In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

Researchers are exploring solutions to meet the growing demand for protein due to the expected increase in global population by 2050. Interest in alternative protein sources like insects has risen, driven by concerns about environmental impact and the need for sustainable food production. This study aimed to develop and evaluate the physicochemical properties of soy protein-based burger enriched with insect protein from Alphitobius diaperinus. Three formulations were developed: a control (B0), and burgers with 5% (B5) and 10% (B10) insect protein - Whole Buffalo Powder (WBP). Results showed that adding insect protein decreased the burger analogue's pH. There was observed a clear trend of increasing total lipids and SFA, and decreasing MUFA and PUFA, as the WBP concentration increases from 0% to 10%. No significant differences with increasing WBP concentration in the protein content of the burger analogue, as well as the cooking yield, were noted. The WBP addition had a notable effect on the color change, especially decrease in brightness (L*). It was shown that as the WBP concentration increased, there were no significant differences in the texture profile of the burger analogues. The formulation with 5% WBP concentration was the most acceptable in sensory analysis.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light 22 Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to low micrometric sizes. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. More in detail, in the dimer formation achieved by molecular self-docking, two distinct poses were observed, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

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.

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the amyloid precursor protein (APP) gene. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSS) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed the higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92–169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. Examination of tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some of the neuronal ceroid lipofuscinosis (NCL) diseases. The also dog exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband’s DNA revealed a homozygous C to T substitution that altered the intron 3 – exon 4 splice site of CLN6. Other mutations in CLN6 cause NCL diseases in humans and animals including dogs. CLN6 protein was undetectable with immunolabeling in the tissues of the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the disorder in this dog is classified as an NCL resulting from the absence of CLN6 protein. Screening the dog’s genome for a panel of breed-specific polymorphisms indicated that its ancestry included numerous breeds, with no single breed predominating. This suggests that the CLN6 disease variant is likely to be present in other mixed breed dogs and at least some of the ancestral breeds.

Thermodynamics of protein-ligand interactions seems to be associated to a narrow range of Gibbs Free Energy. As a consequence, a linear enthalpy-entropy relationship showing an apparent Enthalpy-Entropy compensation (EEC) is frequently observed associated to the study of protein-ligand interactions. This EEC affects negatively the design and discovery of new and more efficient drugs capable of binding protein-targets with a higher affinity. Originally attributed to experimental errors, compensation between H and TS values is a real observable fact, although its molecular origin has remained obscure and controversial. Herein we show the results of a data search of G values of 2558 protein-ligand interactions and 3025 “in vivo” ligand concentrations from the Protein Data Bank bind Database and the Metabolome Data Base (2020). These results, together with the mechano-statistical interpretation of the thermodynamic properties leads to the conclusion that the EEC has no basis in statistical thermodynamics. It can be plausibly explained as a consequence of the narrow range of G associated to protein-ligand interactions. The Gaussian distribution of the G values matches very well with that of ligands. These results suggest the hypothesis that the set of G values for the protein-ligand interactions is the result of the evolution of proteins. The conformation versatility of present proteins and the exchange of thousands (even millions) of minute amounts of energy with the environment may have functioned as a homeostatic mechanism to make G of proteins adaptive to changes in availability of ligands, and therefore achieve the maximum regulatory capacity of the protein function. Finally, a plausible strategy to avoid the EEC is suggested.

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.

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.

Adeno-associated viruses (AAVs) have been used for liver gene therapy. Hemgenix and Roctavian are AAV-based treatments for hemophilia B and A, respectively. They cost $3 million and $2.8 million per dose, respectively. While AAV vectors may eventually be cheaper to mass produce, a bacteria-based DNA delivery system might be much cheaper for patients. Also, “bactofection” would allow for the delivery of much larger DNA packages. Such a bacterial system may now be possible, and a prototype for the liver could possibly be developed immediately.

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

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. Psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

In this work, we explore the intrinsic disorder status of the three members of the synuclein family of proteins - α-, β-, and γ-synucleins. We also analyzed the peculiarities of the amino acid sequences and modeled 3D structures of the human synuclein family members to find potential effects of pathological mutations. Furthermore, we conducted a comparative sequence-based analysis of the synuclein proteins from various evolutionary distant species and evaluated their levels of intrinsic disorder using a set of commonly used bioinformatics tools. Next, we conducted a detailed functional disorder analysis of the proteins in the interactomes of the human synuclein family members using various web-based disorder analysis and prediction tools, such as RIDAO, D2P2 and FuzDrop. We identify that the interactome of human α-synuclein has relatively higher levels of intrinsic disorder, as compared to the interactomes of human β- and γ- synucleins. These observations highlight the critical importance of intrinsic disorder of human α-synuclein and its interactors in neuronal processes as compared to other proteins of the synuclein family.

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.

As the world attempts to decarbonise the food industry and limit greenhouse gas (GHG) emissions, plant-based meat analogues (PBMAs) have emerged as a sustainable alternative to traditional meat. This study implemented a life cycle assessment (LCA) to rigorously compare the environmental impacts of a beef burger (BB), produced with British beef, against a meat analogue (MA) equivalent with a publicly available recipe. For the LCA, a cradle-to-fork system boundary was utilised, alongside a functional unit of a single 100 g burger patty. Results from the LCA revealed that the BB patty had more than double the total environmental impact than the MA equivalent, as well as possessing a global warming impact that was 62% higher. A simple extrapolation illustrated that if the UK population switched from beef to meat analogue patties, 3 million tonnes of CO2e could be saved annually, corresponding to 0.74% of the country’s yearly territorial GHG emissions. Scenario analyses displayed how the environmental impact of the MA patty remained stable regardless of changes in exportation, ingredient origin or soy protein sourcing. Moreover, sensitivity analysis conducted with an alternative characterisation method corroborated initial findings, whilst uncertainty analysis ensured that nearly all conclusions generated from the original comparison were robust. Future studies should conduct peer-reviewed LCAs on PBMA patties with commercial recipes based on other plant-based proteins, as well as fully understanding any potential health implications of long-term PBMA consumption.

