Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused bundling of actin filaments in the absence of alpha-actinin and enhanced alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La stabilized the two proteins on actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

In recent years there has been an increasing interest in developing novel materials based on natural biopolymers as a renewable alternative of petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study we propose the use of rapeseed protein-rich meal as main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewable origin. Application as sustainable products in the present high-tech society needs modification of basic native properties of these natural compounds. The original route proposed in this paper consists in the preparation via compression moulding of flexible biomaterials stabilized by crosslinkers/chain extenders. Investigation of the effects of different denaturing and disulfide bond reducing agents, crosslinkers, and preparation conditions on the material mechanical behaviour demonstrated that the novel materials have appreciable strength and stiffness. The results show the potential of utilizing full meal from vegetable by-products to prepare protein-based materials with granted ecofriendly characteristics and mechanical properties adequate to specific structural applications.

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associate with the use of small molecule antibiotics and AMPs is the combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review is intended to cover and critically analyze the design, synthetic strategies, antibacterial activity and, when possible, the cytotoxicity of antibiotic-AMPs conjugates.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Self-assembling peptide P11-4 is amphiphilic and pH-triggered with demonstrated effectivity repairing early carious lesions in enamel. However, P11-4 effects on dentin biomineralization and repair remain unexplored. Thus, cytocompatibility and effectiveness of P11-4 inducing mineralization and migration of odontoblast-like cells (MDPC-23) were investigated. MDPC-23 were seeded in contact with P11-4(0.5µg/ml and 1µg/ml), Dentin Matrix Protein 1 (DMP1 0.5µg/ml and 1 µg/ml) or Calcium hydroxide (Ca(OH)2 100µg/ml) solutions. Cytotoxicity was verified using MTT (n=6/group). Mineralization was tested using Alizarin Red (n=4/group). Cell migration was assessed by light microscopy (n=2/group). MTT and Alizarin Red data were compared using Krus-kal-Wallis and Mann-Whitney (α=0.05). P11-4 (0.5µg/ml and 1µg/ml) and DMP1 (0.5µg/ml and 1µg/ml) presented the highest cytocompatibility; Ca(OH)2 presented the lowest. DMP1 1µg/ml exhibited the highest mineralization ability, with no difference to P11-4 1µg/ml. Ca(OH)2 presented lower values than DMP1 1µg/ml (p<0.05), but similar to P11-4 1µg/ml. P11-4 and DMP1 at 0.5 µg/ml showed induced less mineralization than P11-4 and DMP1 at 1µg/ml (p<0.05), with no difference to Ca(OH)2. All materials stimulated cell migration, however, lower concentrations of DMP1 and P11-4 provided better results. P11-4 is cytocompatible, induces mineralization and MDPC-23 migration like DMP1. P11-4 could be an alternative for dentin mineralization and tooth repair.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

Semantic image segmentation has recently witnessed considerable progress by training deep convolutional neural networks (CNNs). The core issue of this technique is the limited capacity of CNNs to depict visual objects. Existing approaches tend to utilize approximate inference in a discrete domain or additional aides and do not have a global optimum guarantee. We propose the use of the multi-label manifold ranking (MR) method in solving the linear objective energy function in a continuous domain to delineate visual objects and solve these problems. We present a novel embedded single stream optimization method based on the manifold ranking (MR) model to avoid approximations without sacrificing expressive power. In addition, we propose a novel network, which we refer to as dual multi-scale manifold ranking (\textbf{DMSMR}) network, that combines the dilated, multi-scale strategies with the single stream MR optimization method in the deep learning architecture to further improve the performance. Experiments on high resolution images, including close-range and remote sensing datasets, demonstrate that the proposed approach can achieve competitive accuracy without additional aides in an end-to-end manner.

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties putting them on a new path in medicine. Their conformational rigidity that improves proteolytic stability, leads to rapid penetration into tissues via any possible route of administration and elimination, occurring by renal metabolism, is of great importance for people with a history of liver diseases. In addition, each ring can function independently, making them extremely versatile molecules for further optimization. In this paper we compared the potentiometric and spectroscopic properties studied by UV-Vis, MCD, and EPR, of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH). In particular we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts, with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively, and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2).

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

We have identified a new human voltage-gated potassium channel (hKv1.3) blocker, NnK-1, in the jellyfish Nemopilema nomurai, based on its genomic information. The gene sequence encoding NnK-1 contains 5,408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids, containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the chemically synthesized fifth peptide, NnK-1, is an effective hKv1.3 blocker. A multiple sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that four residues (3Asp, 25Lys, 33Lys, and 34Thr) of NnK-1, together with six cysteine residues, are conserved. Therefore, we hypothesize that these four residues are crucial for the binding of the toxins to voltage-gated potassium channels.

In the context of type 2 diabetes (T2DM), fasting and postprandial hyperglucagonemia have long been linked to the disease's development and progression. However, recent studies have brought to light the positive impact of glucagon-agonists on lipid metabolism and energy homeostasis. This review delves into the intricate relationship and underlying mechanisms between glucagon and nutrient composition, which may hold promise in devising novel therapeutic approaches for T2DM management.

To date, viruses closely related to SARS-CoV-2 have been reported in four bat species: Rhinolophus acuminatus, Rhinolophus affinis, Rhinolophus malayanus, and Rhinolophus shameli. Here, we analysed 343 sequences of the mitochondrial cytochrome c oxidase subunit 1 gene (CO1) from georeferenced bats of the four Rhinolophus species identified as reservoirs of SARS-CoV-2-like viruses. Haplotype networks were constructed in order to investigate patterns of genetic diversity among bat populations of Southeast Asia. No strong geographic structure was found for the four Rhinolophus species, suggesting high dispersal capacity. The ecological niche of SARS-CoV-2 like viruses was predicted using the four localities of bat SARS-CoV-2-like viruses and the localities where bats showed identical or very similar CO1 haplotypes than virus-positive bats. The ecological niche of SARS-CoV-like viruses was deduced from the localities where bat SARS-CoV-like viruses were previously detected. The results show that the ecological niche of SARS-CoV2-like viruses includes several regions of mainland Southeast Asia whereas that of SARS-CoV-like viruses is mainly restricted to China. In agreement with these results, human populations in Laos, Vietnam, Cambodia, and Thailand appear to be much less affected by the Covid-19 pandemic than other countries of Southeast Asia. In the climatic transitional zone between the two ecological niches (southern Yunnan, northern Laos, northern Vietnam, and possibly Hainan and Taiwan), genomic recombination between highly divergent viruses is more likely to occur. Since recombinant viruses can threaten the benefit of vaccination campaigns, these regions should be under surveillance.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus. Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C‑like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.

