Natural products from plants such as, chemopreventive agents attract huge attention because of their low toxicity and high specificity. The rational drug design in combination with structure based modeling and rapid screening methods offer significant potential for identifying and developing lead anticancer molecules. Thus, the molecular docking method plays an important role in screening a large set of molecules based on their free binding energies and proposes structural hypotheses of how the molecules can inhibit the target. Several peptide based therapeutics have been developed to combat several health disorders including cancers, metabolic disorders, heart-related, and infectious diseases. Despite the discovery of hundreds of such therapeutic peptides however, only few peptide-based drugs have made it to the market. Moreover, until date the activities of cyclic peptides towards molecular targets such as protein kinases, proteases, and apoptosis related proteins have never been explored. In this study we explore the in silico kinase and protease inhibitor potentials of cyclosaplin as well as study the interactions of cyclosaplin with other cancer-related proteins. Previously, the structure of cyclosaplin was elucidated by molecular modeling associated with dynamics that was used in the current study. Docking studies showed strong affinity of cyclosaplin towards cancer-related proteins. The binding affinity closer to 10 indicated efficient binding. Cyclosaplin showed strong binding affinities towards protein kinases such as EGFR, VEGFR2, PKB and p38 indicating its potential role in protein kinase inhibition. Moreover, it displayed strong binding affinity to apoptosis related proteins and revealed the possible role of cyclosaplin in apoptotic cell death. The protein-ligand interactions using LigPlot displayed some similar interactions between cyclosaplin and peptide-based ligands especially in case of protein kinases and a few apoptosis related proteins. Thus, the in silico analyses gave an insight of cyclosaplin as a potential apoptosis inducer and protein kinase inhibitor.

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

Sub-micron o/w emulsions coated with chitosan have been used for drug delivery, quorum sensing inhibition and vaccine development. To study interactions with biological systems, nanocapsules have been fluorescently labelled in previous works, but it is often difficult to distinguish the released label from intact nanocapsules. In this study, we present advanced labelling strategies based on FRET measurements for chitosan-coated nanocapsules and investigate their dissolution and degradation. We used FRET measurements of nanocapsules loaded with equimolar concentrations of two fluorescent dyes in their oily core and correlated them with DLS count rate measurement and absorbance measurements during their disintegration by dissolution. Using count rate measurements, we also investigated the enzymatic degradation of nanocapsules using pancreatin and how protein corona formation influences their degradation. Of note, nanocapsules dissolved in ethanol, where FRET decreased simultaneously with count rate, and absorbance caused by nanocapsule turbidity, indicating increased distance between dye molecules after their release. Nanocapsules were degradable by pancreatin in a dose dependent manner, and showed a delayed enzymatic degradation after protein corona formation. We present here novel labelling strategies for nanocapsules that allow us to judge their status and an in vitro method to study nanocapsule degradation and the influence of surface characteristics.

Brevibacillus laterosporus (Bl) is a Gram-positive and spore-forming bacterium belonging to the Brevibacillus brevis phylogenetic cluster. Globally, insect pathogenic strains of the bacterium have been isolated, characterised, and some activities patented. Two isolates, Bl 1821L and Bl 1951, exhibiting pathogenicity against the diamondback moth and mosquitoes, are under development as a biopesticide in New Zealand. However, due to the suspected activity of putative antibacterial proteins (ABPs), the endemic isolates often grow erratically. Various purification methods including size exclusion chromatography, sucrose density gradient centrifugation, polyethylene glycol precipitation, and ammonium sulphate precipitation employed in this study enabled the isolation of two putative antibacterial proteins of ~30 kD and ~48 kD from Bl 1821L and one putative antibacterial protein of ~30 kD from Bl 1951. Purification of the uninduced cultures of Bl 1821L and Bl 1951 also yielded the protein bands of ~30 kD and ~48 kD on SDS-PAGE which indicated their spontaneous induction. Disc diffusion assay was used to determine the antagonistic activities of the putative ABPs. Subsequent transmission electron microscope (TEM) examination of purified putative antibacterial protein-containing solution showed the presence of encapsulin (~30 kD) and polysheath (~48 kD) like structures. Although only the ~30 kD protein was purified from Bl 1951, both structures were seen in this strain under TEM. Furthermore, while assessing the antibacterial activity of some fractions of Bl 1951 against Bl 1821L in size exclusion chromatography method, population of Bl 1821L persister cells was noted. Overall, this work added a wealth of knowledge for the purification of the HMW proteins (bacteriocins) of the Gram-positive bacteria including Bl.

The pharmaceutical market consists mainly of chemical and biological drugs. These drugs act on different types of targets and have distinct pharmacological properties. Generally, chemical drugs bind to the active site of target enzymes and easily penetrate the cell membrane owing to their small size; however, biological drugs can bind to the protein–protein interaction site but are less stable due to their protein properties. Cyclic peptides possess the pharmacological merits of both chemical and biological drugs, such as the ability to bind to the protein–protein interaction site and penetrate cell membranes. In this study, we developed a simple two-step system to generate a cyclic peptide library using the split intein of Npu DnaE and Gateway cloning. The first step is the PCR of Ready-to-use(R) template DNA having the coding sequences of random cyclic peptides between two split intein elements NpuC and NpuN and the recombination recognition site of Gateway cloning. The second step is the transformation of the PCR products via Gateway cloning to produce colonies with expression vectors to produce cyclic peptides comprising random amino acid sequences. The expression vectors in randomly chosen transformed colonies were confirmed to have random cyclic peptide sequences and all the clones, except ones having a stop codon in the cyclic peptide coding region, showed the expected protein splicing result. This simple two-step system for bacterial expression systems may be modified to suit various expression systems for cell-based assays.

Acetylcholine (ACh) is the best one characterized neurotransmitter. Its central roles in the cholinergic areas and central nervous system (CNS) and peripheral (PNS) synapses are well known. It was the first molecule identified as a neurotransmitter and appears to be phylogenetically the oldest one signaling molecules. ACh was detected in bacteria, protozoa, fungi, algae and primitive plants, indicating that the cholinergic system was widely distributed in living organisms before its appearance in the nervous system. The autonomous nervous system (ANS) is an integral part animal kingdom history. It determines fight-escape reactions as well as outlining the vital and cognitive functions bio-organization rhythms. The virus (Covid-19) extraneous effects acting on it could help to better understand its functions. The Blast results show some factors like protein that can be implicated such as bungaro-toxins, phospholipase A2 and the similar prothrombin activator protein. A positive correlation with different toxins is obtained and the Covid-19 double pathogenic mechanism theory is proposed. The process allows us to outline the possibility about toxic-like factors presence.

Myocardial infarction, more commonly known as heart attack, is a huge health problem around the world. It is a result of inadequate blood supply to certain parts of the heart and death of heart muscle cells in that region. Although it has been around for a long time, newer and newer ways of probing myocardial infarction is being followed. Bioinformatics and Systems Biology are relatively recent fields to try to give new insights into myocardial infarction. Following the footsteps of others, this in silico study has tried to chime in on the investigation into myocardial infarction. The study began with the gene expression omnibus dataset uploaded to the NCBI from a whole-genome gene expression analysis carried out at Mayo Clinic in Rochester, Minnesota. From the dataset, differentially expressed genes following first-time myocardial infarction were identified and classified into up-regulated and down-regulated ones. Gene Set Enrichment Analysis (GSEA) was carried out on the up-regulated genes which were statistically significant and corresponded with the NCBI generated annotations. Protein-Protein Interaction Network for these genes was constructed. GSEA revealed 5 transcription factors, 5 microRNAs and 3 pathways significantly associated with them. From the Protein-Protein Interaction Network, 6 key proteins (hub nodes) have been identified. These 6 proteins may open a new window of opportunity for the discovery/design of new drugs for mitigating the damage caused by myocardial infarction.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has increased meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

Thermal plasma is a versatile technology that can be used to treat various types of wastes, including vegetal and mineral oils, solvents, plastics, papers and cardboard, glasses, bricks and rocks, metals, clothes, and mixtures of these materials. In this study, we utilized a commercial plasma cutter as a thermal plasma source to decrease the volume of a simulated low-level radioactive mixed solid waste. The simulated waste included papers, plastics, clothes, gloves, metals and stable Co, Cs, Sr, and Ce additives as surrogates of 60Co, 137Cs, 90Sr, and 144Ce, the latter typical contaminants in nuclear LLW. As a result of the process two products were obtained, a solid phase in which we focused this work and a gaseous phase. To retain as much as possible surrogates in the solid final phase, crushed glass from broken bottles was included as a vitrification additive to the original waste. After undergoing heat treatment, a dense vitreous slag was produced and ashes. The process resulted in a volume reduction of 70%, indicating the successful gasification of organic excess materials. The surrogate elements were retained in the process and were found in the ashes composition: Co (3.4% w/w), Cs (37.7% w/w), Ce (0.6% w/w) and in the glass matrix composition of Co, Cs, Sr and Ce: 72.4 ± 14.7, 32 ± 18.2, 125.3 ± 31.6, 80 ± 13.1 % w/w respectively. For the actual experimental conditions, retention efficiencies were estimated for Cobalt (Co) at 72.4 ± 14.7%, Cerium (Ce) at 80 ± 13.1%, Strontium (Sr) at 125.3 ± 31.6%, and notably Cesium (Cs) at 32 ± 18.2%.

The use of low cost sensors has dramatically increased in recent years in all the engineering sectors. In the field of buildings and automotive, low cost sensors open very interesting perspectives, because they allow to monitor temperature and humidity distributions together with air quality, in a widespread and punctual way and allow control of all energy parameters. The main issue still open remains the validation of the measurements. In this work, we propose an innovative approach to verify the measurements given by some low-cost systems built ad hoc for automotive applications. Two independent low-cost measurement systems have been set to measure Particulate air Matter (PM) concentration, TVOC concentration, CO2 concentration, formaldehyde concentration, air temperature, relative humidity, pressure, air flow velocity and GPS position. These systems have been calibrated by the comparison with standard and certified sensors used by the regional authority of Emilia-Romagna region (ARPAE, Italy) for characterising the air-quality. The innovation of this approach lies in both the in-field comparison of low-cost and high quality sensors and the use of proper conversion approaches for mass concentration measurements. A quantitative analysis of the sensors performance is given, with a focus on effects of time-granularity, relative humidity, mass conversion from particle counts and size detection response. The results show that the low-cost sensors measurements of air temperature, relative humidity and particle number concentration are in a good agreement with high quality sensors measurements, with a strong impact of relative humidity on performance indicators. Overall, a good quality and consistency of the data among the sensors has been achieved.

The objective of this study is to develop a predictive model for low-carbon bainitic steel utilising the P and λ parameters. The tempering activation energy of the steel was calculated through statistical methods. Kinetic curves for the hardness equivalents and a nomograph for tempering process parameters were plotted. The error analysis indicates that the predicted values based on the λ and P parameters had errors within 15% and 10%, respectively. The model can be effectively utilised to predict mechanical properties and optimise parameters during the tempering process.