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.

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

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.

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.

Both grape pomace and whey are waste products from the food industry that are rich in valuable ingredients. The utilisation of these two by-products is becoming increasingly possible as consumer awareness of upcycling increases. The biological activities of grape pomace extract (GPE) are diverse and depend on its bioavailability, which is influenced by processes in the digestive system. In this work, goat whey protein (GW) was used as the primary coating to protect the phenolic compounds of GPE during the spray drying process. In addition, trehalose (T), sucrose (S), xylose (X) and maltodextrin (MD) were added to the goat whey proteins as co-coatings and protein stabilisers. All spray drying experiments resulted in microcapsules (MC) with high encapsulation efficiency (77.6—95.5%) and yield (91.5—99.0%) and almost 100% recovery of phenolic compounds during the release test. For o-coumaric acid, the GW-coated microcapsules (MC) showed a bioavailability index of up to 731.23%. A semi-crystalline structure and hydrophilicity are characteristics of the MC coated with 10% T, S, X or 5% MD. GW alone or in combination with T, S, MD or X has proven to be a promising carrier for polyphenols from grape pomace extract and ensures good bioavailability of these natural antioxidants.

The severe and complex COVID-19 symptoms, often needing hospital care, occur suddenly, late in the virus replication stage of SARS-CoV-2 infection. Hospitalised patients have tissue damage due to micro-clots at multiple sites. Could long-covid, also clinically variable, be a milder form caused by “nano-clots”, too small to cause detectable tissue damage? The timing and suddenness of the onset of serious disease needs an explanation. A paper reported on the first 20 children needing urgent hospital care. No child had any symptoms prior to suddenly becoming seriously ill, only one had a positive PCR test but all had positive SARS-CoV-2 antibody test. That finding indicated to me that this onset occurred at the moment of sero-conversion. An emerging viral moiety, the virion-IgG-antibody complex, has concentrations rapidly increasing, then decreasing. It is known that influenza-IgG-antibody-complex consists of many virions bound together by the antibody. It seems a reasonable step to propose that SARS-2, being a large virus and having many spike proteins, can form larger clumps of virus-IgG-antibody complexes than with influenza, the former being sufficiently large to initiate micro-clots. Therefore, my hypotheses is that the SARS-CoV-2 virion-antibody complex initiates micro-clot formation. Either before or after sero-conversion, the complex will be at too low a concentration to initiate micro-clots. To be useful, a hypothesis should be testable, provide explanations and give predictions. My presentation will give examples. I like the way that several apparently separate pieces of a jig-saw puzzle have come together to form a single picture. [I suggest that the reader scrolls down to the addenda [10,11 & 12] before reading the ICAR Poster]

Proteins have the ability to adsorb on the surface of materials, such as soft contact lenses (SCLs), and can affect the hydrophobicity, roughness and surface properties of the contact lenses (CLs), which, in turn, can influence the friction between the lenses and the ocular surface. Excessive friction between contact lenses and the ocular surface can lead to discomfort for the wearer and may cause irritation or inflammation of the cornea, better known as corneal ulcers (keratitis). Bovine serum albumin (BSA) is often used as a standard protein in biocompatibility testing of materials, including contact lenses. One standard commercial contact lenses was tested under lubricated conditions to access the coefficient of friction (CoF), being the contact lubricated with a tear like fluid (TLF) solution containing six different concentrations of BSA. In all cases, a good linearity of the results of the friction force was verified, so the first friction law can be applied to determine the value of the coefficient of friction. It was found that friction increases with increasing protein concentration.

Enteroviruses (EV) are important pathogens causing human disease with various clinical manifestations. To date, treatment of enteroviral infections is mainly supportive since no vaccination or antiviral drugs are approved for their prevention or treatment. Here, we describe the antiviral properties and mechanisms of action of leucoverdazyls - novel heterocyclic compounds with antioxidant potential. The lead compound, 1a, demonstrated low cytotoxicity along with high antioxidant and virus-inhibiting activity. A viral strain resistant to 1a was selected, and the development of resistance was shown to be accompanied by mutation of virus-specific non-structural protein 2C. This resistant virus had lower fitness when grown in cell culture. Taken together, our results demonstrate high antiviral potential of leucoverdazyls as novel inhibitors of enterovirus replication and support previous evidence of an important role of 2C proteins in EV replication.

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.