Fused deposition modeling (FDM) is widely applied in various fields due to its affordability and ease of use. However, it faces challenges such as achieving high surface quality, precise dimensional tolerance and overcoming anisotropic mechanical properties. This paper analyzes and compare the machinability of 3D printed PLA, PETG and carbon fiber reinforced PETG focusing on surface roughness and burr formation. A design of experiments (DoE) with a full factorial design was used, considering three factors: rotation speed, feed rate and depth of cut. Each factor had different levels: rotational speed at 3000, 5500 and 8000 rpm; feed rate at 400, 600 and 800 mm/min; and depth of cut at 0.2, 0.4, 0.6, and 0.8 mm. Machinability was evaluated by roughness and burr height using a profilometer for all the materials under the same milling conditions. To evaluate the statistical significance of the influence of various processing parameters on surface roughness and burr formation in 3D printed components made of three different materials PLA, PETG and carbon fiber reinforced PETG, an analysis of variance (ANOVA) test was conducted. This analysis investigated whether variations in rotational speed, feed rate and depth of cut resulted in measurable and significant differences in machinability results. Results showed that milling parameters significantly affect roughness and burr formation, with optimal conditions for minimizing any misalignment highlighting the trade-offs in parameter selection. These results provide insights into the post-processing of FDM-printed materials with milling, indicating the need for a balanced approach to parameter selection based on application-specific requirements.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. 5 to 10% of recovered patients in Wuhan test positive again; this suggest that for controlling COVID-19, vaccines may be better option than drugs. A clinical trial to evaluate an anti-COVID-19 vaccine has started recently. However, its efficacy and potency have to be evaluated and validated. As an alternative, we are presenting a first-of-its-kind, designed multi-peptide subunit based epitope vaccine against COVID-19. The vaccine construct comprise an adjuvant, CTL, HTL, and B-cell epitopes joined by linkers. The vaccine is non-toxic, non-allergenic, thermostable and immunogenic with the capability to elicit a humoral and cell-mediated immune response. The findings are validated with high-end computation-based methods. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as public health priority.

The 2-Acetyl-1-pyrroline (2-AP) is the most important volatile in determining the aroma of fragrant rice, however, the transcriptional regulation mechanism of 2-AP biosynthesis in fragrant rice is still unclear. In this study, the Osp5cs1 knockout mutant lines and OsP5CS1 over-expression lines were constructed by genetic transformation of indica rice cultivar i.e., ‘Zhonghua11’, which was knocked out OsBADH2 to produce fragrance in aromatic rice. The OsP5CS1 gene was also identified as a key gene in the 2-AP biosynthesis pathway of aromatic rice. The OsP5CS1 promoter was used as bait, and the transcription factor OsbZIP60-like was screened by yeast one-hybrid assays. The transcription factor OsbZIP60-like specifically bound to the OsP5CS1 gene. The dual luciferase reporting system found that OsbZIP60-like transcription factor promoted the transcriptional activation of OsP5CS1. Compared with the wild type, the OsP5CS1 gene expression was significantly down-regulated in Osbzip60-like mutant, and resulted in substantial reduction in 2-AP biosynthesis. Moreover, the OsP5CS1 gene expression was significantly up-regulated in OsbZIP60-like over-expressed plants, and the 2-AP concentrations were also increased whereas the Osbzip60-like mutants were found to be sensitive to Zn deficiency. Overall, the OsbZIP60-like transcription factor promoted the 2-AP accumulation. This study provides a theoretical basis for the transcriptional regulation mechanism of 2-AP biosynthesis and explores the function of OsbZIP transcription factor in fragrant rice.

Urbanization is considered as a main indicator of regional economic development due to its positive effect on promoting industrial development; however, many regions, especially developing countries, are troubled by its negative effect — the aggravating environmental pollution. Many researchers have indicated that rapid urbanization stimulated the expansion of industrial production scale and increased industrial pollutant emissions. However, this judgement contains a grave deficiency in that urbanization not only expands industrial production scales but can also increase industrial labour productivity and change the industrial structure. To modify this deficiency, we first decompose the influence which urbanization impacts on industrial pollutant emissions into the scale effect, the intensive effect and the structure effect by using the Kaya Identity and the LMDI Method; second, we perform an empirical study of the three effects’ impacts by applying the spatial panel model with data from 282 Chinese cities between 2003 and 2013. Our results indicate that (1) there are significant reverse U-shapes between Chinese urbanization rate and its industrial pollutant emissions; (2) the scale effect and the structure effect have aggravated Chinese industrial waste water discharge, sulphur dioxide emissions and soot (dust) emissions, while the intensive effect has generated a decreasing and ameliorative impact on that aggravated trend. The definite relationship between urbanization and industrial pollutant emissions depends on the combined influence of the scale effect, the intensive effect and the structure effect; (3) there are significant spatial autocorrelations of industrial pollutant emissions between Chinese cities, but the spatial spillover effect from other cities does not aggravate local urban industrial pollutant emissions, we offer an explanation to this contradiction that the vast rural areas surrounding Chinese cities have served as sponge belts and have absorbed the spatial spillover of cities’ industrial pollutant emissions. According to the results, we argue that this type of decomposition of the influence into three effects is necessary and meaningful, it establishes a solid foundation for understanding the relationship between urbanization and industrial pollutant emissions, and effectively helps to meet relative policy making.

Background/Objectives: Conventional surgery gland using the naked eye remains the standard for submandibular gland resection. Owing to its excellent automatic focus and high magnification, the ORBEYE 3D system introduces precise submandibular resection with less stress. Therefore, we examined the usefulness of the exoscope in submandibular gland resection for the first time. Methods: This retrospective study enrolled 12 patients who underwent submandibular gland resection using an ORBEYE exoscope at the Department of Head and Neck Surgery and Otorhinolaryngology at Kansai Medical University from April 2021 to March 2024. Surgical outcomes were retrospectively reviewed. Results: The mean age of the 12 patients (six females and six males) was 58.5 years (23–83 years). The final histopathology showed pleomorphic adenoma in eight cases, non-sebaceous-type lymphadenoma and carcinoma ex pleomorphic adenoma in one case each, and sialolithiasis with chronic inflammation in two cases. We performed facial artery and vein sparing in all cases except one in which level I neck dissection, including the submandibular gland, was performed. In all cases, we identified the marginal mandibular branches of the facial, hypoglossal, and lingual nerves, as well as the submandibular duct. No postoperative complications occurred in any patient. The mean operative time was 104 min (80–129 min). The mean blood volume lost was 20 mL (5–43 mL). Conclusions: Using ORBEYE in submandibular gland resection will contribute to preserving the mandibular marginal branch of the facial and lingual nerves and the facial artery and vein, and visualizing the submandibular duct, which are important structures surrounding the submandibular gland.