This study investigated the efficiency of scale-propellers, typically used on small drones. A scale-propeller is accepted as having a diameter of 7 to 21 inches. The Ukraine War has demonstrated the utility of relatively small, low-cost first-person view (FPV) drones, which are attritable. This investigation outlines the development of a MATLAB optimisation code, based on minimum induced loss propeller theory, which calculates the optimal chord and twist distribution for a chosen propeller operating in known flight conditions. The MATLAB code includes a minimum Reynolds number functionality, which provides the option to alter the chord distribution to ensure the entire propeller is operating above a set threshold value of Reynolds (&gt;100,000), as this has been found to be a transition point between low and high section lift-to-drag ratios. Additional functions allow plotting of torque and thrust distributions along the blade. The results have been validated on experimental data taken from an APC ‘Thin Electric’ 10” x 7” propeller, where it was found that both the chord and twist distributions were accurately modelled. The MATLAB code resulted in a 16% increase in the maximum propulsive efficiency. Further work will investigate a direct interface to SolidWorks to aid rapid propeller manufacturing capability.

The growing interest in benchtop NMR systems is visible in a vast number of applications in science and industry. Low-field nuclear magnetic resonance (LF-NMR) became an instant in technologies that productions are dependent on the reliable structure identification, grade and purity control, chemical process inspection or reaction monitoring. Beyond the benefits of being cost-, space-, maintenance- and user friendly, insufficient sensitivity and low signal resolution are the main drawbacks, due to which the low-field NMR (LF-NMR) in the fields of organic chemistry and synthesis remains limited to solely academic teaching purposes. Herein, we discuss the possibilities of LF-NMR for the needs of organic chemistry and synthesis on a set of compounds 1-4 achieved as the products of student’s laboratory course and organic derivatives 5-8 that are from our research interests. Chemical structure determination of all compounds 1-8 presented herein was performed using the benchtop-type NMR instrument operating at 60 MHz (Pulsar Oxford Ltd.). Structure of novel compounds 5-7 prepared under the aims of our research was characterized by combined 1H/19LF-NMR and compared with an appropriate high-field NMR data from Bruker Ascend Instrument (400 MHz). Finally, possibilities of the low-field NMR as an analytical tool for the research purposes in the fields of organic chemistry and synthesis are documented on a set of 1H and 2D 1H-1H COSY for azomethine 8.

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.

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.

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

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.

In recent years, researches on combining wavelet decomposition and convolutional neural network (CNN) together to classify hyperspectral images (HSI) have emerged, and some effective classification models have been proposed and achieved good classification results. However, there are two problems for most of the proposed models. One is the heavy training parameters and the other is that there is no distinction between the classification effectiveness of low frequency and high frequency features after wavelet decomposition. In this paper, a new light-weighted HSI classification model (LLFWCNN) is proposed, which performs multi-layer wavelet decomposition for HSI after dimensionality reduction, and only arranges the low frequency features in a specific stack mode, then classifies them through a well-designed convolutional neural network. Compared with other classification models, the number of parameters is only 2.5% of that of other models. And only the low frequency features after wavelet decomposition are used, while the high frequency features are abandoned. The results showed that compared with the state-of-the-art classification models, LLFWCNN could obtain the same or even better classification results with fewer network parameters and proved that the low frequency features after wavelet decomposition provide LLFWCNN with more favorable information for HSI classification as well.

A multicenter, prospective cohort study conducted in 5 physiotherapy clinics in the UAE from January 2021 to March 2023 to assess coronal lumbar spine radiographic parameters as a predictor of conservative therapy outcomes in patients suffering from low back and leg pain due to lumbar disc herniation (HNP). Ninety patients (mean age 44 yrs., 54% male) with lumbar HNP underwent conservative therapy. All participants received lumbar spine MRI and radiography to assess spine alignment. Interventions included specific exercises, diathermy, traction, education, a home-based exercise pro-gram, and medications. Detailed demographic data was collected. Follow-up was 6-months after discharge. A successful outcome was based on a minimum of the following four outcomes: (1) reduction of pain by 17.5 points (0–100 NRS); (2) fatigue reduction by 7.5 points; (3) distress reduction by 5 points; and (4) interference reduction by 9.5 points. At 6-month follow-up it was found that patient age, education, and radio-graphic determined lumbosacral angle measures significantly affected the odds of a successful outcome. Increasing age 1-year significantly decreased the odds of success of improving pain, fatigue (OR = 0.85, p = 0.016) and interference scores (OR = 0.89, p = 0.042) by 15%, 15%, and 11% respectively. Lower education significantly increased the odds of success for improving pain, fatigue, and interference by 26.18, 26.18, and 7.5 (p = 0.006, = 0.006, and = 0.029 respectively). Increasing (worsening) the radiographic lumbosacral angle by each 1° significantly reduced the odds of success for improving pain, fatigue, distress, and interference by 3.52, 3.52, 27.99, and 2.55, respectively (p < 0.001, < 0.001, = 0.003, = 0.001). Our findings indicate that younger age, less education, and better coronal radiological lumbar spine alignment all had a substantial impact on the likelihood of success of 6-month outcomes in patients suffering from chronic lower back pain and radiculopathy due to HNP.

Greenhouse gas (GHG) emissions from human activities have climbed significantly above pre-pandemic levels and reached record highs that unequivocally accelerate global warming. Industry has a significant impact on climate change, emitting at least 21 % of global GHGs and making little overall progress toward its reduction until now. Reducing industry’s emissions requires coordinated action along the value chains in order to promote mitigation options, such as energy and material efficiency, circular material flows, and transformative changes within production processes. The authors analyzed the GHG emissions generated during the manufacturing of three different products of automotive suppliers located in Austria. Despite previous efforts toward an environmentally compatible fabrication, additional and significant reduction potentials were identified. These measures for product carbon footprint (PCF) reduction included the sourcing of low-carbon materials (which are already available on the market), more extensive use of renewable energy, and changes towards more resource efficient manufacturing processes and machinery. Depending on the materials used, the PCF can be reduced by up to 80 %. The findings serve to prepare for future PCF reporting regulations and illustrate reduction potentials to achieve future market advantages, especially when PCFs become an awarding criterion.

Previous studies on the mechanisms underlying willed actions reported that the premotor cortex may be involved in the construction of motor awareness. However, its exact role is still under investigation. Here we investigated the role of the dorsal premotor cortex (PMd) in motor awareness by modulating its activity applying inhibitory rTMS to PMd, before a specific motor awareness task (under three conditions: without stimulation, after rTMS and after sham stimulation). During the task, subjects had to trace straight lines to a given target, receiving a visual feedback of the line trajectories on a computer screen. Crucially, in most trials the trajectories on the screen were deviated and to produce straight lines, subjects had to correct their movements towards the opposite direction. After each trial, participants were asked to judge whether the line seen on the computer screen corresponded to the line actually drawn. Results show that participants in the no stimulation condition did not recognize the perturbation until 14 degrees of deviation. Importantly, active, but not sham, rTMS significantly modulated motor awareness, decreasing the amplitude of the angle at which participants became aware of the trajectory correction. These results suggest that PMd plays a crucial role in action self- monitoring.

The study of velocimetry is important for characterizing and comprehending the effects of fluid flow, and the Particle Image Velocimetry (PIV) technique is one of the primary approaches for understanding the velocity vector field in a test section. Commercial PIV systems are expensive, with one of the main cost factors being high-speed camera equipment capable of capturing images at high frames per second (fps), rendering them impractical for many applications. This study proposes an evaluation of utilizing smartphones as image acquisition systems for PIV technique application. An experimental setup inspired by the known angular displacement of synthetic particles is proposed. A stepper motor rotates a plate containing an image of synthetic particles on its surface. The motion of the plate is captured by the smartphone camera, and the images are processed using PIVlab-MatLab® software. The use of two smartphones is assessed, with acquisition rates of either 240 fps or 960 fps and varying angular velocities. The results were satisfactory for velocities up to 0.7 m/s at an acquisition rate of 240 fps and up to 1.8 m/s at 960 fps, validating the use of smartphones as a cost-effective alternative for the PIV technique.

Worldwide, 200 million children experience disability, with the vast majority living in low and middle-income countries. The United Nations Convention on the Rights of the Child (CRC) places great importance on the rights of all children for the opportunities for survival, growth, health, and development. A subsequent document, the UN Convention on the Rights of Persons with Disabilities (CRPD) identifies children with disabilities as rights bearers, who should be considered in all policies and programming worldwide. Nigeria, in 1991 and 2010 ratified the CRC and the CRPD respectively. Nonetheless, knowledge of the extent to which their disability and child-directed policies are considered by these two key conventions remains limited. This study examined the extent to which Nigeria’s current disability and childhood policies have integrated the two normative frameworks from the UN. Using a structured search of databases and Nigerian federal and state government websites, we conducted a policy review to identify their disability and child-related disability policies. We also included the CRC and CRPD reports submitted by the Nigerian government to the United Nations Office of the High Commissioner for Human Rights (OHCHR) (2008 &amp; 2010 cyclical year). A thematic analysis, based on the CRC and CRPD report, identified the following six themes: participation, support systems, awareness-raising, factors associated with adherence to the CRC, laws &amp; rights, and services. The review showed that the available Nigerian disability policies were federal, with some state policies which aligned with the CRC and CRPD. Also identified was the lack of disability policies specific to children and their families. We concluded that, to ensure proper inclusion of the rights of all children, including those with disabilities, in Nigeria there is a need for a more optimal uptake of recommendations of the CRC and CRPD as laid out by the UN.

Low back pain (LBP) is a common musculoskeletal complaint that can impede physical function and mobility. Current management often involves pain medication, but there is a need for non-pharmacological and non-invasive interventions. Soft tissue manipulation (STM) such as massage has been shown to be effective in human subjects, but the molecular mechanisms underlying these findings are not well understood. In this paper, we evaluated potential changes in soft tissue levels of more than thirty pro- or anti-inflammatory cytokines following instrument-assisted STM (IASTM) in rats with chronic, induced LBP using Complete Freund’s Adjuvant. Our results indicate that IASTM is associated with reduced soft tissue levels of RANTES/CCL5 and increased soft tissue levels of IL-4, which are pro-inflammatory and anti-inflammatory factors, respectively, by 120 minutes post-treatment. IASTM was not associated with tissue-level changes in CXCL5/LIX (the murine homologue of IL-8), CXCL7, GM-CSF ICAM-1, IL1-ra, IL-6, IP-10/CXCL10, L-selectin, TNF-α, or VEGF at either 30- or 120 minutes post-treatment. Combined, our findings suggest that IASTM exerts tissue-level effects that are associated with improved clinical outcomes and potentially beneficial changes in pro/anti-inflammatory cytokines in circulation and at the tissue level.

