissions, improving energy performance, and promoting decarburization. Renovation interventions, including structural, functional, energy, plant upgrading, etc., are to be preferred over integral demolition and reconstruction interventions, which have significant repercussions in terms of managerial and social discomfort. The case studies examined concern renovation interventions aimed at energy efficiency, functional adaptation of housing as well as facade restyling. The design variants analyzed were evaluated in terms of CO2e emissions, according to LCI (Life Cycle Inventory) and EPD (Environmental Product Declaration) approaches. This approach has a twofold purpose: to propose design guidelines, with low CO2e emissions, through hypotheses of variants to the case studies, and to propose, to the Economic Operators, economically advantageous bidding scenarios, in the procurement process.

The critical role of global electron density transfer (GEDT) in increasing the reaction rate of polar organic reactions has been studied within the framework of Molecular Electron Density Theory (MEDT). To this end, the series of the polar Diels-Alder (P-DA) reactions of cyclopentadiene with cyanoethylene derivatives, for which experimental kinetic data are available, have been chosen. A complete linear correlation between the computed activation Gibbs free energies and the GEDT taking place at the polar transition state structures (TSs) is found; the higher the GEDT at the TS, the lower the activation Gibbs free energy. An interacting quantum atoms (IQA) energy partitioning analysis allows establishing a complete linear correlation between the electronic stabilization of the electrophilic ethylene frameworks and the GEDT taking place at the polar TSs. This finding supports Parr’s proposal for the definition of the electrophilicity  index (J. Am. Chem. Soc., 1999, 121, 1922). The present MEDT study allows establishing the critical role of the GEDT in the acceleration of polar reactions, since the electronic stabilization of the electrophilic framework with the electron density gain is greater than the destabilization of the nucleophilic one, making a net favorable electronic contribution to the decrease of the activation energy.

In genetic conflicts, driver and killer elements achieve biased survival, replication, or transmission over sensitive and targeted elements through a wide range of molecular mechanisms, including mimicry. Driving mechanisms manifest at all organismal levels, from the biased propagation of individual genes, as demonstrated by transposable elements, to the biased transmission of genomes, as illustrated by viruses, to the biased transmission of cell lineages, as in cancer. Targeted genomes are vulnerable to molecular mimicry through the conserved motifs they use for their own signaling and regulation. Mimicking these motifs enables a selfish element to control core target processes, and can occur at the sequence, structure, or functional level. Molecular mimicry was first appreciated as an important phenomenon more than twenty years ago. Modern genomics technologies, databases, and machine learning approaches offer tremendous potential to study the distribution of molecular mimicry across genetic conflicts in nature. Here, we explore the theoretical expectations for molecular mimicry between conflicting genomes, the trends in molecular mimicry mechanisms across known genetic conflicts, and outline how new examples can be gleaned from population genomic datasets. We discuss how mimics involving short sequence-based motifs or gene duplications can evolve convergently from new mutations. Whereas, processes that involve divergent domains or fully-folded structures occur among genomes by horizontal gene transfer. These trends are largely based on a small number of organisms and should be reevaluated in a general, phylogenetically independent framework. Currently, publicly available databases can be mined for genotypes driving non-mendelian inheritance patterns, epistatic interactions, and convergent protein structures. A subset of these conflicting elements may be molecular mimics. We propose approaches for detecting genetic conflict and molecular mimicry from these datasets.

Abstract: Purpose: High-grade isthmic spondylolisthesis (HGISL) is a severe condition, associated with low-back pain (LBP) and radiculopathies. The present study is a monocentric prospective observational study investigating the clinical-radiological outcomes of a bilateral minimally invasive TLIF (bm-TLIF) for HGISL. Material and Methods: Patients who underwent bm- TLIF for HGISL at our institution, were considered for inclusion. Clinical-radiological outcomes and complications were collected. Results: Twenty-one patients (14M:7F) were included and the mean clinical follow-up (FU) time was 27(±6) months. There was a significative improvement of the mean VAS-back, VAS-legs, ODI, and SF-36 PCS scores, comparing pre- and last FU measurements. The mean pelvic tilt (p0,05). The univariate analysis showed that residual slip angle (> or  10°) may independently influence VAS-b (p

Calicioids form a research field that has encompassed ascomycetous fungi with stalked ascomata similar to those of the lichen genus Calicium. Early generic circumscriptions in calicioid lichens and fungi were mainly based on morphological and secondary chemistry information. After the introduction of molecular data, taxonomy in the group has been reconsidered. Here, based on a broad geographical sampling, Coniocybe Ach. was revised using molecular and morphological features. Three loci (ITS, LSU and rpb1) were compared to infer its phylogenetic position, and a total of 52 new sequences (14 ITS, 24 LSU and 14 rpb1) were produced. Coniocybe was revised and emended to include, apart for its type C. furfuracea, also C. brachypoda and C. confusa. In addition, a new species Coniocybe eufuracea, was described, and a key to the species of Coniocybe provided.