Due to the vast conformational space proteins can adopt, accurate and efficient prediction of protein structure remains still a challenging task, coupled with the intricacies of interatomic interactions and the limitations of current computational models in effectively navigating this complex molecular landscape. Additionally, the lack of comprehensive experimental data for all protein structures further exacerbates the difficulty in reliable machine learning-based prediction of the three-dimensional conformations of the proteios building block of life. Geometrically, Cartesian coordinate system (CCS, X, Y and Z) and spherical coordinate system (SCS, ρ, θ and φ) are two interconvertible coordinate systems, and are like two sides of one coin. Since the beginning of Protein Data Bank (PDB) in 1971, CCS has been the default approach to specify atomic positions with X, Y and Z in PDB. In this manuscript, therefore, I present a novel method for the reversible spherical geometric conversion of protein backbone structure coordinate matrices to three independent vectors: ρ, θ and φ. This reversible conversion facilitates lossless extraction of essential structural features from protein backbone structural data, enabling the development of advanced novel algorithms for protein structure prediction in future. In short, this inter-atomic SCS approach offers a comprehensive yet efficient means of representing protein backbone geometry, leveraging spherical coordinates to capture spatial relationships in a compact and intuitive inter-atomic manner, and to provide a robust framework for reversible feature extraction for the ongoing efforts in advancing the field of protein structure prediction, the holy grail of computational structural biology.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Yeast two-hybrid approaches, which are based on fusion proteins that must co-localise to the nucleus to reconstitute the transcriptional activity of GAL4 have greatly contributed to understand the nitrogen interaction network of cyanobacteria, whose main hubs are the trimeric PII and the monomeric PipX regulators. The bacterial two-hybrid system, based on the reconstitution in the E. coli cytoplasm of the adenylate cyclase of Bordetella pertussis, should provide a relatively faster and presumably more physiological assay for cyanobacterial proteins than the yeast system. Here we use the bacterial two-hybrid system to gain additional insights into the cyanobacterial PipX interaction network while simultaneously assessing the advantages and limitations of the two most popular two-hybrid systems. Comprehensive mutational analysis of PipX and bacterial two-hybrid assays were performed to compare outcomes between yeast and bacterial systems. We detected interactions previously recorded in the yeast two-hybrid system as negative as well as a “false positive”, the self-interaction of PipX, which is rather an indirect interaction dependent on PII homologs from the E. coli host, a result confirmed by Western analysis with relevant PipX variants. This is, to our knowledge, the first report of the molecular basis of a false positive in the bacterial two-hybrid system.

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.

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

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS), arise due to numerous causes like protein accumulation and autoimmunity, characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform a critical role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. MiRNA participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative diseases (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlighted miRNA as therapy.

Variable and sometimes contrasting effects of using artificial rhizobium inocula to increase grain legume performance have been reported. The objectives of this systematic review and meta-analysis were therefore to (i) estimate the overall effect of rhizobium inocula on grain yield and protein content and (ii) identify potential confounding factors that explain the observed variation. A web of Science database literature search was carried out in 2016. Data from all field experiments, greenhouse and pot experiments that compared grain yields and protein contents in Rhizobium/Bradyrhizobium-inoculated with non-inoculated control crops were extracted and analyzed using previously described unweighted and weighted meta-analysis protocols. GRADE assessments of the strength of evidence of results from the weighted meta-analyses were carried which included an assessment of the risk of publication bias. Results: For unweighted meta-analyses we identified eligible data in 236 and 36 studies for grain yield and protein content respectively. For weighted meta-analyses we identified eligible data in 92 and 8 studies for grain yield and protein content respectively. Rhizobium inoculation was found to (i) significantly increase grain yield in both the unweighted (mean percent difference: 41%, 95%CI 36,46, p<0.0001) and weighted meta-analysis (Standardized mean difference: 1.56, 95%CI 1.26,1.87, p<0.0001) and (ii) significantly increase protein content in the unweighted meta-analysis (mean percent difference: 11%, 95%CI 5,18, p<0.0001), but not the weighed meta-analyses which only detected a trend (0.1>p>0.05) towards higher protein content in inoculated grain legume crops. Multi-level model-based weighted meta-analyses suggest that the (i) type of experiment, (ii) type of fertilizer used in experiments, (iii) grain legume type/species and (iv) the country in which experiments were carried out, were confounding factors. The main limitation of the evidence is that a large number of publications did not report measures of variation and could therefore not be included in the more scientifically sound weighted meta-analyses. However based on the large evidence-base available for grain yield it can be concluded that overall Bradyrhizobium/Rhizobium seed inoculation results can increase grain yield by ~40% compared with non-inoculated grain legume crops.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

Succinic semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme involved in the catabolism of the neurotransmitter γ-amino butyric acid. Pathogenic variants in the gene encoding this enzyme cause SSADH deficiency, a developmental disease manifesting as hypotonia, autism and epilepsy. SSADH deficiency patients usually have family-specific gene variants. Here, we describe a family exhibiting four different SSADH variants, Val90Ala, Cys93Phe, and His180Tyr/Asn255Asp (a double variant). We provide a structural and functional characterization of these variants and show that Cys93Phe and Asn255Asp are pathogenic variants that affect the stability of the SSADH protein. Due to impairment of the cofactor NAD+ binding, these variants show a highly reduced enzyme activity. However, Val90Ala and His180Tyr exhibit normal activity and expression. The His180Tyr/Asn255Asp variant exhibits a highly reduced activity as a recombinant species, is inactive and shows a very low expression in eukaryotic cells. A treatment with substances that support protein folding by either increasing chaperone protein expression or by chemical means was not capable of increasing the expression of the pathogenic variants of the SSADH deficiency patient. However, stabilization of the folding of pathogenic SSADH variants by other substances may provide a treatment option for this disease.

Multiple myeloma (MM) accounts for about 10 to 15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60-minute workouts 3 times a week was conducted. Body mass and composition and the levels of: vitamin D, calcium and phosphorus, beta2-microglobulin and albumin were examined before and after completion of training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN) and Tartrate-resistant acid phos-phatase 5b (TRACP 5b). There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumines was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p=0.001 and p=0.022, re-spectively). The change in the concentration of this vitamin negatively correlated with the con-centration of TRACP 5b (r=-0.413, p=0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p=0.026, time vs. group: p=0.033) and TRACP 5b (time: p

The PAX8/PPARγ rearrangement, producing the PAX8–PPARγ fusion protein (PPFP), is thought to play an essential role in the oncogenesis of thyroid follicular tumors. To identify PPFP-targeted drug candidates and establish an early standard of care for thyroid tumors, we performed ensemble docking-based compound screening. Specifically, we investigated which pocket structure should be adopted to search for a promising ligand compound for the PPFP; the position of the ligand binding pocket on the PPARγ side of the PPFP is common to that of PPARγ; however, the shape is slightly different between them due to environmental factors. We developed a method for selecting a PPFP structure with a relevant pocket and high prediction accuracy for ligand binding. This method was validated using PPARγ, whose structure and activity values are known for many compounds. Then, we performed docking calculations to PPFP for 97 drug or drug-like compounds with a thiazolidine backbone, which is one of the characteristics of ligands that bind well to PPARγ, registered in the DrugBank database. Furthermore, the binding affinities of promising ligand candidates were estimated more reliably using the molecular mechanics-Poisson–Boltzmann surface area method. Thus, we propose promising drug candidates for the PPFP with a thiazolidine backbone.