The general synthesis of boron-containing cyclic compounds (boracycles) necessitates toxic organotin precursors or highly reactive boron halides. Here we report the synthesis of seven- and five-membered boracycles utilizing arylboronic acid pinacol esters (ArBpins) as stable boron sources. Grignard reagents generated from 2,2′-dibromodibenzyl or 2,2′-dibromobiphenyl reacted with ArBpins, where Ar = 9-anthryl (Anth), 2,4,6-trimethylphenyl (Mes), 2,4,6-triisopropylphenyl (Tip), to give 10,11-dihydro-5H-dibenzo[b,f]borepins or dibenzoborole derivatives. This Bpin-based method was successfully applied to a one-shot double boracycle formation, providing a dihydrodibenzoborepin–anthracene–dihydrodibenzoborepin triad molecule in a good yield. The dihydrodibenzoborepin bearing the Anth group was directly converted to the unsaturated borepin by NBS/AIBN. All products were characterized by NMR, HRMS, and in some cases, single-crystal X-ray diffraction analysis. Additionally, the photophysical properties of the products are also reported.

Since the discovery of mitochondrial-derived peptides (MDP), their participation in cellular metabolism is no longer considered as the sole function of the mitochondria, but importance was also attached to its role as a source of protective factors of metabolic stress. These peptides are encoded in the mitochondrial genome and translated into the mitochondria or cytoplasm, to signal within the cell or be released and bind to membrane receptors. The objective of this work was explored and compare the frequency of MT-RNR1 and MT-RNR2 variants in sequences obtained from T2D individuals and control population. 213 different mitochondrial polymorphisms previously reported in the literature associated with T2D and cardiovascular diseases were analyzed. We can found three variants in the MT-RNR1 not related with MOTS-c coding sequence: m.1189T>C (rs28358571), m.1420T>C (rs111033356), and m.1438A>G (rs2001030); and secondly, three polymorphisms associated to MT-RNR2 m.2667T>C (rs878870626) related to humanin, m.1811A>G (rs28358576) in SHPL3 and m.3027T>C (rs199838004) in SHPL6 associated with statistical differences between the T2D and control group. All these findings were previously related to cardiovascular complications in literature and, as far as we know, relating for the first time in diabetic patients.

Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customized biomaterials able to mimic ECM functionalities represent one of the major strategy to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review new strategies and future perspectives of such synthetic cell microenvironment will be highlighted.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy. We designed a synthetic amelogenin peptide (SP) derived from EMD, and have previously investigated the biological function of SP. However, it is unknown whether SP affects odontoblastic differentiation. In the present study, we investigated the effects of SP in odontoblast-like cells, KN-3 cells. KN-3 cells were treated with SP (0, 1, 10, 100, or 1000 ng/mL) and then cultured for 3, 8, 24, or 48 hours, in order to determine the effects of SP on cell proliferation and detect its optimum concentration. To investigate the effect of SP on odontogenic differentiation, KN-3 cells were treated with SP in odontogenic differentiation medium cultured for 3 or 7 days. Odontogenic differentiation was performed by measuring alkaline phosphatase (ALP) activity, the mRNA expression of dentin sialophosphoprotein (DSPP), the formation of calcified nodules, and calcium deposition into the extracellular matrix. The addition of SP significantly promoted KN-3 cell proliferation; a concentration of 100 ng/ml generated the greatest change in cell proliferation. SP also showed increased expression of markers of odontogenic differentiation and mineralization. These results suggest that SP, derived from EMD, could be a potential for applicate to the dental pulp capping.

Glucose is a simple sugar molecule. The sugar molecule is chemically symbolised as C6H12O6. This means that the glucose molecule contains 6 carbon atoms (C), 12 hydrogen atoms (H) and 6 oxygen atoms (O). In human blood, the molecule glucose circulates as blood sugar. Normally after eating or drinking, our body breaks down the sugars in food and uses them to obtain energy for our cells. To do this, our pancreas produces insulin. Insulin "pulls" sugar from the blood and puts it into the cells for use. If someone has diabetes, their pancreas can't produce enough insulin. As a result, the level of glucose in the blood rises. This can lead one to many potential complications, including blindness, disease, nerve damage, amputation, stroke, heart attack and damage to blood vessels etc. In this study, a non-invasive method for monitoring blood glucose has been developed and is therefore easily usable. The device developed can measure the glucose level continuously and eliminates the disadvantages of the invasive system. Near-IR sensors (optical sensors) were used to estimate the concentration of glucose in the blood; these sensors have a wavelength of 940 nm. The sensor is placed on the tip of the finger and the output of the optical sensor is then connected to the microcontroller at the analogue input. Another sensor used, but only to provide more medical information was the heartbeat sensor. After processing and regression analysis, the glucose level is predicted, and data is sent via the Bluetooth network to a developed APP. The results of the implemented device were compared with available invasive methods. The study consists of a hardware platform inserted into an armband and then a small black parallelepiped-shaped box in which the optical sensors are inserted. The hardware consists of a microcontroller, a Near-IR optical sensor, a heartbeat sensor and a Bluetooth module.

Antiviral peptides (AVPs) represent a promising strategy for addressing the global challenge of viral infections and their growing resistance to traditional drugs. Lab-based AVP discovery methods are resource-intensive, highlighting the need for efficient computational alternatives. In this study, we developed five non-trained but supervised Multi-Query Similarity Search Models (MQSSMs) integrated into the StarPep toolbox. Rigorous testing and validation across diverse AVP datasets confirmed the models' robustness and reliability. The top-performing model, M13+, demonstrated impressive results with an accuracy of 0.969 and a Matthew’s correlation coeffi-cient of 0.71. To assess their competitiveness, the top five models were benchmarked against 14 publicly available machine learning and deep learning AVP predictors. The MQSSMs outper-formed these predictors, highlighting their efficiency in terms of resource demand and public ac-cessibility. Another significant achievement of this study is the creation of the most comprehensive dataset of antiviral sequences to date.

Introduction: Hypertension is a serious public health problem in Morocco. The objective of this pilot study was to estimate the salt intake of Moroccan adults by measuring 24-hour urinary sodium excretion. Methods: 132 participants were recruited from the central region of Morocco. Sodium, potassium and creatinine levels were measured using the 24-hour urine samples. Additional data included anthropometric measurements and socio-demographic questionnaire. Results: The daily sodium, potassium and creatinine excretions were 2779.1±1334.9 mg, 1350.0±642.8 mg and 820.3 ± 381.2 mg, respectively. Data analysis revealed that 71.2% of the participants had a daily sodium intake more than 2000 mg (5g of salt) recommended by the WHO. The mean of potassium excretion was 1350.0±642.8 mg /day, this average was lower than 3.51g per day recommended by the WHO. Conclusion: Public health measures to reduce sodium and increase potassium consumption in order to decrease the population’s risk of high blood pressure and heart disease are recommended.