In order to monitor the diversity of terrestrial biomes, the Earth Exploration Satellite Services demand a high data rate for downlink transmissions while sharing their frequency spectrum with, and suffering interferences from, cellular Base Stations. Both highlight the dilemmas of spectral efficiency (bps/Hz) and spectral coexistence. Our research aims to mitigate interference on low orbit satellite downlinks using Cognitive Radio (CR) and Adaptive MODulation and CODing (MODCOD) techniques. To fulfill this: 1) we present CR approaches to enhance spectrum exploitation. Next, 2) we detail Adaptive MODCOD (ACM) technique to increase RF power and spectral efficiencies. Then, 3) we suggest the solution by combining 1) and 2). Afterwards, 4) we analyze it by monitoring the signal to interference plus noise ratio and the CR/MODCOD strategy. Finally, 5) we provide case studies to demonstrate the strategy’s effectiveness through the practical operation of satellite services, and 6) we conduct a bench test of the communication system.

With the advent of deep learning, significant progress has been made in low-light image enhancement methods. However, deep learning requires enormous paired training data, which is challenging to capture in real-world scenarios.To address this limitation, this paper presents a novel unsupervised low-light image enhancement method, which first introduces the frequency domain features of images in low-light image enhancement tasks. Our work is inspired by imagining a digital image as a spatially varying metaphoric “field of light”, then subjecting the influence of physical processes such as diffraction and coherent detection back onto the original image space via a frequency-domain to spatial-domain transformation (inverse Fourier transform). However, the mathematical model created by this physical process still requires complex manual tuning of the parameters for different scene conditions to achieve the best adjustment. Therefore, we proposed a dual-branch convolution network to estimate pixel-wise and high-order spatial interactions for dynamic range adjustment of the frequency feature of the given low-light image. Guided by the frequency feature from the “field of light” and parameter estimation networks, our method enables dynamic enhancement of low-light images. Extensive experiments have shown that our method performs well compared to state-of-the-art unsupervised, and its performance approximates the level of the state-of-the-art supervised methods qualitatively and quantitatively. At the same time, the light network structure design allows the proposed method to have an extremely fast inference speed(nearly 150 FPS on an NVIDIA 3090 Ti GPU for an image of size 600×400×3 ). Furthermore, the potential benefits of our method to object detection in the dark are discussed.

: We evaluated the pharmaceutical properties of levofloxacin (LV) in the form of an orally disintegrating tablet (LVODT) to find a new usefulness of low frequency (LF) Raman spectroscopy. LVODT contained dispersed granules with diameters in the order of several hundred micrometers, which were composed of the active pharmaceutical ingredient (API), as confirmed by infrared (IR) microspectroscopy. On the contrary, the API and inactive pharmaceutical ingredients (non-APIs) were homogeneously distributed in LV tablet (LVT) formulations. Microscopic IR spectroscopy and thermal analyses showed that LVODT and LVT contained the API in different crystalline forms or environment around the API each other. Furthermore, powder X-ray diffraction showed that LVT contained a hemihydrate of the API, while LVODT showed a partial transition to the monohydrate form. This result was confirmed by microscopic LF Raman spectroscopy. Moreover, this method confirmed the presence of thin layers coating the outer edges of the granules that contained the API. Spectra obtained from these thin layers indicated the presence of titanium dioxide, suggesting that the layers coexisted with a polymer that masks the bitterness of API. The microscopic LF Raman spectroscopy results in this study indicated new applications of this method in pharmaceutical science.

A low-profile broadband dual-polarized antenna is investigated for base station applications. It consists of two orthogonal dipoles, fork-shaped feeding lines, an artificial magnetic conductor (AMC), and parasitic strips. By utilizing the dispersion Brillouin diagram, the AMC is designed as the antenna reflector. It has a wide in-phase reflection bandwidth of 54.7% (1.54-2.70 GHz) and a surface wave bound range of 0-2.65 GHz. This design effectively reduces the antenna profile by over 50% compared to traditional antennas without an AMC. For demonstration, a prototype is fabricated for 2G/3G/LTE base station applications. Good agreement between simulations and measurements is observed. The measured -10-dB impedance bandwidth of our antenna is 55.4% (1.58 –2.79 GHz), with a stable gain of 9.5 dBi and high isolation of more than 30 dB across the impedance passband. As a result, this antenna is an excellent candidate for miniaturized base station antenna applications.

3D printing is commonly used to create complex objects at a low cost. It has also been applied in the fabrication of metamaterials and metasurfaces, which alter the propagation path of electromagnetic waves. These structures have diverse applications, including enhancing beam direction, improving antenna gain and signal-to-noise ratio, and creating filters and reflectors. Metasurfaces are cheap to fabricate and their use is expected to boost antenna efficiency in 5G telecommunications and beyond. However, accurately characterizing their profile remains a significant challenge. This paper presents a low-cost fully automated 4-axis instrument for microwave metasurface charac-terization, overcoming limitations of manual methods and offering an efficient and accurate approach. This research represents a significant advancement in microwave metasurface characterization, enabling sophisticated techniques to advance wireless communication technolo-gies, as it is the case of the future 5G and millimeter-wave communication systems. The equipment has an approximate cost of $1550 USD and was able to characterize a metalens with a focal distance of 20 cm designed for signals at 30 GHz. It was possible to create 2D and 3D profiles of the intensity distribution focused by the metalens and extract parameters such as the gain (8.05 dB), 3dB depth of focus (11 cm) and full width at half maximum (2.17 cm). The comparison of the measurements with the diffraction calculations of the metalens showed a very good agreement between the in-tensity distributions and the parameters of the metalens.

UV induced photoluminescence of organosilica films with ethylene and benzene bridging groups in their matrix and terminal methyl groups on the pore wall surface is studied to reveal optically active defects and understand their origin and nature. Careful selection of the film’s precursors and conditions of deposition and curing, analysis of chemical and structural properties led to the conclusion that luminescence sources are not associated with the presence of oxygen-deficient centers, as in the case in pure SiO2. It is shown that the sources of luminescence are the carbon-containing components that are part of the low-k-matrix, as well as the carbon residues formed upon removal of the template and UV induced destruction of organosilica samples. A good correlation between the energy of the photoluminescence peaks and the chemical composition is observed. This correlation is confirmed by the results obtained by the Density Functional theory. The photoluminescence intensity increases with porosity and internal surface area. The spectra become more complicated after annealing at 400 °C, although Fourier transform infrared spectroscopy does not show these changes. The appearance of additional bands is associated with compaction of low-k matrix and segregation of template residues on the surface of the pore wall.

Low-dimensional carbon-based (LDC) materials have attracted extensive research attentions in electrocatalysis because of their unique advantages such as structural diversity, low cost, and chemical tolerance. They have been widely used in a broad range of electrochemical reactions to relief environmental pollution and energy crisis. Typical examples include hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO₂RR), and nitrogen reduction reaction (NRR). Traditional “trial and error” strategies seriously slowed down the rational design of electrocatalysts for these important applications. Recent studies show that the combination of density functional theory (DFT) calculations and experimental research is capable of accurately predicting the structures of electrocatalysts, thus could reveal the catalytic mechanisms. Herein, current well-recognized collaboration methods of theory and practice are reviewed. The history of modern DFT, commonly used calculation methods, and basic functionals are briefly summarized. Special attention is paid to descriptors that are widely accepted as a bridge links the structure and activity, and the breakthroughs for high-volume accurate prediction of electrocatalysts. Importantly, correlating multiple descriptors are used to systematically describe the complicated interfacial electrocatalytic processes of LDC catalysts. In addition, machine learning and high-throughput simulations are crucial in assisting the discovery of new multiple descriptors and reaction mechanisms. This review will guide the further development of LDC electrocatalysts for extended applications from the aspect of DFT computations.

Background: Cervical cancer is the fourth most common cancer in women globally despite being a largely treatable and preventable malignancy. Developing countries account for over 80% of all new cases of cervical cancer. Women residing in low-resource settings such as those residing in slums have a higher risk of cervical cancer, and lower uptake of cervical cancer screening. Diverse barriers influence the uptake of cervical cancer screening among women in low-resource settings. Objectives: This qualitative study was carried out prior to a cervical cancer screening program and explored women’s knowledge about cervical cancer, and their perceived barriers and recommendations for the program.Method: Four focus group discussions (FGD) were conducted among 35 women between the ages of 21 – 65 years residing in two urban slums in Lagos, Nigeria. Each FGD was limited to 8-10 participants of women of similar ages. Voice recordings were transcribed verbatim and analysis was done using thematic analysis.Results: Most of the women were not aware of cervical cancer and none knew the symptoms or risk factors of cervical cancer. The participants felt that the cervical cancer screening program would be well accepted in the community, however, they expressed concerns about the cost of the screening test and the sex of the person performing the test. The recommendations proffered for a successful cervical cancer screening program include; reducing the cost of the test or providing the test free of charge, having people that speak the local language as part of the team, using female health care providers, using a private location within the community or nearby PHC, and publicizing the program with the use of SMS, phone calls, town crier, and health talks. It was recommended that organizing health education sessions would help improve women’s poorly perceived susceptibility to cervical cancer.Conclusion: Interventions to increase uptake of cervical cancer screening among women in low resource settings need to improve knowledge and understanding of cervical cancer and address the barriers to cervical cancer screening such as cost, distance, and as much as possible, sex of the healthcare provider should be considered.

We present improvements in n-best rescoring of code-switched speech achieved by n-gram augmentation as well as optimised pretraining of long short-term memory (LSTM) language models with larger corpora of out-of-domain monolingual text. In addition, we consider the application of large pretrained transformer-based architectures. Our experimental evaluation is performed on an under-resourced corpus of code-switched speech comprising four bilingual code-switched sub-corpora, each containing a Bantu language (isiZulu, isiXhosa, Sesotho, or Setswana) and English. We find in our experiments that, by combining n-gram augmentation with the optimised pretraining strategy, speech recognition errors are reduced for each individual bilingual pair by 3.51% absolute on average over the four corpora. Importantly, we find that even speech recognition at language boundaries improves by 1.14% even though the additional data is monolingual. Utilising the augmented n-grams for lattice generation, we then contrast these improvements with those achieved after fine-tuning pretrained transformer-based models such as distilled GPT-2 and M-BERT. We find that, even though these language models have not been trained on any of our target languages, they can improve speech recognition performance even in zero-shot settings. After fine-tuning on in-domain data, these large architectures offer further improvements, achieving a 4.45% absolute decrease in overall speech recognition errors and a 3.52% improvement over language boundaries. Finally, a combination of the optimised LSTM and fine-tuned BERT models achieves a further gain of 0.47% absolute on average for three of the four language pairs compared to M-BERT. We conclude that the careful optimisation of the pretraining strategy used for neural network language models can offer worthwhile improvements in speech recognition accuracy even at language switches, and that much larger state-of-the-art architectures such as GPT-2 and M-BERT promise even further gains.

This research refers to the creation of a method of medical technology such as a device that can collect, encode, temporarily store, and transfer electroencephalographic signals from epileptic patients for study and evaluation. For applying the specific apparatus related to neurostimulation technologies such as Deep Brain Stimulation (DBS) and Responsive Neurostimulation (RNS) the approaches followed concern three basic levels. The first level is concerned with initial modelling and creating the template for the following two stages. Further on, the second level is based on developing code for programming integrated circuits and simulation with the appropriate software. The third and final stage is the most substantial, as the transmitter’s construction is attempted at the evaluation level. In particular, more than one software and device are involved in this phase for the most realistic performance of the desired result. However, it is worth noting that the principal goal of this study is to achieve low consumption rates for the device’s complete and smooth operation. As a result, this research aims to evolve this device so that it can send data wirelessly and simultaneously provide energy efficiency.