Rotavirus (RV) replicates within viroplasms, membrane-less electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single and double-stranded virus RNAs, and host components such as microtubules, perilipin-1 and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

The “circular bioeconomy” offers numerous opportunities for the health, cosmetic, and nutrition sectors through the potential reuse of Castanea sativa by-products. This abundant and sustainable resource provides valuable bioactive secondary metabolites with antioxidants and anti-inflammatory properties. The transformation of these by-products into high-value products for human health can contribute to sustainable economic growth and reduce the environmental impact of traditional waste disposal practices, thus creating added value from previously underutilized resources. In the present study, we investigated the antioxidant capacity, phytochemical composition and in vitro antioxidant and anti-inflammatory activity of C. sativa burrs (CSB) aqueous extract. The spectrophotometric study yielded optimal total phenolic content (TPC) values, along with significant antioxidant and anti-radical properties. The utilization of UPLC-MS-MS techniques for phytochemical investigation resulted in the identification of a total of 56 metabolites, providing confirmation of the presence of phenolic compounds in CSB. In addition, CSB significantly downregulated pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophage cells without significant cell toxicity.

The main inhibitory neurotransmitter in the mammalian brain is 4-aminobutyric acid (GABA). Phthalimide acts as a sodium channel antagonist, one of the finest targets for treating epilepsy is the sodium channel and JNK kinase activity is inhibited to treat epilepsy. a novel compound with multiple targets of action for the treatment of epilepsy also anti-oxidant activity has been designed. The compounds are designed in two series aldehydes and aniline. Docking of all the designed compounds has been done with the suitable protein GABA-AT, sodium channel, JNK protein, and anti-oxidant from protein bank. QSAR was done for constructing many linear regression models. In combination with the developed Docking and QSAR outcomes, ADMET has been performed for the active compounds. The result shows that 11 of the compounds have excellent binding energy in docking with all the receptors and also have good QSAR results and follow the ADMET. The structural understanding of human GABA-AT inhibition was obtained from molecular dynamics simulation studies for compound no. 11 at 5 nanoseconds. Synthesis and pharmacological activity also suggest that the designed compound no.11 be considered the best Novel Compound.

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection, and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley Rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and were killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis and evaluation of biological effects was performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function and cancer and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples are needed for validation.

In urban areas like Chicago, daily life extends above ground level due to prevalence of high-rise buildings where residents and commuters live and work. This study examines the variation in fine particulate matter (PM2.5) concentrations across building stories. PM2.5 levels were measured using PurpleAir sensors, installed between April 8 and May 7, 2023, on floors one, four, six, and nine of an office building in Chicago. Additionally, data were collected from a public outdoor PurpleAir sensor on the fourteenth floor of a condominium located 800 meters away. Results show that outdoor PM2.5 concentrations peak at 14 meters height, then decline by 0.11 μg/m3 per meter elevation, especially noticeable from midnight to 8 AM under stable atmospheric conditions. Indoor PM2.5 concentrations increase steadily by 0.02 μg/m3 per meter elevation, particularly during peak work hours, likely caused by greater infiltration rates at higher floors. Both outdoor and indoor concentrations peak around noon. We find that indoor and outdoor PM2.5 are positively correlated, with indoor levels consistently remaining lower than outside levels. These findings align with previous research suggesting decreasing outdoor air pollution concentrations with increasing height. The study informs decision-making by community members and policymakers regarding air pollution exposure in urban settings.

As a major coal country, China faces the issue of significant gas emissions during the coal mining process. This study aims to improve the utilization efficiency of mine gas, reduce greenhouse gas emissions, and promote the low-carbon and green transformation of the coal industry. A 10kW gas regenerative thermal oxidation (RTO) experimental system was constructed. The effects of initial methane concentration, low-temperature flue gas proportion, and operating load on combustion temperature, methane oxidation rate, high-temperature flue gas energy, and system thermal efficiency were studied. The results show that when the combustion temperature is below 600°C, the CH4 combustion reaction cannot proceed effectively, and the system temperature continuously decreases and cannot be maintained stable. The experiment determines the stable operating methane concentration range of RTO. In this experimental system, the lower limit of the initial methane concentration is 0.28%, corresponding to an 86% methane oxidation rate. As the initial methane concentration decreases, the combustion temperature also decreases, and the methane oxidation rate follows suit. The higher the low-temperature flue gas proportion, the higher the combustion temperature, and the system thermal efficiency and output heat decrease with the increase of the low-temperature flue gas proportion. This experiment explores multiple factors affecting regenerative thermal oxidation, providing an basis for ensuring the safe and stable operation of the system and optimization. Improving the thermal insulation and heat exchange performance of the storage body can expand the lower limit of the initial methane concentration, thereby increasing the stability and thermal efficiency of the system.

Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines, and 3D tumor models. To address this goal, a well characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G > T (p.(Gly12Val)) was used. Fluorescently labelled tumor cells were injected into the perivitelline space of 2 days post fertilization zebrafish embryos. At 1 day post-injection xenografts were as-sessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib, and trametinib + luminespib. Subsequently xenografts were euthanized and analysed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n=84) in vivo and with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.

To reduce the redundant counting of TDC in high-speed applications and thus reduce power consumption, a TDC architecture is proposed to quantify the difference between two adjacent rows of pixel signals. This structure can remove the identical part between two rows of pixel signals by adjusting the start and stop signal of the TDC, which will reduce the number of flipping of D flip-flops in the TDC. In the 110nm CMOS process, simulation results show that this design achieves an effective number of bits (ENOB) of 4.72 bits and a Figure of Merit (FoM) of 104.7 fJ/step - 162.3 fJ/step with a power consumption ranging from 60 µW to 93 µW. Compared with traditional counting methods, the proposed TDC can reduce counting power consumption by 30%.

Live video streaming has become one of the main multimedia trends in networks in recent years. Providing Quality of Service (QoS) during live transmissions becomes a challenge due to the stringent requirements for low latency and minimal interruptions. This scenario has led to a high dependence on cloud services, implying a widespread usage of Internet connections, which constrains contexts where an Internet connection is not available. Thus, alternatives such as Mobile Ad Hoc Networks (MANETs) emerge as potential communication techniques. These networks operate autonomously with mobile devices serving as nodes, without the need for coordinating centralized components. However, these characteristics lead to challenges to live-video streaming, such as dynamic node topologies or periods of disconnection. Considering these constraints, this paper investigates the application of Artificial Intelligence (AI)-based classification techniques to provide adaptive streaming in MANETs. For this, a software-driven architecture is proposed to route stream in offline MANETs, predicting the stability of individual links and compressing video frames accordingly. The proposal has been implemented and assessed in a laboratory context, analyzing the model performance and QoS metrics. As a result, the model is implemented in a decision forest algorithm, which provides 95.9% of accuracy. Also, obtained latency values become assumable for video streaming, manifesting a reliable response for routing and node movements.

Motivated by experimental success in designing linear amphiphilic copolymers with selective demicellization capabilities through head-to-tail depolymerization triggered by specific stimuli, we advanced the design paradigm by increasing the number of triggering groups on the copolymer chain through architectural modifications. Utilizing molecular dynamics simulations, we explored the demicellization and cargo release dynamics of linear and miktoarm copolymers, featuring one, two and three hydrophobic block or branches, each capable for head-to-tail depolymerization. Our findings revealed that, under stoichiometric trigger molecule concentrations, miktoarms with three branches exhibited consistently faster depolymerization rates than those with two branches and linear copolymers. Conversely, at constant trigger molecule concentrations, the depolymerization rates of copolymers exhibited more complex behavior influenced by two opposing factors: the excess of trigger molecules, which increased with a decrease in the number of hydrophobic branches or blocks, and simultaneous head-to-tail depolymerization, which intensified with an increasing number of branches. Our study elucidates the intricate interplay between copolymer architecture, trigger molecule concentrations, and depolymerization dynamics, providing valuable insights for the rational design of amphiphilic copolymers with tunable demicellization and cargo release properties.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular docking were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating noncompetitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. Simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

This study explores the significance of active suspension systems for vehicles with lower chassis compared to conventional ones, aiming at the development of future automobiles. Conventional linear MR (Magneto-Rheological) dampers were found inadequate in ensuring sufficient vibration control because the vehicle's chassis becomes lowered in the unmanned vehicles or purposed based vehicles. As an alternative, a rotary type of MR damper is proposed in this work. The proposed damper is designed based on pre-specified design parameters through mathematical modeling and magnetic field analyses. Subsequently, a prototype of the rotary MR damper identical to the design is fabricated, and effectiveness is shown through experimental investigations. In configuring the experiments, a proportional-integral (PI) controller is employed for current control to reduce the response time of the damper. The results presented in this work provides useful guidelines to develop a new type of MR damper applicable to various types of future vehicles’ suspension systems with low distance from the tire to the body floor.