The expanding global population has increased the demand for sustainable protein sources, and microbial protein (MP) has emerged as a promising alternative. However, conventional carbon (glucose) and nitrogen (ammonia, urea) sources needed for MP production pose environmental and economic issues. This study aims to produce protein using lignocellulosic biomass (LCB) as a carbon source and the nitrogen fixation ability of Klebsiella oxytoca M5A1 as a nitrogen source. The study investigates the pretreatment of LCB (switchgrass), enzymatic hydrolysis, protein quantification, and high-performance liquid chromatography system (HPLC) analysis to track glucose utilization and organic acid production. K. oxytoca M5A1 harnessed free nitrogen from the atmosphere through nitrogen fixation and used abundant, cheap glucose from LCB to produce MP and organic acids as by-products. Protein production occurred in two phases: first within the initial 8 hours and secondly, within the last 16 hours. The highest protein concentration was at 40 hours, with approximately 68.3% protein content. HPLC analysis revealed a dynamic profile of glucose utilization and organic acids (Lactic acid, Propionic acid, Acetic acid, and Succinic acid). K. oxytoca M5A1 exhibited an early high rate of glucose consumption, and conversion to organic acids that were later used for second-phase protein production. The acids profile revealed intra-conversion from one acid to another via metabolic pathways (glycolysis and tricarboxylic acid cycle). Overall, leveraging LCB and the nitrogen-fixing ability of K. oxytoca M5A1 for MP production offers an eco-friendly and cost-effective alternative to traditional protein sources, contributing to a sustainable circular economy.

Recent advancements in artificial intelligence (AI) and deep learning have revolutionized the field of protein engineering, particularly in the area of de novo protein design. This review article explores the impact of AI-driven approaches on protein design, with a specific focus on the role of structure prediction neural networks, such as AlphaFold and RoseTTAFold. The article discusses the paradigm shift brought about by these networks, which have enabled the design of proteins with unique structures and functions that are not found in nature. The review covers various aspects of AI-driven protein design, including the use of protein language models to harness evolutionary information, the development of de novo protein design workflows utilizing deep learning, and the application of generative models like RFdiffusion and RoseTTAFold All-Atom. The article also highlights the successes and applications of AI-driven protein design across diverse domains, such as enzyme engineering, antibody design, and vaccine development. Additionally, the review identifies current challenges and future directions in the field, emphasizing the need to address limitations in modeling conformational dynamics and designing proteins for in vivo functionality. The article concludes by underscoring the potential of AI-driven protein design to transform various aspects of science and technology, while also acknowledging the importance of interdisciplinary collaboration and the development of robust pipelines for the validation and optimization of designed proteins. Overall, this comprehensive review serves as a valuable resource for researchers and practitioners interested in understanding the current state and future prospects of AI-driven protein design.

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.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the missense mutations found in the 2,535 proteins involved in Mendelian rare diseases (MRD), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRD show different mutation site distributions at different three-dimensional protein depths. We then predicted the depth-dependent effects of mutations for the 20,248 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance of inactivated SARS-COV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-COV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprising of UV-inactivated SARS CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (Limit of Detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a twenty amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates.

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.

Sea cucumber peptides are small molecular peptides with biological function obtained from fresh sea cucumber as feedstock, which were hydrolyzed by protease, separated ,and purified. As the main product of sea cucumber refinement, it more accurately expresses the nutritional effect of sea cucumber and has a wide range of potential applications. It has been demonstrated that sea cucumber has a certain value-added effect on bone mineral density regulation, but the differences in bone mineral density regulation of extracts from different parts of sea cucumber and the techniques contributing to the efficient isolation of bone sea cucumber peptides have not been reported. Firstly, the aim of this study was to reveal the differences in osteogenic activities of enzymatic peptides from three major parts of sea cucumber: the body wall, the egg protein, and the intestinal protein. Then, the bone-enhancing sea cucumber peptides were isolated based on the characteristics of the dif-ferences in molecular weight distribution, hydrophilicity, and ionisation degree of sea cucumber, and to explore the possible mechanisms of their action. The findings indicated that sea cucumber peptides extracted from three distinct sites exhibited a dose-dependent enhancement of osteoblast proliferation and differentiation. Upon evaluating the three methods of sea cucumber peptide separation based on molecular weight distribution, hydrophilicity, and ionization, it was observed that the fraction isolated by hydrophobicity and

Theoretical and experimental approaches have been applied to study the polymer physics under-lying compaction of DNA in the bacterial nucleoid. Knowledge of the compaction mechanism is necessary to obtain a mechanistic understanding of the process of segregation of replicating chromosome arms (replichores) during the cell cycle. In the first part of this review light microscope observations are discussed that have demonstrated that the nucleoid has a lower refractive index and thus a lower density than the cytoplasm. A polymer-physical explanation for this phenomenon was given by the theory of Theo Odijk pro-posed in 1998. By assuming a phase separation between nucleoid and cytoplasm and by imposing equality of osmotic pressure and chemical potential between the two phases, a minimal energy situation is obtained in which soluble proteins are depleted from the nucleoid, thus explaining its lower density. The theory is compared with recent views for DNA compaction that are based on mere exclusion of polyribosomes from the nucleoid or on the transcriptional activity of the cell. These new views raise the question of whether they can still explain the lower refractive index or density of the nucleoid. In the second part of this review the question is discussed how DNA segregation occurs in Esche-richia coli, in the absence of the so-called active ParABS system, present in the majority of bacteria. How is entanglement prevented of nascent chromosome arms, generated at the origin in the pa-rental network of the E. coli nucleoid? The observations of the groups of Sherratt and Hansen in 2006, that the four nascent chromosome arms synthesized in the initial replication bubble, segre-gate to opposite halves of the sister nucleoids implies that extensive intermingling of daughter strands does not occur. Based on the hypothesis that leading and lagging replichores synthesized in the replication bubble, fold into micro-domains that do not intermingle, a passive "four-excluding-arms model" for segregation is proposed. This model implies that the key for seg-regation already lies in the structure of the replication bubble at the very start of DNA replication; it explains the different patterns of chromosome arms as well as the segregation distances between replicated loci as experimentally observed.