Global malaria epidemiology has changed in the last decade with a substantial increase in cases and death being recorded. Over 90% of global cases and deaths occur in Sub-Saharan Africa (SSA). Tanzania accounts for about 4% of all cases and deaths reported in recent years. It is believed that several factors contribute to the resurgence of malaria, parasite resistance to antimalarials and mosquito resistance to insecticides being at the top of the list. The presence of sub-microscopic infections poses a significant challenge to malaria rapid diagnostic tests (mRDT), particularly in low-endemic areas. Our cross-sectional surveys in Handeni and Moshi, Tanzania assessed the effect of low parasite density on mRDT. A significant difference (P˂0.001) in malaria prevalence by mRDT, light microscopy (LM) and nested polymerase chain reaction (PCR) was found among age groups. In comparison to all other groups, school-age children (5-15 years) had the highest prevalence of malaria. Based on the results of this study, mRDT may miss up to 6% of cases of malaria mainly due to low-density parasitaemia. Routinely used mRDT will likely miss the sub-microscopic parasitemia which will ultimately contribute to the continued spread of malaria and hinder efforts to control and eliminate it.

During puberty and emerging sexuality, adolescents experience important physical, mental, and social transformations. In the process of dealing with these changes, adolescents can become potentially vulnerable to mental health problems.The aim was to identify and synthesize published research evidence on sexuality-related mental health stressors among adolescent girls and boys, identify gaps (if any) in current knowledge, and contribute to knowledge about the experiences of emerging sexuality and health among adolescents, to further inform research, practice, and policy initiatives in sexual health.A scoping literature review of peer-reviewed articles published between 1990 and 2018. MEDLINE, CINAHL, EMBASE, PsycINFO, Global health, ERIC, and Sociological Abstracts databases were searched for research studies that reported experiences of sexuality related mental health issues and symptomatology of adolescents. We targeted studies conducted with adolescent populations between ages 11-24 years living in LMICs.Data from 12 published research papers, including 8 qualitative studies, 3 quantitative studies, and 1 mixed method study, were systematically analyzed. Four major themes and 4 sub themes were identified regarding sexual health and mental health of adolescents: 1) Relationship of sexuality and mental health; 2) Social and cultural influences; 3) Challenges in seeking sexuality information and services among adolescents; and 4) Educational needs among adolescents related to sexuality; and 4) Educational needs among adolescents related to sexuality. Lack of social support, Unmet needs for accessible adolescent friendly sexual health services, counseling, and age-appropriate information may be associated with several mental health stressors and symptoms, such as sadness, depressive and anxiety symptomatology, regret, fear, embarrassment, low self-esteem, guilt, shame, and anger. Therefore, tackling sexuality-related stressors could play an important role in addressing the overall wellbeing of young people. Future studies need to generate a deeper understanding of the concept of sexual health and its relation to mental health in diverse contexts. Health care professionals need to be aware of sexuality-related experiences of adolescent girls and boys by offering effective youth-friendly sexual and reproductive health education to support overall mental health and improve the experiences of emerging sexuality in adolescents.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods are not sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, succeeded in the development of safer wheat varieties. However, these varieties had multiple challenges in their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit the immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of celiac-safe wheat variety and to establish it as a “tool to celiac safe wheat.”

The paradigm of the Somatic Mutation Theory (SMT) is failing and a new paradigm is in the making but not yet established. What is being challenged is a conceptual approach that involves the entire human biology and the development of chronic diseases. The behavior of breast cancer is well compatible with the concept that the primary tumor is able to control its microscopic metastases, in the same way that an organ (e.g., the liver) is able to control its physiological size. This finding suggested that breast cancer and its metastases may behave as an organoid. The new paradigm under construction considers the origin of tumors as a disturbance in the communication network between tissue cell populations and between cells and extracellular matrix, and supports a systemic approach to the study of both healthy and pathologic tissues. The commentary provides a rationale for the role of physical exercise in the control of tumor dormancy according to a human evolutionary perspective.

Low-frequency audible noise generated by the magnetostriction effect inherent to the operation of power transformers has become a major drawback, especially in cases where the electrical substation is located in urban areas subject to strict environmental regulations that imposes sound pressure limits, differing for day and night periods. Such regulations apply a +5 dB penalty if a tonal component of noise is present, which is clearly the case of magnetostriction noise, typically concentrated at twice the industrial frequency (50 Hz or 60 Hz, depending on the country). The strategy used to eliminate the tonal characteristics, therefore contributing to establish compliance with the applicable regulation and to alleviate the discomfort it causes to the human ear, consisted in superimposing to the substation noise a masking sound synthesized from “sounds of nature” with suitable intensities, to flatten the noise spectrum while enhancing the soundscape. The masking system (heavy-duty speakers powered by a microprocessor platform) was validated at an already judicialized urban scenario. Measurement results confirmed that the masking solution was capable of flattening the tonal frequencies, whose beneficial effect yielded the cancellation of the public civil action filed by the neighbors. The proposed solution is ready to be replicated to other scenarios.

Vehicle driveability is one of the important vehicle attributes in range-extender electric vehicles due to the electric motor torque characteristics at low-speed events. The process of validating and rectifying vehicle driveability attributes is typically utilised by a physical vehicle prototype that can be expensive and required several design iterations. In this paper, a model-based energy method to assess vehicle driveability is presented based on a high-fidelity 49 degree-of-freedom powertrain and vehicle systems. Multibody dynamics components were built according to their true centre of gravity relative to the vehicle datum for providing an accurate system interaction. The work covered a frequency at less than 20 Hz. The results that consisted of the component frequency domination are structured and examined to identify the low-frequency sensitivity based on different operating parameters such as a road surface coefficient. An energy path technique was also implemented on the dominant component by decoupling its compliances to study the effect on the vehicle driveability and low-frequency response. The outcomes of the research provided a good understanding of the interaction across the sub-systems levels. The powertrain rubber mounts were the dominant components that controlled the low-frequency contents (< 15.33 Hz) and can change the vehicle driveability quality.

Low back pain (LBP) is a leading cause of disability. It significantly impacts the patient’s quality of life, limits their daily living activities, and reduces work productivity. To reduce the burden of LBP, several pharmacological and non-pharmacological treatment options are available. This review summarizes the role of heat therapy in the management of LBP. First, we outline the common causes of LBP, then discuss the general mechanisms of heat therapy on (LB)P, and finally review the published evidence regarding the impact of heat therapy in patients with acute or chronic non-specific LBP. This review demonstrates that continuous, low-level heat therapy provides pain relief, improves muscular strength, and increases flexibility. Therefore, this effective, safe, easy-to-use, and cost-effective non-pharmacological pain relief option is still relevant in modern clinical practice.

This chapter is written for the welfare of the society, questioning and enlightening the effects of the increment or decrement in the percentage of quality of air causing pollution due to the rise in the traffic post-lockdown due to COVID-19 in metro cities, specifically in Delhi. In this chapter, we address the question about people's preference in moving in the shared taxis to their workplaces or their reluctance and denial of the idea of moving in the shared vehicle because of the fear of getting infected. The sensitivity of the situation will compel the people to move in a single occupied vehicle (SOV). The rise in the number of vehicles on the roads will result in traffic jams and different kinds of pollution where people battling with the pandemic will inevitably get exposed to other health-related issues. We use a BPR (Bureau of Public Roads) model to combat this issue endangering the environment and public health. We exploit the BPR function to relate average travel time to the estimated number of commuters travelling by car. We collect mode share data from the NITI Ayog, the State Resource Centre and other authentic sources, which gives unique figures of the impact of shared mobility in India and how, in its absence, various sectors will get affected. Using the given data and the BPR, we evaluate increased vehicle volumes on the road if different portions of transit and carpool users switch to single-occupancy vehicles and its effect on multiple other factors. Based on the study of densely populated city, Delhi, we predict that cities with significant transit ridership are at risk for extreme traffic and pollution unless transit systems can resume safe with effective protocols.

It is well known that low back pain (LBP) prevalence is high during the course of school age children’s lives. However, literature concerning the initial onset of back pain between ages of 3 and 11 years remains scarce. The present study aimed to analyze the prevalence of LBP in kindergarten and primary school students. 278 (9.9±2.1 years old; 52.2% girls) students from two public kindergarten and primary schools in Valencia, Spain participated in this cross-sectional study. The Nordic questionnaire on LBP was used to ask questions related to the duration of LBP symptoms over time. The lifetime prevalence of LBP was 47.5% (n = 132), a last year prevalence of 44.2% (n = 123), and a last week prevalence of 18.8% (n = 50) was reported. Boys and girls reached lifetime prevalence of 52.3% (n = 64) and 47.7% (n = 82) (χ2 = 1.978, p = .099), respectively. By age group, lifetime episodes of LBP also showed a higher prevalence with increasing age (χ2 = 32.637; p &lt; .001). In summary, our findings suggest that LBP increases with age. In addition, our results further strengthen the evidence that LBP onset could start as young as 10-years-old.

Crystallization is a significant procedure in the manufacturing of many pharmaceutical and solid food products. In-situ Electrical Resistance Tomography (ERT) is a novel Process Analytical Tool (PAT) to provide a cheap and quick way to test, visualize, and evaluate the progress of crystallization processes. In this work, the spatial accuracy of the non-conductive phantoms in low conductivity solutions was evaluated. Gauss-Newton, Linear Back Projection, and iterative Total Variation reconstruction algorithms were used to compare the phantom reconstructions for tap water, industrial-grade saturated sucrose solution, and demineralized water. Cylindrical phantom measuring 10 mm in diameter and a cross-section area of 1.5 % of the total beaker area was detected at the center of the beaker. Two phantoms with a 10 mm diameter were visualized separately in non-central locations. The quantitative evaluations were done for the phantoms with radii ranging from 10 mm to 50 mm in demineralized water. Multiple factors such as ERT device and sensor development, FEM mesh density and simulations, image reconstruction algorithms, number of iterations, segmentation methods, and morphological image processing methods were discussed and analyzed to achieve spatial accuracy. The development of ERT imaging modality for the purpose of monitoring crystallization in low conductivity solutions was performed satisfactorily.

Nowadays, the uses of laser and optics in the medical areas are extremely vivid, especially low-level laser therapy. The light with the wavelength of 633 nm to 1200 nm could penetrate and propagate deep in biological tissue. To develop the low-level laser therapy device, optimizing light delivery is critical to accurately stimulate the biological effects inside the biological tissue. Nevertheless, each form of the tissues at each zone on the body had various refractive optic, absorption, scattering, and anisotropy coefficients. This paper describes the simulation results of low-level laser propagation from skin surface at the lower spine, the knee, the femur and the prostate gland with four wavelengths (633 nm, 780 nm, 850 nm, and 940 nm) by the Monte Carlo method. These simulation results are the base for developing the low-level laser therapy device, that could be used in clinical for treating the fracture, knee osteoarthritis, spinal degeneration, and benign prostatic hypertrophy.