The present study comprises the second part of our previous work that dealt mainly with the phytochemical and physicochemical characterization of green coffee, clove, cinnamon/clove and nutmeg ethanolic extracts of grape origin. In the present study, we focused on producing a discriminating model concerning green coffee, clove, cinnamon, cinnamon and clove, and nutmeg fine powders based on multivariate analysis of variance and supervised learning on data of volatile compounds analysis, carried out with solid phase dynamic extraction in combination with gas chromatography/mass spectrometry. Results showed that 7 volatile compounds namely ethylene, methanol, 3-methylpentane, ethyl acetate, 9-hexadecen-1-ol, toluene, and methyl acetate could differentiate the investigated samples resulting in a 100% classification rate using the cross-validation method of linear discriminant analysis. Results were further confirmed using partial least squares regression analysis. The study contributes to the typification of green coffee, cinnamon, clove, cinnamon and clove and nutmeg, based on selected volatile compounds, and provides further support to the literature by means of possible adulteration given the statistical models developed.

SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.

Despite energy-related financial concerns and the growing demand for sustainability, many energy efficiency measures are not being implemented in industrial practice. There are a number of reasons for this, including a lack of knowledge about energy efficiency potentials and the assessment of energy savings as well as the high workloads of employees. This article describes the systematic development of an expert system, which offers a chance to overcome these obstacles and contribute significantly to increasing the energy efficiency of production machines. The system employs data-driven regression models to identify inefficient parameter settings, calculate achievable energy savings, and prioritize actions based on a fuzzy rule base. Proposed measures are first applied to an analytical real-time simulation model of a production machine to verify that constraints required for the specified product quality are met. This provides the machine operator with the expert means to apply proposed energy efficiency measures to the physical entity. We demonstrate the development and application of the system for a throughput parts cleaning machine in the metalworking industry.

Porcine parvovirus 8 (PPV8), a novel virus in the Parvoviridae family, was first identified in 2022 in lung samples of domestic pigs from China. Retrospective analyses showed that it had been circulating in China since 1998, but no other countries had reported its presence so far. A recent study conducted in South America did not detect any PPV8-positive samples in that region. Here we report the detection of PPV8 in Hungarian and Slovakian pig farms and the estimated prevalence of the virus in Hungary. Altogether 2230 serum, 233 oral fluid, and 115 processing fluid samples were systematically collected from 23 Hungarian and 2 Slovakian pig farms between 2020 and 2023. A real-time quantitative PCR method was developed to detect the viral genome. Our results revealed the presence of PPV8 on 65% of the Hungarian farms and on both Slovakian farms included in our study, marking its first detection in Europe. Oral fluid samples showed the highest positivity rates, reaching up to 100% in some herds. The viral genome was successfully detected in serum and processing fluid samples too, but with significantly lower prevalence rates of 4% and 5%, respectively. Genetic analysis of 11 partial VP2 sequences demonstrated high similarity to the original Chinese strain but with unique amino acid mutations, suggesting possible local evolution of the virus. Our study presents the first scientific evidence of PPV8 infection outside of China and offers a comprehensive assessment of its prevalence in the Hungarian pig population. Further research is required to understand its potential impact on swine health.

The self-assembly is an intriguing process of great importance in general soft matter and thus re-ceives an ever-growing scientific interest. Its most trivial example is the entropy-driven crystalli-zation of hard spheres. Past works have established the similarities and differences in the phase behavior of monomers and chains made of hard spheres. In the present work, inspired by the dif-ference in the melting points of the pure components, we study, through Monte Carlo simulations, the phase behavior of athermal mixtures composed of fully flexible polymers and individual monomers of uniform size. We analyze how the relative number fraction and the packing density affect crystallization and the established ordered morphologies. A synergetic effect is observed in the crystallization leading to synchronous crystallization of the two species. Structural analysis of the resulting ordered morphologies shows perfect mixing and thus no phase separation, which could split the system into polymer-rich and monomer-rich domains. Due to the constraints imposed by chain connectivity, the local environment of the individual spheres is systematically more spherical and more symmetric compared to the one of spheres belonging to chains. In general, increasing polymer content leads to reduction of the degree of crystallinity. According to the present findings, relative concentration is another determining factor to control the phase behavior of hard colloidal systems based on polymers.

Tissue-like phantoms are widely used as a model for mimicking the optical properties of live tissue. This paper presents the results of a diffusion reflection method as well as fluorescence lifetime imaging microscopy measurements of fluorescein-conjugated gold nanorods in solution as well as inserted in solid tissue-imitating phantoms. A lack of consistency between the fluorescence lifetime results of the solutions and the phantoms raises a question about the ability of tissue-like phantoms to maintain the optical properties of inserted contrast agents.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), etiological agent of the novel coronavirus disease 2019 (COVID-19), has spread since December 2019, resulting in massive health and economic crisis worldwide. While efforts to stop the pandemic are crucial, collecting epidemiological data to help manage current and future pandemics will be important. In addition to humans, serological and molecular based studies have demonstrated SARS CoV-2 exposure in several wild, domestic and farmed animals. For examples Shriner and the team showed serologically an exposure of 40% to the white deer living in close proximity to urban centers. Additional reports have also emerged of susceptibility of animal’s species like cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters to SARS-CoV-2 infection.. It’s worth emphasizing that these reports are based on experimental data mostly derived from Europe, USA, South America and parts of Asia. In limited instances natural infections of SARS-CoV-2 have been reported in pet dogs, cats, tigers, lions, snow leopards, pumas, gorillas at zoos and farmed mink and ferrets. The presence of the virus in animal species and an understanding of whether these are natural or recent human to animal transmissions is important. It’s possible that such transmission could passage the virus or subject the virus to a different immunological pressure thereby helping with the development of viral variants in addition to being a host for future reservoirs of the virus. In Kenya SARS-CoV-2 was first detected on March 12th 2020 from imported human cases of persons who had travelled from the United States. This was followed by detection of imported cases majorly from China, Sweden and United Kingdom. Later infections were confirmed in Nairobi and Mombasa suggesting further cases of disease importations through the major ports of entry. However, no comparable data on animal exposure have hitherto been generated in Kenya. To address this key concern, we focused on three objectives; 1) development of a robust antibody ELISA based on crude SARS-CoV-2 lysate. 2) SARS-CoV-2 serology of domestic animals in Kenya. 3) Corroboration of the crude lysate based seroprevalence data and a commercial ELISA kit based on the Spike receptor binding domain (RBD) antigen. Our sample set included camel sera (both pre- & post outbreak sera), as well as sera from cats and dogs collected at the peak of the pandemic. Our results using the ELISA based on crude SARS-CoV-2 lysate indicated SARS-CoV-2 antibodies in camels (71%, N=145), cats 11% (N=16) and dogs (81%, N=36) with varying titer levels. These findings were comparable to those obtained using the commercial ELISA kit based on the spike RBD antigens. In summary, the data warrants two key conclusions: (i) we have demonstrated that the crude lysate ELISA allows for SARS-CoV-2 antibody detection, and given its potential to offer robust detection could be applied for initial mass screening (ii) although the current study cannot disentangle the relative contributions of antigenic cross-reactivity, pre-pandemic exposure to SARS-CoV-2 or human-animal transmission, it nonetheless demonstrates for the first time the prevalence of SARS-CoV-2 like antibodies in domestic and wild animals in Kenya. Our findings set the scene for further research into the prevalence of SARS-CoV-2 in domestic and wild animals to understand their potential epidemiological implications.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.