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.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p<0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p<0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

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.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.

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.

Exposure to ionizing radiation, accidental or intentional, may lead to delayed effects of acute radiation exposure (DEARE) that manifest as injury to organ systems including kidney, heart, and brain. This study examines the role of activated protein C (APC), a known mitigator of radiation-induced early toxicity, in long-term plasma metabolite and lipid panels that may be associated with DEARE. Male and female cohorts of C57BL/6N wild-type and APCHi transgenic mice were exposed to 9.5 Gy γ-rays with their hind-legs shielded to allow long-term survival that is necessary to monitor DEARE, and plasma was collected at 6 months for LC-MS based metabolomics and lipidomics. We observed significant dyslipidemia, indicative of inflammatory phenotype, upon radiation exposure. Additionally, observance of several other metabolic dysregulations was suggestive of gut damage, perturbations in TCA and urea cycles, and arginine metabolism. We also observed gender and genotype modulated metabolic perturbations post radiation exposure. The APCHi mice showed near normal abundance for several lipids. Moreover, restoration of plasma levels of some metabolites including amino acids, citric acid, and hypoxanthine in APCHi mice are indicative of APC-mediated protection from radiation injuries. With the help of these findings the role of APC in plasma molecular events after acute -radiation exposure in a gender-specific manner can be established for the first time.

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

Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs—e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly-large local and global footprints within and across cells, through mechanisms involving electrophile signaling. Burgeoning efforts are being put into profiling mt-REMs’ potential protein-targets and phenotypic mapping of their multifaceted inflammatory behaviors. Yet, precision indexing of mt-REMs’ first-responders with spatiotemporal intelligence and locale-specific function assignments remains elusive. Highlighting the latest advances and overarching challenges, this perspective aims to stimulate thoughts and spur interdisciplinary innovations to address these unmet chemical-biotechnological needs at therapeutic immuno-signaling frontiers.

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

Cucurbitacin phytonematicides consistently suppress population densities of plant nematodes, but have no effect against bacteria, fungi and insects. This study investigates the mechanism through which cucurbitacin phytonematicides consistently exert nematicidal properties on nematodes. Post 72-h exposure of second-stage juveniles (J2) of Meloidogyne enterolobii to geometric concentration of Nemafric-BL phytonematicide, J2 total proteins were measured using TruspecCHNS Macro. Total proteins versus phytonematicide exhibited a negative quadratic relation (R² = 0.97), with the minimum total proteins achieved at x = 4.9% phytonematicide. Beyond the minimum, total proteins increased gradually, depicting the existence of both isoprenylation (breakdown) and farnesylation (biosynthesis) of total proteins. In conclusion, cucurbitacins and nematode cuticles are both chemically structured, which provides the mechanism through which the test chemicals consistently decrease population densities of plant nematodes.

With the rapid evolution of SARS-CoV-2, the emergence of new strains is an intriguing question. This paper presents an evolutionary theory to analyze the mutations of the virus and identify the conditions that lead to the generation of new strains. We represent the virus variants using a 4-letter sequence based on amino acid mutations on the spike protein and employ an n-distance algorithm to derive a variant phylogenetic tree. We show that the theoretically-derived tree aligns with experimental data on virus evolution. Additionally, we propose an A-X model, utilizing the set of existing mutation sites (A) and a set of randomly generated sites (X), to calculate the emergence of new strains. Our findings demonstrate that a sufficient number of random iterations can predict the generation of new macro-lineages when the number of sites in X is large enough. These results provide a crucial theoretical basis for understanding the evolution of SARS-CoV-2.

The conserved cyanobacterial protein PipX is part of a complex interaction network with regulators involved in essential processes that include metabolic homeostasis or ribosome assembly. Because PipX interactions depend on the relative levels of their different partners and of the effector molecules binding to them, in vivo studies are required to understand the physiological significance and contribution of environmental factors to regulation of PipX complexes. Here we have used the NanoBiT complementation system to analyse regulation of complex formation in Synechococcus elongatus between PipX and each of its two best characterized partners, PII and NtcA. Our results confirm previous in vitro analysis on regulation of PipX-PII and PipX-NtcA complexes by 2-oxoglutarate and on regulation of PipX-PII by the ATP/ADP ratio, showing the disruption of PipX-NtcA complexes by increased levels of ADP-bound PII in Synechococcus elongatus. The demonstration of a positive role of PII on PipX-NtcA complexes under the initial response to nitrogen starvation or the impact of a PipX point mutation on the activity of PipX-PII and PipX-NtcA reporters are further indications of the sensitivity of the system. This study reveals additional regulatory complexities in the PipX interaction network, opening the way to future research in cyanobacteria.