The Oil reservoirs with low permeability account for a large proportion in the world, they surpass half of the total number of the oil reservoirs in China, it is important to exploit this kind of reservoir effectively. The exploitive results of these reservoir using normal water flooding methods are very poor because of the thine pores, bad connections and so on. However, these problems can be well solved by applying gas injection techniques. In this paper, the effects on the recovery effects exerted by the injection parameters such as the oxygen content in the injected air, the injection speed etc. were studied by several experiments using independently designed equipments aiming at one low permeable sandstone reservoir in China. Several conclusions were made from the experiment results: the best recovery effects can be achieved by injecting the oxygen reduced air with 8% of oxygen at the speed of 0.3ml/min (7.41×10-4PV/min) using the methods of injecting the air slugs and the foaming agent slugs alternately; the best oxidation time of the oil was 168 hours and the final oil recovery could be enhanced by 26.5% in this method. It was also showed by the experiments that the larger the permeability ratio is, the larger the recovery factor will be increased. At last, several equations about relationships between the EOR and the air injection parameters were revealed according to the results of the experiments which may offer some references to the LTO process mechanisms study in the similar oil reservoir.

Microsystems are key enabling technologies, with applications found in almost every industrial field, including in-vitro diagnostic, energy harvesting, automotive, telecommunication, drug screening, etc. Microsystems, such as microsensors and actuators, are typically made up of components below 1000 microns in size that can be manufactured at low-unit cost through mass-production. Yet, the development of microsystems for commercial or educational purposes, has typically been limited to upper income countries due to the initial investment costs associated with the microfabrication equipment and processes. However, recent technological advances have enabled the development of low-cost microfabrication tools. In this paper, we describe a range of low-cost approaches and equipment (below £1000), developed or adapted and implemented in our laboratories. We describe processes including photolithography, micromilling, 3D printing, xurography and screen-printing used for the microfabrication of structural and functional materials. The processes that can be used to shape a range of materials with sub-millimetre feature sizes are demonstrated here in the context of Lab-on-Chips, but they can be adapted for other applications. We anticipate that this paper, which will enable researchers to build a low-cost microfabrication toolbox in a wide range of settings, will spark a new interest in microsystems.

We present the design, fabrication, and response of a polymer-based Laterally Amplified Chemo-Mechanical (LACM) humidity sensor based on mechanical leveraging and parametric amplification. The device consists of a sense cantilever asymmetrically patterned with a polymer and flanked by two stationary electrodes on the sides. When exposed to a humidity change, the polymer swells after absorbing the analyte and causes the central cantilever to bend laterally towards one side, causing a change in the measured capacitance. The device features an intrinsic gain due to parametric amplification resulting in an enhanced signal-to-noise ratio (SNR). 11-fold magnification in sensor response was observed via voltage biasing of the side electrodes without the use of conventional electronic amplifiers. The sensor showed a repeatable and recoverable capacitance change of 11% when exposed to a change in relative humidity from 25-85%. The dynamic characterization of the device also revealed a response time ~1s and demonstrated a competitive response with respect to a commercially available reference chip.

As an essential synthetic material used in continuous casting of steels, mold fluxes improve the surface quality of steel slabs. In this study, a CaO-SiO₂-Na₂O based low-fluorine mold flux was solidified by an improved water-cooled copper probe with different temperatures of molten flux and different probe immersion times. The heat flux through solid films and the film structures were calculated and inspected, respectively. The results indicate: large internal cracks (formed in the glassy layer of films during solidification) were observed, the formation and evolution of those cracks contributed to the the unstable heat flux density. The roughness of the surface in contacted with the water-cooled copper probe formed as films were still glassy and the roughness have no causal relationship with crystallization or devitrification. Combeite with columnar and faceted dendritic shapes is the main crystal in the film.

Identifying group movement patterns of crowds and understanding group behaviors is valuable for urban planners, especially when the groups are special such as tourist groups. In this paper, we present a framework to discover tourist groups and investigate the tourist behaviors using mobile phone call detail records (CDRs). Unlike GPS data, CDRs are relatively poor in spatial resolution with low sampling rates, which makes it a big challenge to identify group members from thousands of tourists. Moreover, since touristic trips are not on a regular basis, no historical data of the specific group can be used to reduce the uncertainty of trajectories. To address such challenges, we propose a method called group movement pattern mining based on similarity (GMPMS) to discover tourist groups. To avoid large amounts of trajectory similarity measurements, snapshots of the trajectories are firstly generated to extract candidate groups containing co-occurring tourists. Then, considering that different groups may follow the same itineraries, additional traveling behavioral features are defined to identify the group members. Finally, with Hainan province as an example, we provide a number of interesting insights of travel behaviors of group tours as well as individual tours, which will be helpful for tourism planning and management.

Due to an increase in the number of image achieves, Content-Based Image Retrieval (CBIR) has gained attention for research community of computer vision. The image visual contents are represented in a feature space in the form of numerical values that is considered as a feature vector of image. Images belonging to different classes may contain the common visuals and shapes that can result in the closeness of computed feature space of two different images belonging to separate classes. Due to this reason, feature extraction and image representation is selected with appropriate features as it directly affects the performance of image retrieval system. The commonly used visual features are image spatial layout, color, texture and shape. Image feature space is combined to achieve the discriminating ability that is not possible to achieve when the features are used separately. Due to this reason, in this paper, we aim to explore the low-level feature combination that are based on color and shape features. We selected color moments and color histogram to represent color while shape is represented by using invariant moments. We selected this combination, as these features are reported intuitive, compact and robust for image representation. We evaluated the performance of our proposed research by using the Corel, Coil and Ground Truth (GT) image datasets. We evaluated the proposed low-level feature fusion by calculating the precision, recall and time required for feature extraction. The precision, recall and feature extraction values obtained from the proposed low-level feature fusion outperforms the existing research of CBIR.

Structural vibration induced by dynamic load or natural vibration is a nonnegligible factor in failure analysis. Based on vibrating boundary condition, impact resistance of shape memory alloy reinforced composites is investigated. In this investigation, modified Hashin’s failure criterion, Brinson’s model and visco-hyperelastic model are implemented into the numerical model to charactering the mechanical behavior of glass fiber/epoxy resin laminates, SMAs and interphase, respectively. First, fixed boundary condition is maintained in simulation to verify the accuracy of material parameters and procedures by comparing with experimental data. Then, a series of vibrating boundaries with different frequencies and amplitudes are applied during the simulation process to reveals the effect on impact resistances. The statistics of absorbed energy and contact force indicate that impact resistance of the composite under high frequency and large amplitude is lower than that under low frequency and small amplitude, and summarized by a mathematical expression.

Low Back Pain (LBP) is one of the most common problems among adults. The usual physiotherapy treatment is to perform physical exercises. However, some LBP patients have false beliefs regarding their pain and they tend to avoid physical movements which might increase their pain and disability. Virtual Reality (VR) has shown to be an effective intervention in improving motor functions and reducing pain perception. Existing VR interventions for LBP rehabilitation were based on a non-immersive VR, whereas to effectively reduce the pain intensity, we need an immersive VR. In this paper, we introduce the development and evaluation of a serious game called RabbitRun with an immersive experience to engage the patients in a virtual environment and distract them from the pain while performing LBP exercises. The initial usability evaluation results suggest that RabbitRun game is enjoyable and acceptable. The game is easy to play and learn and most of the participants are willing to play the game at home. This solution will enhance the rehabilitation outcome since the patients who are suffering from LBP can use the system at their home and train more for long period of time using a smartphone and low-cost virtual reality device such as Google Cardboard.

A study of photovoltaic solar window technologies is reported, focusing on their structural features, functional materials, system development, and suitability for use in practical field applications, e.g. public infrastructures and agricultural installations. Energy generation performance characteristics are summarized and compared to theory-limit predictions. Working examples of pilot-trial solar window-based installations are described. We also report on achieving electric power outputs of about 25 W_p/m² from clear and transparent large-area glass-based solar windows.

Starting from the environmental issues related to global warming, climate change and reduction of greenhouse gas emissions, this review paper describes how CO₂ recycling can represent a challenging strategy suitable to explore new concepts and opportunities for catalytic and industrial development. In this view, the production of dimethyl ether (DME) from catalytic hydrogenation of CO₂ appears as a viable technology, able to meet also the ever-increasing need for alternative environmentally-friendly fuels and energy carriers. Basic considerations on thermodynamic aspects controlling DME production from CO₂ are presented, then summarizing the main catalytic systems developed in such a field. Special attention is paid on the role assumed during last years by zeolite-based systems, either in the methanol-to-DME dehydration step or in the one-pot CO₂-to-DME hydrogenation. On the whole, the productivity of DME results significantly to be dependent on several catalyst features, linked not only to the metal-oxide phase responsible for CO₂ activation/hydrogenation, but also to specific properties of the zeolites (i.e., topology, porosity, surface area, acidity, interaction with active metals, distributions of metal particles, …) influencing activity and stability of hybridized bifunctional heterogeneous catalysts.

To improve carbon efficiency for urban logistics service system composed of a third-party logistics service provider (3PLs) and an e-business enterprise, low-carbon operation game between them was studied. Considering low carbon technology investment cost and sales expansion effect of low carbon level, profit functions for both players were constituted. Based on their different bargaining capabilities, totally 5 types of game scenarios were designed. Through analytical solution, Nash Equilibria under varied scenarios were obtained. By analyzing these equilibria, 4 major propositions were given, in which, some key variables and system performance index were compared. Results show that the best system yields could only be achieved under the fully cooperative situation; limited cooperation only for carbon emission reduction would not benefit the system performance improvement; E-business enterprise-leading game’s performance overtook 3PLs-leading ones.

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

Product introductions play a pivotal role in the success and competitiveness of manufacturing, particularly in the context of new product development. Low-volume manufacturing companies exhibit distinct characteristics that significantly influence the product introduction process. Notably, the quality of information exchange between product design and production interfaces becomes paramount in this high-mix and low-volume industry. Consequently, there exists a pressing need to explore various methods for adapting and customizing management mechanisms and strategies to align with the unique requirements and characteristics of low-volume manufacturing and its associated product introduction processes. While the need for this knowledge is critical in the context of low-volume manufacturing, a majority of existing studies predominantly focus on the management aspects within high-volume manufacturing. Therefore, the primary aim of this study is to investigate the customization of product introduction management strategies to enhance the quality of information content within the realm of low-volume manufacturing. Drawing upon a longitudinal analysis of new product introductions within a low-volume manufacturing company, this study narratively elucidates how the examined company implemented product introduction management strategies to facilitate the enhancement of information content quality during the product introduction phase. The study presents its findings on management strategies across three key stages: pre-implementation, post-implementation, and subsequent modification and refinement of strategies following the initial round of implementation. By shedding light on these strategies, this study offers a comprehensive understanding of management approaches in the context of low-volume product introduction. As a result, it makes a valuable contribution to the discourse on information management and interface management in the high-mix, low-volume manufacturing literature.