Chromium (Cr) metal has garnered significant attention in alloy systems owing to its exceptional properties, such as high melting point, low density, and superior oxidation and corrosion resistance. However, its processing capabilities are hindered by the high Ductile-Brittle Transition Temperature (DBTT). Recently, powder bed fusion-laser beam for metals (PBF-LB/M) has emerged as a promising technique, offering the fabrication of net shapes and precise control over crystallographic texture. Nevertheless, research investigating the mechanism underlying crystallographic texture development in pure Cr via PBF-LB/M still needs to be conducted. This study explores the impact of scan speed on relative density and crystallographic texture. At the optimal scan speed, an increase in grain size attributed to epitaxial growth was observed, resulting in the formation of cubic texture. Consequently, a reduction in High Angle Grain Boundaries (HAGB) was achieved, suppressing defects such as cracks and enhancing relative density up to 98.1%. Furthermore, with increasing densification, Vickers hardness also exhibited a corresponding increase. These findings underscore the efficacy of PBF-LB/M for processing metals with high DBTT properties.

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.

K-band radar waves have high penetration and low attenuation coefficients. However, the wavelength of this radar wave is relatively short; thus, designing and preparing both broadband and wide-angle radar wave absorbers in this band presents considerable challenges. In this study, a resin-based K-band radar wave absorber with a biomimetic lotus leaf structure was designed and formed by UV curing. Here, microscale lotus leaf papillae and antireflection structures were prepared using a DLP 3D printer, and the contact angle between the material and water droplets was increased from 56° to 130°. In addition, the influence of the geometric parameters of the lotus leaf antireflection structure on the electromagnetic absorption performance and mechanical strength was investigated. After simulation optimization, the maximum electromagnetic loss of the lotus leaf structure 3D printed sample was −32.3 dB, and the electromagnetic loss was below −10 dB in the 20.8–26.5 GHz frequency range. When the radar incidence angle was 60°, the maximum electromagnetic loss was still less than −10 dB. The designed lotus leaf structure has a higher mechanical energy absorption per unit volume (337.22 KJ/m3) and per unit mass (0.55 KJ/Kg) than commonly used honeycomb lightweight structures during the elastic deformation stage, and we expect that the designed structure can be used as an effective lightweight material for K-band radar stealth.

The Fuzzy Transportation Problem (FTP) represents a significant extension of the Classical Transportation Problem (TP) by introducing uncertainly and imprecision into the parameters involved. Various algorithms have been proposed to solve the FTP, including fuzzy linear programming, metaheuristic algorithms and fuzzy mathematical programming techniques combined with Artificial Neural Networks. This paper presents the application of Trigonometric Acceleration Coefficients-PSO (TrigAc-PSO), a variation of the Classical Particle Swarm optimization algorithm, which is an innovative algorithm originally developed for solving the TP. TrigAC-PSO, has demonstrated remarkable success in optimizing various problem domains in crisp environments.

Cybersecurity is a crucial concern for local governments, as they serve as the primary interface between public and government services, managing sensitive data and critical infrastructure. While technical safeguards are integral to cybersecurity, the role of well-structured policy is equally important, as it provides structured guidance to translate technical requirements into actionable protocols. This study reviews local governments’ cybersecurity policies to provide a comprehensive assessment of how these policies align with NIST CSF, which is a widely adopted and commonly used cybersecurity assessment framework. The review offers local governments a mirror to reflect on their cybersecurity stance, identifying potential vulnerabilities and areas needing urgent attention. The study further extends to developing a cybersecurity policy framework, which local governments can use as a strategic tool. It provides valuable information on crucial cybersecurity elements that local governments must incorporate into their policies to protect confidential data and critical infrastructure.

Aural rehabilitation with hearing aids can decrease the attentional requirements of cognitive resources by amplifying the deteriorated-frequency sound in hearing loss patients and improve the auditory discrimination ability like speech-in-noise perception. As aural rehabilitation with an intelligible-hearing sound also can be hopeful, the aim of this study was to evaluate the effectiveness of the aural rehabilitation with intelligible-hearing sound for hearing loss patients. Adult native Japanese speakers (17 males and 23 females, 68.43±9.23 years) showed over 30 dB at 125, 250, 500, 1000, 2000, 3000, 4000, 8000, 10000, and 12000Hz on any side, were recruited and underwent Mini-Mental State Examination Japanese. we conducted self-evaluation questionnaire for hearing problems of voice, gap detection test, fast speech test, and speech-in-noise test, pure tone audiogram, speech perception test using Japanese 67-S, cortical auditory evoked fields, and magnetic mismatch negativity before and after the non-intelligible-hearing (N=20) and intelligible-hearing (N=20) sound therapy with listening to music for one hour a day for 35 days. Better hearing ear was defined using a four-frequency pure-tone average at the thresholds of 500, 1000, 2000 and 4000 Hz. After the sound therapy, speech-in-noise test with signal to noise ratio +10 in better hearing ear showed significant improvement (p&lt;0.05), and N1m-P2m amplitudes showed the significant increase in Lt superior temporal gyrus at the stimulus from better hearing ear (p&lt;0.05). The significant enhancement of the magnetic mismatch negativity amplitude at Lt superior temporal gyrus was exhibited after the sound therapy (p&lt;0.01). Intelligible-hearing sound therapy can improve the ability of speech-in-noise perception in better hearing ear and the enhancement of central cortex response, which reflect the ability of working memory, was proved by cortical auditory evoked fields and magnetic mismatch negativity. Intelligible-hearing sound therapy can be a valuable aural rehabilitation method for sensory neural hearing loss as same as hearing aids.