Analysis of liquid biopsy samples can reveal a wealth of molecular as well as cellular entities circulating in various body fluids. These entities include circulating tumor cells, circulating cell-free and tumor DNA, RNA, and proteins. Detection and characterization of this genetic and proteomic material can provide crucial information on tumor characteristics, including its heterogeneity, biology, tumor progression, staging, associated gene mutations and the course of therapy. The increased use of liquid biopsy in clinical oncology offers in non-invasive manner easier tumor sampling and continuous monitoring of the disease evolution through repetitive sampling from cancer patients. The continuous monitoring offered by this method is highly relevant to the assessment of a given therapeutic regime and early detection of markers associated with possible drug resistance, which may develop in the course of the therapy. The use of proteomic approaches, including mass spectrometry-based proteomics for the analysis of biofluids extends for over three decades, yet only in the last few years such methods have found their way to clinical oncology. The non-invasive nature of liquid biopsy and the simple procedures for sample collection made this approach far more attractive than the traditional and well-established tissue biopsy. Such preference becomes more practical in the analysis of solid tumors, particularly in pediatric population. In this review we discuss some works on the emerging role of liquid biopsy analyses in clinical oncology, and how such use allows a better understanding of diagnosis, prognosis, disease evolution and response to therapy of various forms of cancer. We also discuss the role of MS-based methods in the characterization of post-translational modifications of proteins circulating in liquid biopsies.

Few studies have examined the dietary protein intake and sources in combination with the longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were included in the analysis. The relative and absolute amounts of dietary protein intake were calculated through a 24-hour dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake is associated with a slower reduction in the total hippocampus volume (THV, β: -0.02524, P<0.05), left hippocampus volume (LHV, β: -0.02435, P<0.01) and right hippocampus volume (RHV, β: -0.02544, P<0.05).Higher intake of animal protein relative to plant protein is linked to a lower atrophy rate in THV (β: -0.01249, P<0.05) and LHV (β: -0.01173, P<0.05) and RHV (β: -0.01193, P<0.05). Individuals with higher intake of seafood exhibit lower longitudinal rate of change in HV compared to those with no consume (THV, β: -0.004514; P<0.05; RHV, β: -0.005527, P<0.05). In subgroup and sensitivity analyses, there was not a significantly alteration. A moderate increase in the intake and proportion of animal protein in the diet, especially from seafood, is associated with a lower longitudinal change rate in hippocampus volume.

Dengue is one the most significant mosquito-borne viral diseases globally, with its prevalence extending across tropical and subtropical regions, exerting a considerable financial strain on health systems. Despite decades of research leading to the development of a vaccine implemented in endemic countries, its usage remains restricted to a fraction of the population at risk of contracting dengue. Due to these limitations, there is a growing focus on research aimed at unraveling the cellular mechanisms crucial for Dengue virus (DENV) infection to pinpoint potential host targets. Multiple studies propose a pivotal role of cytoskeletal remodeling in DENV infection. Specifically, DENV alters the organization of actin to facilitate viral entry, replication, and release. In this study, we investigated the involvement of the protein c-Abl, a kinase crucial in actin dynamics, in the context of DENV infection. Our findings suggest that either silencing or pharmacological inhibition of the kinase c-Abl leads to accumulation of dengue ENV protein in vitro, associated with actin remodeling. These results illuminate cellular mechanisms that could serve as potential therapeutic alternatives for dengue management.

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.

Proteomic analysis of purified rabies virus (RABV) revealed 47 entrapped host proteins within viral particles. Out of these, 11 proteins were highly disordered. Our study was particularly focused on five of the RABV-entrapped mouse proteins with the highest levels of disorder, Neuromodulin, Chmp4b, DnaJB6, Vps37B, and Wasl. We extensively utilized bioinformatics tools, such as FuzDrop, D2P2, UniProt, RIDAO, STRING, AlphaFold, and ELM for comprehensive analysis of the intrinsic disorder propensity of these proteins. Our analysis suggested that these disordered host proteins might play a significant role in facilitating the rabies virus pathogenicity, immune system evasion, and the development of the antiviral drug resistance. Our study highlighted the complex interaction of the virus with its host, with the focus on how the intrinsic disorder can play a crucial role in virus pathogenic processes and suggested that these intrinsically disordered proteins (IDPs) and disorder-related host interactions can also be a potential target for the therapeutic strategies.

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%.

This study delves into the extraction and compositional analysis of soybean meal protein isolates (SMPI) compared to soy protein isolates (SPI), focusing on their functional and structural properties, digestibility, amino acid composition, and the impact of various proteases on antinutritional factors. By leveraging alkaline (0.25 % of NH4OH) extraction and isoelectric precipitation, SMPI was efficiently obtained. Compositional characteristics revealed that SMPI has high moisture, protein, and ash, but lower fat, and carbohydrate content compared to SPI. Alcalase, Neutrase and Pepsin hydrolysis indicated lower digestibility of SMPI than SPI. Fourier-transform infrared spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis provided similar molecular structure and protein molecular weight distribution. This comprehensive analysis underscores the valorization of soybean meal, promoting its use beyond conventional animal feed towards nutritional supplements and bio-based products, thereby contributing to environmental sustainability and the enhancement of global food systems.

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.