To delve into the structure-function relationship of transmembrane proteins (TMPs), robust protocols are needed to produce them in a pure, stable, and functional state. Among all hosts that express heterologous TMPs, E. coli has the lowest cost and fastest turnover. However, many of the expressed in E. coli TMPs are misfolded. Several strategies have been developed to either direct the foreign TMPs to E. coli’s membrane or retain them in a cytosolic soluble form to overcome this deficiency. Here, we summarize protein engineering methods to produce chimera constructs of the desired TMPs fused to either signal peptide or precursor maltose binding protein (pMBP) to direct the entire construct to the periplasm, therefore depositing the fused TMP in the plasma membrane. We further describe strategies to produce TMPs in soluble form by utilizing N-terminally fused MBP without signal peptide. Depending on its N- or C-terminus location, a fusion to apolipoprotein A-I can either direct the TMP to the membrane or shield the hydrophobic regions of the TMP, maintaining the soluble form. Strategies to produce G-protein coupled receptors, TMPs of Mycobacterium tuberculosis, HIV-1 Vpu, and other TMPs are discussed. This knowledge could increase the scope of TMPs’ expression in E. coli.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

The formation and functioning of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, maintenance of genome stability, response to viral infection, apoptosis, and tumor suppression. According to the accepted models, specific interactions, such as SUMO/SIM, formation of disulfide bonds, etc., play a decisive role in the biogenesis of PML bodies. In this work, a number of bioinformatics approaches were used to study proteins found in the proteome of PML-bodies for their tendency to spontaneous liquid-liquid phase separation (LLPS), which is usually caused by weak nonspecific interactions. 205 proteins found in PML bodies have been identified. It has been suggested that UBC9, P53, HIPK2, and SUMO1 can be considered as the scaffold proteins of PML bodies. It was shown that more than half of the proteins in the analyzed proteome are capable of spontaneous LLPS, with 85% of the analyzed proteins being intrinsically disordered proteins (IDPs), and remaining 15% being proteins with intrinsically disordered protein regions (IDPRs). About 44% of all proteins analyzed in this study contain SUMO binding sites and can potentially be SOMYylated. These data suggest that weak nonspecific interactions play a significantly larger role in the formation and biogenesis of PML bodies than previously expected.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.

We are witnessing the severe third outbreak mediated by coronaviruses affecting global public health with unprecedented economic consequences. A better understanding of its phylogenetics, exploration of sequence features and mutational changes could unveil its genealogy to gain insights into the mechanism of transmission and development of possible interventions. Our comparative genomic analyses of >160 isolates of SARS-CoV-2 reveal phylogenetic kinship with other coronaviruses and emergence of evolutionary divergence in clinical isolates. t-SNE-based clustering revealed different clades but no continent specific clusters. Amino acid substitutions at RBD of spike protein provide possible reasons for rapid transmission. Few proteins specific to SARS-CoV-2 were identified which could have implications as therapeutic targets and diagnostic biomarkers. Virtual screening identified repurposed drugs, known nutraceuticals, for specific interventions. These phylogenetic observations reveal the ancestry and computational studies reveal the emergency measures to interject this emerging pathogen that pose threat to whole of mankind.

Protein immobilization for the functionalization of particles is used in various applications, including biosensors, lateral-flow immunoassays (LFIA), bead-based assays, and others. Common methods for the quantification of bound protein are measuring protein in the supernatant before and after coating and calculating the difference. This popular approach has the potential for a significant overestimation of the amount of immobilized protein since layers not directly bound to the surface (soft protein corona) are usually lost during washing and handling. Only the layer directly bound to the surface (hard corona) can be used in subsequent assays. A simplified amino acid analysis method based on acidic hydrolysis and RP-HPLC-FLD of tyrosine and phenylalanine (aromatic amino acid analysis, AAAA) is proposed to directly quantify protein bound to the surface of gold nano- and latex microparticles. The results are compared with indirect methods such as colorimetric protein assays, such as Bradford, bicinchoninic acid (BCA), as well as AAAA of the supernatant. For both particle types, these indirect quantification techniques show a protein overestimation of up to 1700% compared to the direct AAAA measurements. In addition, protein coating on latex particles was performed both passively through adsorption and covalently through EDC/sulfo-NHS chemistry. Our results showed no difference between the immobilization methodologies. This finding suggests that usual protein determination methods are no unambiguous proof of a covalent conjugation on particles or beads.

L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compare activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimised and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the ‘in-gel’ staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria.

Background: C-reactive protein (CRP) is a predictive biomarker of colorectal surgery (CRS) complications but has not been evaluated by comparing patients undergoing CRS with intracorporeal anastomosis (IA) or extracorporeal anastomosis (EA). Therefore, we aimed to describe postoperative CRP values between two groups of patients who underwent laparoscopic right hemicolectomy for right-side colon cancer with IA or EA. Methods: We retrospectively reviewed the data of patients affected by right-side colon cancers who underwent laparoscopic right-hemicolectomy with ileo-colic IA or EA between January 2016 and December 2022. Results: A total of 340 patients underwent laparoscopic right hemicolectomy. EA was performed in 238 (70%) and IA in 102 (30%) cases. Patients with IA showed significantly higher values of CRP in the second, third and fourth postoperative days (15.2 mg/dL vs 9.5 mg/dL p=

The members within the genus Thermoanerobacter have been much less investigated for protein and amino acid metabolism as compared with carbohydrates. The present study investigates the biotechnological potential of Thermoanaerobacter mathranii (DSM 11426) concerning its ability to produce high energy alcohols from amino and fatty acids. End-product formation was analyzed from glucose in the presence and absence of butyric acid as well as from selected proteins, and all amino acids. T. mathranii did not degrade any of the proteins tested to a large extent but de-grade several amino acids, namely serine and the branched-chain amino acids (leucine, isoleu-cine, valine) when cultivated in the presence of thiosulfate. The main end products from the branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols. 13C2-labeled leucine revealed that the strains degraded the amino acid in the pres-ence of thiosulfate, producing 3-methyl-1-butyrate, which was then used as an electron acceptor which led to the accumulation of 3-methyl-1-butanol. The strain is highly ethanologenic, pro-ducing more than 1.2 mol ethanol per mol of glucose degraded. The strain was able to reduce volatile fatty acids during glucose fermentation to their corresponding alcohol, further suggest-ing this strain may be of greater biotechnological value beyond bioethanol production.

Yaba monkey tumor virus (YMTV) and Tanapox virus (TPV) are members of the Yatapoxvirus genus and can infect humans and other primates. Despite the threat posed by yatapoxviruses, the factors determining their host range are poorly understood. In this study, we analyzed the ability of YMTV and TPV orthologs of vaccinia virus K3 (called 012 in YMTV and TPV), which share 75% amino acid identity with one another, to inhibit PKR from 15 different primate species. We first used a luciferase-based reporter, and found that YMTV and TPV K3 orthologs inhibited PKR in a species-specific manner and showed distinct PKR inhibition profiles. TPV 012 inhibited PKR from 11 primates, including human, substantially better than YMTV 012. In contrast, both K3 orthologs inhibited the other four primate PKRs comparably well. Using YMTV 012 and TPV 012 hybrids, we mapped the region responsible for the differential PKR inhibition to the C- terminus of the K3 orthologs. Next, we generated chimeric vaccinia virus strains to investigate whether TPV K3 and YMTV K3 orthologs could rescue replication of a vaccinia virus strain that lacks PKR inhibitors K3L and E3L. Virus replication in primate-derived cells generally correlated with the patterns observed in the luciferase-based assay. Together, these observations demonstrate that yatapoxvirus K3 orthologs have distinct PKR inhibition profiles and inhibit PKR in a species-specific manner, which may contribute to the differential susceptibility of primate species to yatapoxvirus infections.

Expression of the breast cancer resistance protein (BCRP/ ABCG2) transporter is downregulated in placentas from women with preeclampsia (PE) and in an immunological rat model of PE, which closely resembles human PE. While many drugs are substrates of this important efflux transporter, the impact of BCRP downregulation on maternal and fetal drug exposure has not been investigated. Using the PE rat model, we performed a pharmacokinetic study with rosuvastatin (RSV), a BCRP substrate, to investigate this impact. PE was induced in rats during gestational days (GD) 13 to 16 with daily low-dose endotoxin. On GD18, RSV (3 mg/kg) was administrated intravenously, and rats were sacrificed at time intervals between 0.5-6 hours. Placental expression of Bcrp and Oatp2b1 significantly decreased in PE rats. A corresponding increase in RSV levels was seen in fetal tissues and amniotic fluid of the PE group (p&lt;0.05), while maternal plasma concentrations remained unchanged. An increase in Bcrp expression and decreased RSV concentration, was seen in the livers of PE dams. This suggests that PE-mediated transporter dysregulation leads to significant changes in the maternal and fetal RSV disposition. Overall, our findings demonstrate that altered placental expression of transporters in PE can increase fetal accumulation of their substrates.

Whey protein was pretreated with multi-frequency ultrasound in mono, dual, and tri-frequency modes. The effect of multi-frequency ultrasound pretreatment on the hardness, chemical forces, and microstructure of acid-induced whey protein gel was investigated. Whey protein gels pretreated with dual and tri-frequency ultrasound showed higher hardness (p3.35 mm) in those samples were resisted to gastric digestion. Moreover, the tri-frequency ultrasound pretreatment of whey protein gel released the least free amino group during gastric digestion. In contrast, whey protein gel with the mono-frequency ultrasound pretreatment released the highest amount of free amino acid group during intestinal digestion. Findings from this study suggested that gel hardness and network density could modulate the digestion behaviors of protein gels.

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.

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.

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.

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.

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.

Biotechnological potential of Thermoanaerobacter strain AK15 to produce ethanol and valuable alcohols from carbohydrates and amino acids were evaluated in present study. The strain is highly ethanologenic, producing a maximum of 1.57 mol ethanol per mol of glucose degraded at high liquid-gas phase ratios. The strain degrades most of the sugars tested as well as starch and pretreated hydrolysates of biopolymers (Whatman paper, newspaper, Timothy grass, Rhubarb leaves, and several macroalgae species) to ethanol mainly. The strains degraded serine and threonine when used as a single substrate, producing mainly acetate and ethanol as end products, and the branched-chain amino acids (leucine, isoleucine, valine) when cultivated in the presence of thiosulfate. The main end products from branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols. Finally, the strain was also shown to use butyrate as an electron sink during glucose degradation resulting in the reduced product butanol in addition to end products produced from glucose. Thus, strain AK15 is a promising candidate for ethanol and fine chemical production from a range of lignocellulosic and algal biomass.