Arf-like protein 2 (ARL2) is a ubiquitously expressed small GTPase with multiple functions. In cell culture, ARL2 participates with tubulin cofactor D (TBCD) in the neogenesis of tubulin αβ-heterodimers, the building blocks of microtubules. To evaluate this function in retina, we conditionally deleted ARL2 in mouse retina at two distinct stages, either during embryonic development (retArl2-/-) or after ciliogenesis specifically in rods (rodArl2-/-). retArl2-/- retina sections displayed distorted nuclear layers and a disrupted microtubule cytoskeleton (MTC) as early as postnatal day 6 (P6). Rod and cone outer segments (OS) did not form. By contrast, rod ARL2 knockouts were stable at postnatal day 35 and revealed normal ERG responses. Cytoplasmic dynein is reduced in retArl2-/- inner segments (IS), suggesting that dynein may be unstable in the absence of a normal MTC. We investigated microtubular stability in the absence of either ARL2 (retARL2-/-) or DYNC1H1 (retDync1h1-/-), the dynein heavy chain, and found that both the retArl2-/- and retDync1h1-/- retinas exhibited reduced microtubules and nuclear layer distortion. The results suggest that ARL2 and dynein depend on each other to generate a functional MTC during early photoreceptor development.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

The origin of a product, consumer familiarity, and purchasing identity are factors that affect perception of cheese consumption. The present study aims at identifying consumers’ conceptualizations and attitudes towards local Greek cheeses of the North-Aegean Sea islands, such as Ladotyri, Graviera, Kasseri, Kaskavali, Melichloro, and Kalathaki, some of which have a Protected Designation of Origin (PDO) status, as opposed to cheeses of non-Greek origin, such as Cheddar, Regatto, and Gouda. Sensory and emotional attributes of local, local PDO, and imported cheeses, and drivers associated with consumers’ choice and acceptance above and beyond their sensory attributes were studied, using three methods: a) Flash Profile to gain insight into the sensory positioning of products and description of samples, b) qualitative analysis of focus groups to pinpoint consumer knowledge, preference, and consumption criteria, and c) a new methodology for natural language processing and sentiment analysis of social media posts to determine consumer conceptualizations. Social media posts have proven to be a valuable source of linguistic and cultural data for cheeses. Local cheeses, including PDO products, were found to be linked to village life and family gatherings, home, tradition, and childhood memories, with saltiness and hardness being their main sensory attributes. Imported cheeses were linked to fast food, pizza, and snacking, with elasticity and gumminess as prominent sensory qualities. The main criterion of purchase was intended usage and versatility, taste and texture, price, and familiarity. The findings provide key sensory attributes, information about consumer purchasing criteria, and relevant vocabulary for the promotion of cheeses as agri-food and gastronomic identity key products.

In the recent past about 40 botulinum neurotoxin (BoNT) subtypes belonging to serotypes A, B, E, and F pathogenic to humans were identified among hundreds of independent isolates. BoNTs are the etiological factors of botulism and represent potential bioweapons, but are also recognized pharmaceuticals for efficient counteraction of hyperactive nerve terminals in a variety of human diseases. The detailed biochemical characterization of subtypes as the basis for development of suitable countermeasures and possible novel therapeutic applications is lagging behind the increase in new subtypes. Here we report the primary structure of a ninth subtype of BoNT/F. Its amino acid sequence diverges by at least 8.4% at the holotoxin and 13.4% on the enzymatic domain level from all other known BoNT/F subtypes. We found that BoNT/F9 shares the scissile Q⁵⁸/K⁵⁹ bond in its substrate vesicle associated membrane protein 2 with the prototype BoNT/F1. Comparative biochemical analyses of four BoNT/F enzymatic domains showed that the catalytic efficiencies decrease in the order F1 > F7 > F9 > F6 and vary by up to factor eight. K_M values increase in the order F1 > F9 > F6 ≈ F7, whereas k_cat decreases in the order F7 > F1 > F9 > F6. Comparative substrate scanning mutagenesis studies revealed a unique pattern of crucial substrate residues for each subtype. Based upon structural coordinates of F1 bound to an inhibitor polypeptide the mutational analyses suggest different substrate interactions in the substrate binding channel of each subtype.

Flexible wearable pressure sensors offer numerous benefits, including superior sensing capabilities, a lightweight and compact design, and exceptional conformal properties, making them highly sought after in various applications including medical monitoring, human-computer interaction, and electronic skin. Because of their excellent characteristics, such as simple fabrication, low power consumption, and short response time, capacitive pressure sensors have received widespread attention. As a flexible polymer material, polydimethylsiloxane (PDMS) is widely used in the preparation of dielectric layers for capacitive pressure sensors. The Young's modulus of the flexible polymer can be effectively decreased through the synergistic application of sacrificial template and laser ablation techniques, thereby improving the functionality of capacitive pressure sensors. In this study, a novel sensor was developed through a series of processes including sacrificial template method using NaCl microparticles, CO₂ laser ablation, and sandwiching a porous PDMS dielectric layer between two flexible electrodes to create a capacitive pressure sensor. The sensor demonstrates a sensitivity of 0.694 kPa-1 within the pressure range of 0-1 kPa, and can effectively detect pressures ranging from 3 Pa to 200 kPa. The sensor demonstrates stability for up to 500 cycles, with a rapid response time of 96ms and a recovery time of 118ms, coupled with a low hysteresis of 6.8%. Furthermore, our testing indicates that the sensor possesses limitless potential for use in detecting human physiological activities and signaling emergencies.

We hypothesis that large earthquakes generate Horndeski-like Gravitational Wave (GW). We find that such a Horndeski-like GW propagates with the speed of sound. The sound waves generated by an earthquake make a local and temporal change to the Earth’s diagravitational medium; therefore, they modify the GW speed in a standard, Alternative-Theory-of-Gravity (ATG) sense. The quantum of the Horndeski-like GW is a massless scalar quasiparticle and cannot exist outside of the propagation region of the P-field. The Horndeski-like GW may be detectable by future GW detectors with a sensitivity of 10−15 Hz^−1/2 in the region of 0.1–1 Hz.

AbstractIntroduction: Consistent utilization of institutional delivery service reduces maternal morbidity and mortality. However, service utilization could in turn influenced by the women’s satisfaction with the service provided by the health care providers. In addition, their satisfactions with the institutional delivery service remains understudied. Assessment of the maternal satisfaction with maternal health service is a major input to improve maternal health services. Objective: To assess the maternal satisfaction with maternal health service and its predictors among the women who gave birth in last 12 months in Darara district, Southern Ethiopia.Methods: A community-based cross-sectional study was done using a mixed method among the sample of 520 women in Darara district, South Ethiopia from June 1-30, 2023. A systematic and purposive sampling procedure was utilized to choice the study subjects. A structured, validated and pretested interview-administrated questionnaire and in-depth interview were utilized to collect the data. The data were entered into Epi data version 3.1 and analyzed using SPSS version 25. The chi-square (X²) test was utilized to determine the overall association between independent and dependent variables. Both bi-variable and multivariable binary logistic regression analyses were conducted. Important assumptions of the binary logistic regression were checked to be satisfied. The coding and analysis of the qualitative data were done using thematic content analysis technique by Atlas-Ti software and presented in narratives. Results: The total maternal satisfaction with maternal health service was 55.2% (95% CI = 50.8-59.4). The identified predictors of maternal satisfaction were distance from household to health post (AOR = 3.59; 95% CI= 1.71 - 7.55), absence of preparation of HEWs during procedure (AOR= 2.87; 95% CI = 1.74 - 4.74), acceptability of the HES by HHs (AOR= 2.18; 95% CI = 1.14 - 4.18), having a reliable communication method with HEWs (AOR = 3.47; 95% CI = 1.77 - 6.79) and received training on the model family (AOR= 2.48, 95% CI= 1.86 - 2.57). These quantitative results were supported by the individual, organizational, socio-demographic and cultural qualitative findings. Conclusions: This study indicated that 55.2% of women were satisfied with maternal service.Distance from household to health post, absence of preparation of HEWs during procedure, acceptability of the Health Extension Service (HES) by household, having a reliable communication method with HEWs and received training on the model family were significant predictors of maternal satisfaction. The interventions to increase maternal satisfaction with HES need to focus on household-based acceptability of them and their reliable communication method in planning and implementing the services. Similarly, expansion of training of model family in the community would increase maternal satisfaction levels.