Background: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil activation status (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. Materials: The study is a secondary retrospective observational analysis. Clinical data upon ICU admission were collected. A control group of critically ill patients without sepsis criteria was included. Patients were divided into subgroups based on renal function for biomarker evaluation, with 28-day outcomes reported for septic and non-septic patients. Results: 200 patients were included in the study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65–59.05] vs. 48.00 [46.00–49.90], p< 0.001, respectively). NEUT-RI and PCT distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42 - 12.09] vs 32.59 [8.83 - 100.00], < 0.001 and NEUT-RI 51.50 [47.80 - 56.30] vs 56.20 [52.30 - 61.92], p=0.005). NEUT-RI, PCT and CRP values were significantly different in patients with “renal failure”. NEUT-RI and PCT at admission in ICU in septic group were higher in patients who died (58.80 [53.85-73.10] vs 53.05 [48.90-57.22], p=0.005 and 39.56 [17.39-83.72] vs 3.22 [0.59-32.32], p=0.002, respectively). Both NEUT-RI and PCT showed high negative predictive value and low positive predictive value. Conclusions: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission

Prenatal maternal feeding plays an important role in fetal development and has potential to cause long-lasting epigenetic modifications. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs that serve as one epigenetic mechanism. Though miRNAs have crucial roles in fetal programming, growth, and development, there are limited data regarding maternal diet and sheep miRNA expression. Therefore, weanalyzed high and low maternal dietary protein for miRNA expression in sheep fetal longissimus dorsi. Pregnant ewes were fed an isoenergetic high-protein (HP, 160–270 g/day), low-protein (LP, 73–112 g/day), or standard protein diet (SP, 119–198 g/day) during pregnancy. miRNA expression profiles were evaluated using the Affymetrix GeneChip miRNA 4.0 Array. Twelve up-regulated, differentially expressed miRNAs (DE miRNAs) were identified targeting 65 genes. The oar-3957-5p miRNA was highly up-regulated in LP and SP compared to HP. Previous transcriptome analysis identified integrin and non-receptor protein tyrosine phosphatase genes targeted by miRNAs detected in the current experiment. A total of 28 GO terms and 10 pathway-based gene sets were significantly (padj &lt; 0.05) enriched in target genes. Most genes targeted by identified miRNAs are involved in immune and muscle disease pathways. Our study shows dietary protein intake during pregnancy affects fetal skeletal muscle epigenetics via miRNA expression.

Fourteen Russian potato cultivars (cvs.) grown for three years in field plots of VIR (Northwestern region of the Russian Federation) were evaluated for productivity and a number of biochemical parameters of tubers. The 12 parameters that have been evaluated in tubers annually one month after harvesting and after cold storage (at 2 - 4°C) include the content of dry matter, starch, protein, ascorbic acid, carotenoids and β-carotene, anthocyanins, total sugars and monosaccharides (reducing sugars), phenolic compounds, as well as total acidity, and antioxidant activity. The cultivars differed significantly in productivity and biochemical composition of tubers. Dry matter content ranged from 16.40% in cv. ʻKumachʼ to 27.28% in ʻNayadaʼ, starch content ranged from 8.96 % in cvs. ʻFioletovyjʼ, ʻKumachʼ to 20.08% in ‘Sokur’, the total sugar content reached 2.46% in cv. ʻSiverskij’ whereas ‘Sokur’ has the smallest content of reducing sugars in post-harvest tubers. Protein content ranged from 1.02% to 2.77% with the highest accumulation in cv. ʻSokurʼ. Content of ascorbic acid (vitamin C) ranged from 6.3 mg/100 g FW in ʻKrasa Meŝeryʼ to 26.6 mg/100 g FW in cv. ʻKrasavchikʼ. Carotenoids content ranged from 0.157 mg/100 g FW in cv. ‘Nayada’ to 0.645 mg/100 g FW in cv. ʻGrandʼ. Content of anthocyanins in potato ranged from 1.04 mg/100g FW (not colored tubers of cv. ʻKrasa Meŝeryʼ) to 283.04 mg/100g FW (colored tubers of cv. ʻFioletovyiʼ). The nutritional value of tubers (content of dry matter, sugars, starch and protein) was determined to a greater extent (38-49%) by varietal characteristics, rather than by meteorological conditions in vegetation period. The content of vitamin C, carotenoids, protein and anthocyanins varied depending on the year. The highest content of dry matter, starch and carotenoids was noted in tubers harvested in 2019, marked by low temperatures and precipitation deficit in growing season. The conditions of 2020 with low temperatures and excess precipitation were the most favorable for anthocyanin’s accumulation in potato tubers while not for other biochemical parameters. Of the cultivars, ʻSokurʼ had the highest content of dry matter, protein and starch. Cv. ʻFioletovyiʼ had small starch content and high level of anthocyanins. Cv. ʻPlamyaʼ can be recommended for potato products manufacturing due to dry matter content above 20% and reducing sugars content 0.24%..

The cucumber mosaic virus (CMV) 2b protein is a suppressor of plant defenses and a pathogenicity determinant. Amongst the 2b protein’s host targets is the RNA silencing factor Argonaute 1 (AGO1), which it binds to and inhibits. In Arabidopsis thaliana, if 2b-induced inhibition of AGO1 is too efficient it induces reinforcement of antiviral silencing by AGO2, and triggers increased resistance against aphids, CMV’s insect vectors. These effects would be deleterious to CMV replication and transmission, respectively, but are moderated by the CMV 1a protein by sequestering sufficient 2b protein molecules into P-bodies to prevent excessive inhibition of AGO1. Mutant 2b protein variants were generated and red and green fluorescent protein fusions used to investigate subcellular colocalization with AGO1 and the 1a protein, and the effects of mutations on complex formation with the 1a protein and AGO1 were investigated using bimolecular fluorescence complementation and co-immunoprecipitation assays. Although we found that residues 56-60 influenced the 2b protein’s interactions with the 1a protein and AGO1, it appears unlikely that any single residue or sequence domain is solely responsible. In silico predictions of intrinsic disorder within the 2b protein secondary structure were supported by circular dichroism (CD) but not by nuclear magnetic resonance (NMR) spectroscopy. Intrinsic disorder provides a plausible model to explain the 2b protein’s ability to interact with AGO1, the 1a protein and other factors. However, the reasons for the conflicting conclusions provided by CD and NMR must first be resolved.

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.