Developing prolonged antigen delivery systems that mimick the long-term exposure to pathogens appears as a promising, still poorly explored approach to reach durable immunities. In this study, we have used a simple technology by which his-tagged proteins can be assembled, assisted by divalent cations, as supramolecular complexes with progressive complexity, namely protein-only nanoparticles and microparticles. Microparticles produced out of nanoparticles are biomimetics of secretory granules from the mammalian hormonal system. Upon subcutaneous administration, they slowly disintegrate, acting as an endocrine-like secretory system, and rendering the building block nanoparticles progressively bioavailable. The performance of such materials, previously validated for drug delivery in oncology, has been tested here regarding the potential for time-prolonged antigen release. This has been done by taking, as building blocks, a nanostructured version of p30, a main structural immunogen from the African swine fever virus (ASFV). By challenging the system in both mice and pigs, we have observed unusually potent pro-inflammatory activity in porcine macrophages, and long-lasting humoral and cellular responses in vivo, which might overcome the need for an adjuvant. The robustness of both innate and adaptive responses tag, for the first time, these dynamic depot materials as a novel and valuable instrument with transversal applicability in immune stimulation and vaccinology.

: F-box proteins are a large gene family in plants, and play crucial roles in plant growth, development, and stress response. However, a comprehensive investigation of F-box family genes in cultivated peanut (Arachis hypogaea L.), has not been undertaken. In this study, we used a bioinformatics approach to identify and analyze F-box protein family genes in the cultivated peanut genome, and examined their expression profiles. Herein, a total of 95 F-box protein family members on 18 chromosomes were identified in cultivated peanut, which were sequentially designed as AhFBX1-AhFBX95. Phylogenetic analysis classified these AhFBXs into four different groups (Group I - IV), and eight subfamilies based on the structural domains of the C-terminal. Structural analysis revealed the presence of ten unique motifs within these genes. Additionally, the investigation of non-synonymous and synonymous substitution rates (Ka/Ks), and synteny in the F-box proteins, provided valuable insights into the evolutionary and domestication processes of AhFBX genes in peanut. Furthermore, in silico expression profiling of 22 different tissues demonstrated that most genes were predominantly expressed in leaves, pistils, and the aerial gynophore tip, while some members showed tissue-specific expression at the apex of both vegetative and reproductive shoots. Subsequently, we validated the expression of 9 differentially expressed genes (DEGs) using transcriptomeic data of lateral branch development and qRT-PCR analysis. These DEGs may be involved in regulating the development of lateral branches and subsequently affect the architecture of peanut plants.

The persistent threat of cancer remains a significant hurdle for global health, prompting the exploration of innovative approaches in the quest for successful therapeutic interventions. Cyclin-dependent kinase 9 (CDK9), a central player in transcription regulation and cell cycle progression, has emerged as a promising target to combat cancer. Its pivotal role in oncogenic pathways and the pressing need for novel cancer treatments has propelled CDK9 into the spotlight of drug discovery efforts. This article presents a comprehensive study that connects a multidisciplinary approach, combining computational methodologies, experimental validation, and the transformative PROTAC (Proteolysis-Targeting Chimera) technology. By uniting these diverse techniques, we aim to identify, characterize, and optimize a new class of degraders targeting CDK9. We explore these compounds for kinase inhibitory properties and potential to induce targeted protein degradation, offering a novel and potentially more sustainable approach to cancer therapy. This cohesive strategy expresses the interface between computational predictions and experimental insights, with the ultimate goal of advancing the development of effective anticancer therapeutics targeting CDK9.

Background: Eukaryotes whole-genome sequencing is crucial for species identification, gene detection and protein-annotation. Oxford Nanopore sequencing serves as an affordable and rapid platform for sequencing eukaryotes, however the relatively higher error rates require computational and bioinformatic efforts to produce more accurate genome assemblies. Here, we evaluated the effect of read correction tools on eukaryotes genome completeness, gene detection and protein-annotation. Methods: Reads generated by ONT of four eukaryotes, C. albicans, C. gattii, S. cerevisiae, and P. falciparum, were assembled using minimap2 and underwent three rounds of read correction using flye, medaka and racon. The generates consensus FASTA files were compared for total length (bp), genome completeness, gene detection, and protein-annotation by QUAST, BUSCO, BRAKER1 and InterProScan, respectively. Results: genome completeness was dependent on assembly method rather than read correction tool, however, medaka performed better than flye and racon. Racon significantly performed better than flye and medaka in gene detection, while both racon and medaka significantly performed better than flye in protein-annotation. Conclusion: We show that three rounds of read correction significantly affects gene detection and protein-annotation which are dependent on assembly quality in preference to assembly completeness.

Background and Objectives: Obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis resistant obese individuals. Materials and Methods: Thirty-nine, periodontally healthy subjects were enrolled. Based on BMI scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were assessed for interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A) and CRP. Results: GCF CRP levels were significantly higher in obese than lean individuals. No statistically significant differences were noted between the two groups in both GCF and blood on any of the inflammatory cytokine levels. IL-17A was not detected in GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, the association tended to be stronger in obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels positively associated with multiple GCF inflammatory cytokines (e.g., IL-1β, IL-6, IL-8 and TNF-α) in all subjects, the associations tended to be weaker in obese individuals (e.g., IL-1β, IL-6, TNF-α). Furthermore, the levels of GCF inflammatory cytokines IL-6 and TNF-α were depressed in obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a dysregulated inflammatory cytokine response in the gingival tissues of obese individuals.

Repeated cocaine produces an enhanced locomotor response (sensitization) paralleled by biological adaptations in the brain. Previous studies demonstrated region-specific responsiv-ity of adenosine monophosphate-activated protein kinase (AMPK) to repeated cocaine. AMPK maintains cellular energy homeostasis at the organismal and cellular level. Here we first quanti-fied changes in phosphorylated (active) and total AMPK in the cytosol and synaptosome of the medial prefrontal cortex, nucleus accumbens, and dorsal striatum following acute or sensitizing cocaine injections. Rats were given cocaine (15 mg/kg, IP) or saline for six days with a challenge injection on day seven resulting in four groups: saline-saline, saline-cocaine, cocaine-saline, and cocaine-cocaine. Brain region and cellular compartment selective changes in AMPK and pAMPK were found with some differences associated with acute withdrawal versus ongoing cocaine treatment. Other rats were pretreated with the indirect AMPK activator metformin. Metformin potentiated the locomotor activating effects of acute cocaine but blocked the development of sensi-tization. Sex differences largely obscured protein level treatment group effects, although pAMPK in the NAc shell cytosol was surprisingly reduced by metformin in rats receiving repeated co-caine. These data inform our understanding of AMPK activation dynamics in subcellular com-partments and provide additional support for repurposing metformin for cocaine use disorder.

CagY is the largest and most complex protein from Helicobacter pylori's type IV secretion system (T4SS) and may participate in the modulation of gastric tissue inflammation. A three-dimensional structure has been reported for only two segments of the protein. To build a more complete model, particularly the region that spans between the outer membrane (OM) and the inner membrane (IM), we employed different approaches, including homology modeling, ab initio, and deep learning techniques. For the long-middle repeat region (MRR), modeling was performed using deep learning techniques and Molecular Dynamics. The modeled segments were assembled into a chain of 1595 aa, and a 14-chain CagY multimer structure was composed by structural alignment. The final multimer structure correlated with previously published struc-tures and allows to show how the multimer may form the T4SS channel through which CagA and other molecules are translocated to gastric epithelial cells. The model further confirmed that MRR, the most polymorphic and complex region of CagY, presents numerous cysteine residues forming disulfide bonds that stabilize the protein and suggest this domain probably functions as a contractile region that may play an essential role in the modulatory activity of CagY on tissue inflammation.

Eimeria tenella rhoptry protein has the properties of a protective antigen. EtROP27 is a pathogenic related gene detected by transcriptome, but its expression pattern, immunogenicity and potency have been unknown. Therefore, a gene segment of EtROP27 was amplified and transplanted to pET28a prokaryotic vector for recombinant protein expression and purified to generate polyclonal antibody. Then, RT-PCR, Western blotting were performed to know the expression pattern of EtROP27. Subsequently, animal experiments were conducted to evaluate the immunoprotective effect of the recombinant protein using different immunizing doses (50, 100, 150 μg). The results showed that the expression of EtROP27 gradually increased with the prolongation of infection time, reaching the highest level after 96 hours and then decreased. And EtROP27 was a natural antigen of coccidia which can stimulate the body to produce high levels of IgY. As recombinant protein vaccines, the immune protection evaluation tests of EtROP27 showed that the average weight gain rate of the immune challenge groups were significantly higher than that of the infection control group. The average lesion scores were significantly lower than that of the control group. The oocyst excretion decreased by 81.25%, 86.21%, 80.01% and the anticoccidial index were 159.45, 171.47, 166.75. EtROP27 is a promising candidate antigen gene for development of coccidiosis vaccine.

The MLL1 gene located on chromosome 11q23, is crucial for histone lysine-specific methylation and is frequently implicated in various leukemia types. Despite prior in silico investigations into non-synonymous single nucleotide polymorphisms (nsSNPs) associated with leukemia in the MLL1 gene, there is a dearth of comprehensive studies evaluating their impact on the protein's structure, function, and post-translational modifications. Addressing this, our study screened 2049 nsSNPs from the dbSNP database, identifying 62 high-risk variants. A thorough domain analysis revealed that these nsSNPs are distributed across seven domains of the MLL1 protein, potentially affecting their functions. Our conservation analysis highlighted 31 nsSNPs as deleterious, suggesting their potential effects on protein stability and function. Furthermore, utilizing the MutPred2 tool, we identified mutations affecting metal-binding, protein loop structures, and post-translational modifications, which could alter the MLL1 protein's native functionality. Interaction network analysis underscored the role of MLL1 in hematopoietic cell development, implying that mutations may influence hematological malignancies. Additionally, a subset of non-coding SNPs was found to possess regulatory capabilities, potentially affecting gene expression and chromatin modification. Most significantly, using CScape and CScape-somatic tools, four nsSNPs were predicted to be oncogenic, with two classified as cancer drivers, underscoring their potential role in leukemia development. The oncogenic nsSNP, D2724G, located between the FY-rich N and FY-rich C domain of the MLL1 protein, has raised significant interest due to its potential impact on proteolytic cleavage. Predictive analyses, such as those by Mutpred2, suggest a loss of cleavage at D2724 caused by this mutation, potentially affecting the formation of essential MLL1 fragments, p320 and p180. These fragments play a crucial role in creating a stable multiprotein complex that localizes to a specific subnuclear region. Therefore, mutations like D2724G can potentially alter gene expression patterns, influencing cellular behavior and possibly fostering a cancer-prone environment. In conclusion, our research provides an in-depth assessment of the effects of nsSNPs in the MLL1 gene on leukemia, offering potential avenues for personalized treatment strategies, early detection, prognosis, and a better understanding of hematological malignancy genesis.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.