Background: Visceral leishmaniasis affects approximately 12 million people worldwide. Current existing drugs cause several side effects and resistance, the identification of new therapeutic targets for the development of new drugs is necessary. The vesicular trafficking in the parasite flagellar pocket is essential for parasite survival and proliferation, but little is known about the proteins involved in the endocytic/secretory pathways. In this work, we are describing the characterization of a transporter cargo protein SFT-2/Got-1 like in Leishmania infantum. Material and Methods: Using bioinformatics tools, the putative Got-1 protein A4HSK3 was characterized structurally and phylogenetically. Molecular biology was used to clone and express the protein and confocal fluorescence to determine its subcellular localization. Results: The Got-1 like protein presents four alpha helix TM conserved domains (aa38-aa147) characteristics of the Got-1/SFT-2 family proteins and an important Pen-2 conserved motif LGDYXXF located in the extracellular loop. Confocal microscopy suggests that Got-1/SFT-2 like is localized in the flagellar pocket, and is partially co-localized with the L. infantum presenilin-like protein. Phylogenetically, the Leishmania sp Got-1 like is contained in a subgroup of proteins clearly detached from the other Trypanosomatidae, such as T. cruzi and T. brucei. Conclusions: Our data show the presence of an important transported proteins, and its colocalization with the presenilin aspartyl protease in the flagellar pocket of the L. infantum open new perspectives to identify novel targets, which can be an alternative therapeutic strategy against leishmaniasis.

Observe the synergistic effect and dose-effect relationship of Trimethoprim (TMP) on bactericidal activity with Flos Lonicerae in vitro. Microamount chessboard dilution method was conducted to determine the minimal inhibitory concentration (MIC) of Trimethoprim, Flos Lonicerae, as well as the combination of Trimethoprim and Flos Lonicerae separately against Staphylococcus aureus, Escherichia coli in vitro and Salmonella. The pour plate count method was used to determine the combined bactericidal activity of Flos Lonicerae combined with Different concentrations TMP. The results showed that the MIC values of the combination of Flos Lonicerae with TMP was much less than the MIC values of the independent use of Flos Lonicerae or TMP, The FIC values of the combination of Flos Lonicerae with TMP were between 0.5 and 1, there was additive effect between them. The bactericidal rates were fitted with least square method, the 95% confidence intervals of the optimal blending quantity about the combination of Flos Lonicerae with TMP on the test organisms were 231μg·mL^-1-249μg·mL^-1, 237μg·mL^-1-259μg·mL^-1, and 235 -259μg·mL^-1

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

The efficacy and safety of organic UV-filters could benefit from their incorporation into lipid nanoparticles because of the ability of such carriers to reflect solar radiations, thus acting synergically as physical sunscreens. In this work, bemotrizinol (BMTZ), a broad-spectrum UV-filter, was loaded into nanostructured lipid carriers (NLC) whose lipid matrix contained different oils to assess the effects of the lipid core composition on the properties of the resulting NLC. Subsequently, the effects of incorporating different concentrations of optimized BMTZ-loaded NLC on the technological properties of O/W emulsions (pH, viscosity, spreadability, occlusion factor, in vitro BMTZ release and skin permeation, in vitro sun protection factor) were assessed. Optimized BMTZ-loaded NLC showed mean size=190.6±9.8 nm, PDI=0.153±0.013, ζ-potential=-10.6±1.7 mV, loading capacity=8% w/w. The incorporation of increasing concentrations of optimized BMTZ-loaded into emulsions provided slight increase of spreadability, lower viscosity and no change of pH, occlusion factor and BMTZ release compared to the control. No BMTZ skin permeation was observed from all formulations. About 20% increase of sun protection factor values was obtained for vehicles containing BMTZ-loaded NLC. Therefore, BMTZ-loaded NLC incorporation into emulsions could be a promising strategy to develop safer and more effective sunscreen formulations.

NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assay has some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo expansion of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examining cancer and immune cells in whole tumor samples and avoiding false negatives in histological assays.

The paper provides and comments on the results of studies of the effect of sandstone-based abrasives and quartz sand alone on the wear of martensitic surfaces of wear-resistant steels. The wear process was examined on a ring-on-ring test rig seeking to determine the mass decrement parameter which characterised wear. The tests were conducted for three sandstone varieties: Carboniferous, Permian, and Cretaceous, and they made it possible to determine that the most intense process of deterioration of wear-resistant steels took place in the presence of quartz sand grain, while less intense wear was observed in the case of sandstone-based abrasives. The mass decrement values established in the presence of the sandstones in question did not differ significantly between individual sandstone varieties. Based on a surface damage analysis, the basic damage mechanism was found to be micro-scratching, however, with regard to the sandstones examined, it was also determined that individual grains could be pressed into surface irregularities, as well as that films of soft hematite cement developed in the Permian sandstone and that inclusions of carbonaceous matter were formed in the Carboniferous sandstone. With reference to the wear process observations, a wear model was described for the surface of the steels examined in the presence of sandstone-based abrasives.

Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prion-like domains are critical for virulence and the development of therapeutic targets; however, the prion-like domains in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in the SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike protein, since SARS-CoV-2 was the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of the spike protein is particularly interesting, since although the SARS-CoV-2 and SARS-CoV S proteins share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. Finally, we identified prion-like domains in the α1 helix of the ACE2 receptor that interact with the viral receptor-binding domain of SARS-CoV-2. Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interact with RBD have important functional roles in viral adhesion and entry.