: Considering that Einstein's relation between the diffusion coefficient and the drift mobility of the free randomly moving charge carriers in homogeneous materials including metals is always valid, it is shown that the effective electric force acting on free electrons in metal depends on the ratio between the kinetic free electron energy at the Fermi surface to the classical particle energy 3kT/2. The electrical resistivity of elemental metals dependence on very low temperatures has the quadratic term, which has been explained by electron-electron scattering. In this paper, it is shown that the quadratic term of the electrical resistivity at low temperatures is caused by scattering of the free RM electrons by electronic defects due to linear effective free electron scattering cross-section dependence on temperature, but not by electron-electron scattering.

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease.

This article introduces a novel payload structure, which has been experimentally proven to have smaller impact force while the carried internal electronics remains intact. The study describes in details how materials and geometric structures were chosen based on information analysis. It is clarified how possible geometric structures and materials can be chosen to yield optimal efficiency. Finite element method simulations were carried out to investigate the mechanical properties of several geometric structures, which has led to the dodecahedron form. For the frame, Polylactic Acid were chosen as an optimal material. A low air pressure test for parts of the structure, and also the whole structure were carried out with successful results. Drop tests, with force measuring sensors and high speed videos, were carried out for measuring and comparing the maximal impact force of classical payloads and the novel one. Laboratory and real life tests demonstrated that the developed new structure is safer and it is applicable.

The evolution of human societal dynamics over the course of decades and centuries has led to an ever-increasingly complex digital modern life, one of the hallmark of which is the need for multi-tasking, inclusive of that with media. Is there an empirical mapping between this macroscopic (digital) evolution of the human societal dynamics (in terms of multi-tasking) and the microscopic evolution of the functional molecular units within cells (i.e., proteins) and their manifold cross-talks? Multi-tasking requires a certain degree of intrinsic or adapted flexibility which is as true at the bio-molecular level. Evolutionary diversification of structure-function relationship in proteins emphasizes the functional importance of intrinsically disordered entities (IDPs/IDRs) which are highly dynamic biological soft matters. Multi-functionality is favorably supported by their fluid-like shapes and other new malleable members of the protein family. The new wealth of knowledge coming from recent research on protein intrinsic disorder, fold-switching, moonlighting, hub proteins etc. has given us new insights into protein structure – functional relationship. This has led to a paradigm shift in protein science, clearly diverging from the traditional 'one structure – one function' model applicable to enzyme classes to a more complex understanding of protein functionality. This paradigm shift has caused scientists to delve deeper into the subject, exploring various evolutionary toys and tools to fit the cumulative multi-functional demands in higher organisms. This commentary covers the different evolutionary arsenals to achieve the growing multi-functionality and argues in favor of protein intrinsic disorder as probably the sharpest weapon of all.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

The coronavirus pandemic was declared by the World Health Organization (WHO) in 2020, and a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, many countries around the world have reported that so-called genetic vaccines, such as those using modified mRNA encoding the spike protein and lipid nanoparticles as the drug delivery system, have resulted in post-vaccination thrombosis and subsequent cardiovascular damage, as well as a wide variety of diseases involving all organs and systems, including the nervous system. In this article, based on these circumstances and the volume of evidence that has recently come to light, we call the attention of medical professionals to the various risks associated with blood transfusions using blood products derived from people who have suffered from long COVID and from genetic vaccine recipients, including those who have received mRNA vaccines, and we make proposals regarding specific tests, testing methods, and regulations to deal with these risks. We expect that this proposal will serve as a basis for discussion on how to address post-vaccination syndrome and its consequences following these genetic vaccination programs.

This paper provides an overview of current literature on community-led development initiatives in urban contexts, their role in addressing urban inequality, and the challenges they face. This study examines effective strategies of community-led initiatives, such as empowering communities, building partnerships, mobilizing resources, focusing on local needs, and participatory design methods. Case studies from around the world demonstrate how successful community-led development initiatives have been able to overcome obstacles to create more inclusive and equitable urban environments. Institutional support, including technical assistance, capacity building, and regulatory frameworks, are crucial for promoting the success and sustainability of these initiatives. Challenges to community-led initiatives include limited resources, capacity building needs, inadequate infrastructure, lack of institutional support, and lack of trust among community members. Therefore, the paper suggests that it is essential to address these challenges to enable the success of community-led development initiatives. Furthermore, this study recommends that future research should explore how emerging technologies and innovative approaches can effectively support community-led development initiatives and advance more just and sustainable urban development.

Abstract: Kiwifruit, a perennial horticultural crop known for its nutritional value, faces significant challenges due to biotic and abiotic stresses, affecting its yield and quality. Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we investigated the expression patterns of kiwifruit LRR-RLPs under various stress conditions, including pathogen stress, heat stress, waterlogging stress, and copper stress. Through genome and transcriptome analyses, we identified a total of 101, 164, and 105 LRR-RLPs in Actinidia Chinensis 'Hongyang', Actinidia eriantha 'Huate', and Actinidia chinensis 'Red5' kiwifruit, respectively, classified into 9 subgroups based on phylogenetic relationships. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Using RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP genes in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.

The recent setbacks in the withdrawal and approval delays of antibody treatments of neurodegenerative disorders (NDs) can be attributed to their poor entry across the blood-brain barrier (BBB). While several invasive and noninvasive approaches can be used to make the BBB more permeable, their inconsistency makes them a poor choice; however, if an antibody is chemically modified to attach a transferrin molecule that enhances its permeation across the BBB, this could be the most practical and useful modification that can transform the science of ND treatment. Antibodies can be conjugated with transferrin in vitro, but preferably through mRNA, as we propose to convert current treatments to bring faster treatment options. The mRNA technology yields products at a meager cost, which is a consideration for the affordability of these drugs globally. This paper provides complete details with templates to convert the current medicines and those under development into mRNA delivery systems to ensure clinical success, avoiding the current failures in their efficacy, more specifically the products that have demonstrated efficacy but are being removed from the market.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.