(1) Background: Vitamin K deficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and increased risk of vascular calcifications. A method to indirectly measure Vitamin K status is measuring the blood level of Vitamin K dependent proteins (VKDP)- osteocalcin (OC) and matrix GLA protein (MGP). The aim of this study is to correlate the level of OC and MGP with markers of CKD mineral bone disorder (CKD-MBD). (2) Methods: We conducted a single-center cross-sectional study that included 45 CKD G5D patients and measured blood biochemistry, complete blood count and intact osteocalcin and matrix GLA protein. (3) Results: We found a strong statistically significant correlation of OC with the markers of CKD-MBD such as: iPTH , serum calcium and serum phosphorus and a strong indirect statistically significant correlation with abdominal circumference. There was also a statistically significant correlation of MGP with markers of inflammation (CRP). Higher levels of MGP were found in patients treated with vitamin K antagonists, non-calcium based phosphate binders and vitamin D receptor activator- paricalcitol. (4) Conclusions: In our study, we found that vitamin K deficiency, measured indirectly using the level of VKDP is associated to CKD-MBD. The use of medication such as phosphate binders, that reduce vitamin K absorbtion, Vitamin D that increases Vitamin K requirements and also vitamin K antagonists, seem to have an influence on the blood level of VKDPs.

Autophagy is a highly conserved catabolic process in eukaryotic cells. Reactive nitrogen species play roles as inductors and signaling molecules of autophagy. A key mechanism of NO-mediated signaling is S-nitrosylation, a posttranslational modification (PTM) of proteins at cysteine resi-dues. In the present work we analyzed the patterns of protein S-nitrosylation during the induc-tion of autophagy in Triticum aestivum roots. The accumulation of S-nitrosylated proteins in the cells during autophagy induced by KNO2 and antimycin A was visualized using monoclonal an-tibodies by Western blot analysis, and proteins were identified using a standard bottom-up pro-teomics approach. Protein S-nitrosylation is a labile and reversible PTM, and therefore SNO group can be lost during experimental procedures. Subsequent bioinformatic analysis using predictive algorithms and protein-ligand docking showed that identified proteins possess hypothetical S-nitrosylation sites. Analyzing protein-protein interaction networks enabled us to discover the targets that can directly interact with autophagic proteins, and those that can interact with them indirectly via key multifunctional regulatory proteins. In this study, we show that S-nitrosylation is a key mechanism of NO-mediated regulation of autophagy in wheat roots. A combination of in silico predictive algorithms with a mass spectrometry analysis provides a targeted approach for the identification of S-nitrosylated proteins.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

In this study, we reported that novel single-chain fusion-proteins linked thromboxane A2 (TXA2) receptor (TP) to a selected G-protein α-subunit q (SC-TP-Gαq), or s (SC-TP-Gαs) could be stably expressed in megakaryocytes (MK). We tested the MK-released platelet-linked particles (PLPs) to be used as a vehicle to deliver the over-expressed SC-TP-Gαq), or s (SC-TP-Gαs) to regulate human platelet function. To understand how the single-chain TP-Gα fusion proteins could regulate opposite platelet activities by an identical ligand TXA2, we used dual-binding domains linked to different signaling pathways within a single polypeptide chain using a 3D structural model. The immature MKs were cultured and transfected with cDNAs constructed from structural models of the individual SC-TP-Gαq and SC-TP-Gαs, respectively. After transient expression was identified, the immature MKs stably expressing SC-TP-Gαq or SC-TP-Gαs (stable cell lines) were selected. The stable cell lines were induced into mature MKs which released PLPs. Western blot analysis confirmed that the released PLPs were carrying the recombinant SC-TP-Gαq or SC-TP-Gαs. Flow cytometry analysis showed the PLPs carrying SC-TP-Gαq were able to perform the activity by promoting platelet aggregation. In contrast, PLPs carrying SC-TP-Gαs reversed Gq to Gs signaling to inhibit platelet aggregation. This is the first time demonstrating that SC-TP-Gαq and SC-TP-Gαs were successfully overexpressed in MK cells and released as PLPs with proper folding. This bio-engineering led to the formation of two sets of biologically active PLP forms, which mediate calcium and cAMP signaling, respectively. As a result, these PLPs are able to bind to identical endogenous TXA2 with opposite activities, inhibiting and promoting platelet aggregation as required for therapeutic process.The results also demonstrated the nucleus-free PLPs could be used to deliver recombinant membrane-bound GPCRs to regulate cellular activity in general.

Kiwifruit is a perennial horticultural crop species with high nutritional and economic value. However, various pathogens stress brings a serious threat to kiwifruit. Pentatricopeptide repeat proteins (PPRs) are characterized by tandem repetitions of 35 amino acid motifs, and have been found to function in plant RNA editing. However, the roles of PPRs in plant development and disease resistance remain unclear. In this study, we performed a genome-wide identification and characterization of PPR gene family in two kiwifruit species (Actinidia chinensis (Ach), and Actinidia eriantha (Ace)) with markedly different disease resistance. A total of 497 and 499 PPRs were identified in Ach and Ace, respectively. All the kiwifruit PPRs could be phylogenetically divided into four subfamilies. There were about 40.68% PPRs predicted to be localized to mitochondria or chloroplasts. Synteny analysis showed that the expansion of kiwifruit PPRs mainly came from segmental duplication. Based on RNA-seq data from the fruit during 12 periods of development and maturity, weighted correlation network analysis suggested that two PPRs Actinidia20495.t1 and Actinidia15159.t1 were involved in the fruit development and maturation. In addition, we observed different gene expression of PPRs and chloroplast RNA editing profiles between resistant and susceptible kiwifruits after pathogen infection, indicating the roles of PPRs in stress response by modulating the editing extend of mRNA. The differentially expressed upstream transcription factors of PPRs were further identified, they may regulate resistance adaption by modulating the PPRs expression. These results provide a solid foundation for further analyses of the functions and molecular evolution of PPRs, in particular, for clarifying the resistance mechanisms in kiwifruits and breeding new cultivars with high resistance.

We successfully created a composite photonic structure out of porous silicon (PSi) microcavities doped by the photochromic protein, photoactive yellow protein (PYP). Massive incorporation of the protein molecules into the pores was substantiated by a 30-nm shift of the resonance dip upon functionalization, and light-induced reflectance changes of the device due to the protein photocycle were recorded. Model calculations for the photonic properties of the device were consistent with earlier results on the nonlinear optical properties of the protein, whose degree of incorporation into the PSi structure was also estimated. The successful proof-of-concept results are discussed in light of possible practical applications in the future.

We advance the notion that much, like artificial nanoparticles, relatively more complex biological entities with nanometric dimensions such as pathogens (viruses, bacteria and other microorganisms) may also acquire a biomolecular corona, upon entering the blood circulation of an organism. We view this biomolecular corona as a component of a much broader non-cellular blood interactome that can be highly specific to the organism, akin to components of the innate immune response to an invading pathogen. We review published supporting data and generalize these notions from artificial nanoparticles to viruses and bacteria. Characterization of the non-cellular blood interactome of an organism may help explain apparent differences in the susceptibility to pathogens among individuals. The non-cellular blood interactome is a candidate therapeutic target to treat infectious and non-infectious conditions.

Recent studies have been able to detect α-synuclein (αSyn) seeding in formaldehyde-fixed paraffin-embedded (FFPE) tissues from patients with synucleinopathies using seed amplification assays (SAAs), but with relatively low sensitivity due to limited protein extraction efficiency. With the aim of introducing an alternative option to frozen tissues, we developed a streamlined protein extraction protocol for evaluating disease-specific seeding in FFPE human brain. We evaluated the protein extraction efficiency of different tissue preparations, deparaffinizations, and protein extraction buffers using formaldehyde-fixed and FFPE tissue of a single Lewy body disease (LBD) subject. Alternatively, we incorporated heat-induced antigen-retrieval and dissociation using a commercially available kit. Our novel protein extraction protocol has been optimized to work with 10 sections of 4.5-µm-thickness or 2-mm-diameter micro-punch of FFPE tissue that can be used to seed SAAs. We demonstrated that extracted proteins from FFPE still preserve seeding potential and further show disease-specific seeding in LBD and multiple system atrophy. To the best of our knowledge, our study is the first to recapitulate disease-specific αSyn seeding behavior in FFPE human brain, with structural validation. Our findings open new perspectives in re-evaluating archived human brain tissue, extending the disease-specific seeding assays to larger cohorts to facilitate molecular subtyping of synucleinopathies.

This study aimed to investigate how transplanting date affects the agronomic and grain quality traits of two early maturing rice varieties. The experiment was conducted in the rice research field of Chungnam Agricultural Research and Extension Services, South Korea and rice materials were transplanted at intervals of approximately 15 days from April 16 to July 16 in 2019 and 2020. Results showed that agronomic and grain quality traits varied according to the transplanting date, and earlier transplanting resulted in the longer period of days from transplanting to heading (DTH). The spikelet number m-2 was highly correlated with the milled rice yield (r = 0.963** for Jinbuol, r = 0.909** for Yeoreumi) and it significantly decreased as the transplanting date was delayed, which was leading to lower yield. Environmental factors, the mean temperature during the grain filling stage, had a negative correlation with head rice rate (r2 = 0.825** for Jinbuol, r2 = 0.803** for Yeoreumi), and the number of days from transplanting to heading showed negative correlation with protein content (r2 = 0.777** for Jinbuol, r2 = 0.833** for Yeoreumi). Therefore, increasing the number of days from transplanting to heading date can lead to higher milled rice yield and lower protein content, and avoiding heading dates on July 17 can improve the appearance traits. As a results, it is suggested that early transplanting is advantageous to increase the milled rice yield and grain quality of early maturing rice.

Novel treatment strategies are emerging for rare, genetic diseases, resulting in clinical trials that require adequate biomarkers for the assessment of the treatment effect. For enzyme defects, biomarkers that can be assessed from patient serum, such as enzyme activity, are highly useful, but the activity assays need to be properly validated to ensure a precise, quantitative measurement. Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by the deficiency of the lysosomal hydrolase aspartylglucosaminidase (AGA). We have here established and validated a fluorometric AGA activity assay for human serum samples from healthy volunteers and AGU patients. We show that the validated AGA activity assay is suitable for the assessment of AGA activity in the serum of healthy controls and AGU patients, and it can be used for diagnostics of AGU and, potentially, for following a treatment effect.

The flexitarian diet, which emphasizes a reduction in meat consumption, has been identified as a crucial factor in transitioning to sustainable food systems that can help combat climate change and improve food and nutritional security, particularly in areas where food choices are abundant. Despite Brazil being a major meat producer, meat consumption among Brazilians has been decreasing in recent years, with a growing portion of the population adopting meat-free and meat-reduced dietary models. In this study, we conducted the first non-industry funded scientific investigation of Brazilian flexitarians, with the goal of characterizing their socio-economic and demographic characteristics, motivations for adopting flexitarianism, frequency of animal-based meat consumption, and main substitutes consumed. Data was collected from 1029 self-identified flexitarians in Brazil. Our findings indicate that the flexitarian food model is primarily adopted by women and is motivated by concerns about the environmental impact of meat consumption, personal health, and animal welfare. Flexitarians were found to have a consumption profile that can be divided into three groups: low (consuming meat 36 times a week), medium (consuming meat 7 times a week), and high (consuming meat 4 times a week). The flexitarian meals pattern is characterized by lower consumption of beef (less than 2 times per week) and higher consumption of chicken (3 times per week) and is supplemented by plant-based protein sources and eggs as the main meat substitutes.