Utilization of wasted heat instead of fuel combustion is effective to reduce primary energy consumption for mitigating global warming problem. Because wasted heat sources are not necessarily located close to areas of heat demand, one of the difficulties is that wasted heat has to be transferred from heat source side to heat demand side, which may require heat transportation over long distance. From this point we proposed and have examined new idea of heat transportation using ammonia-water as the working fluid which system is named Solution Transportation Absorption chiller, in short STA. Our previous studies of STA were mainly the experimental investigation with STA facility which cooling power was 25RT (90kW). As a result, the COP of STA was found almost same value 0.65 with the conventional absorption chiller without depending on the transportation distances. The simulation using AspenHYSYS also examined with same experimental condition. The experimental data showed good agreement with the simulation calculation. In this study, we examined the large-scale cooling power STA on simulation. The examination cooling powers were from 90 kW(25RT) to 3517 kW(1000RT). All cooling power achieved around COP 0.64 including pump power consumptions. In addition, we performed the dynamic simulation. As the results, there was no effect of pipeline size on the cooling capacities and mass flow rates. Furthermore, the stability time of the cooling capacities and mass flow rates were almost same regardless of the pipeline size and cooling capacity. In other words, STA may be achieved the same COP even though having various complex conditions compared with the conventional absorption chiller.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

Questionnaires for self-report of food-elicited emotions are an established practice in consumer studies. However, most tools are originally developed in English and translated into other languages, which limits their use. The aim of this study was to develop the first Greek emotion lexicon and measurement tool for consumers, using standard methodology and extending it. The lexicon was compiled using linguistic sources and extended using the World Wide Web and a popular social media platform for the collection of authentic language and usage data. Terms were also collected from consumers using questionnaires and a variety of stimuli. Terms collected from consumers only comprise: healthy, distrustful, curious, childish, impressed, tolerant, impatient It was validated by application in various case studies, providing discrimination across and within food categories, and by comparison to the Greek translation of a standard tool in English, the EsSense Profile. The comparison was conducted by measuring emotions elicited by six food categories and demonstrated that it is preferable to use emotion measurement tools developed in the linguistic and cultural context of intended use, as they convey consumers’ emotions naturally and more accurately. This tool can be used as a Check- or Rate- All-That-Apply questionnaire to measure consumer responses to food categories and products. The methodology and validation presented can be applied for the compilation of emotion lexicons in languages less studied than English.

Aβ peptides are known to bind neural plasma membranes in a process leading to the deposit of Aβ-enriched plaques. These extracellular structures are characteristic of Alzheimer’s disease, the major cause of late-age dementia. The mechanisms of Aβ plaque formation and deposition are far from being understood. A vast amount of literature describes the efforts to analyze those mechanisms, using a variety of tools. The present review focuses on biophysical studies, mostly carried out with model membranes, or with computational tools. The review starts by describing basic physical aspects of lipid phases, and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The methodological section is followed by the core of the review, a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort in understanding Aβ-bilayer binding. Concepts such as Aβ peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aβ-membrane interaction are separately identified and discussed.

The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

Walls-like structured monoclinic WO3 thin films were obtained by spray deposition method for further integration in gas sensors. For sensing applications, it is very important to achieve a high surface-to-volume ratio surface together with a proper thin films structure. The present communication reports on the effect of the sprayed solution volume variation (as a thickness variation element) on the detailed Raman spectroscopy for WO3 thin films with different thicknesses grown from precursor solutions with two different concentrations. Detailed analysis of the two series of samples shows that the growing thickness strongly affects the films morphology while their crystalline structure is only slightly affected. The Raman analysis contribute to refining the structural features clarifications. It was observed that, for both concentrations, the increase in thickness seems to slightly affect the stoichiometry of material and, in association with surface morphology variations, provide new possibilities for fine tuning of films properties towards enhanced as sensing applications. Further studies are ongoing.

In recent years, the focus of disease resistance and susceptibility studies in cattle have been on determining patterns in the innate immune response of key proteins, such as Toll-like receptors (TLR). In the bovine genome, there are 10 TLR family members and, of these, TLR2, TLR4 and TLR6 are specialized in recognition of bacterial ligands. Indigenous cattle breeds of Anatolia have been reported to show fewer signs of clinical bacterial infections, such as bovine tuberculosis and mastitis, and it is hypothesized that this might be due to a less stringent genetic selection during breeding. In contrast, Holstein-Friesian cattle have been under strong selection for milk production, which may have resulted in greater susceptibility to diseases. To test this hypothesis, we have compared the TLR2, TLR4 and TLR6 genes of Anatolian Black (AB), East Anatolian Red (EAR), South Anatolian Red (SAR), Turkish Grey (TG), and Holstein (HOL) cattle using Next Generation Sequencing. The SAR breed had the most variations overall, followed by EAR, AB, TG and HOL. TG had the most variations for TLR2 whereas SAR had the most variations in TLR4 and TLR6. We compared these variants with those associated with disease and susceptibility traits. We used exon variants to construct haplotypes, investigated shared haplotypes within breeds and determined candidate haplotypes for disease resistance phenotype in Anatolian cattle breeds.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

Amidst worsening climate change, drought stress imperils global agriculture, jeopardizing crop yields and food security, necessitating urgent exploration of sustainable methods like biopriming, harnessing beneficial microorganisms to bolster plant resilience. Recent research has revealed diverse biological compounds with versatile applications produced by Schizophyllum commune, rendering this fungus as a promising contender for biopriming applications. For the first time this study aimed to investigate,the potential of S. commune exo- (EPSH) and intra-PSH (IPSH), isolated from two strains: Italian (ITA) and Serbian (SRB) under submerged cultivation, in enhancing the resilience of Pisum sativum L. seeds through biopriming technique. Testing of seed quality of bioprimed, hydroprimed, and unprimed seeds was done using a germination test, under optimal and drought conditions. In optimal conditions, the IPSH SRB increased germination energy by 5.50% compared to the control, while the highest percentage of germination (94.70%) was shown after biopriming with PSH isolated from the ITA strain. Additionally, all assessed treatments resulted in a boost in seedling growth and biomass accumulation, where the ITA strain demonstrated greater effectiveness in optimal conditions, whereas the SRB strain showed superiority in drought conditions. The drought tolerance indices increased significantly in response to all examined treatments during the drought, with EPSH ITA (23.00%) and EPSH SRB (24.00%) demonstrating the greatest effects. Results demonstrate a significant positive influence of fungal PSH, indicating their potential as biopriming agents and offers insights into novel strategies for agricultural resilience in the face of changing environmental conditions.

A new heterocyclic compound, 2-(2,6-diisopropylphenyl)-1-methylimidazo[1,5-a]quinolin-2-ium tetrafluoroborate 1 was obtained from its precursor, N-(2,6-diisopropylphenyl)-N-(quinolin-2-ylmethyl)acetamide 2, by POCl3-mediated cyclization. For the first time – the tertiary acetamide 2, precursor of 1, was synthesized by using commercially available starting materials. The structure of 1 was unquestionably confirmed by 1H-, 13C-, 2D-NMR-, IR- spectroscopy and mass-spectrometry. Its optical properties were also studied.

In an era marked by swift technological progress, the pivotal role of Artificial Intelligence (AI) is increasingly evident across various sectors, including local governments. These governmental bodies are progressively leveraging AI technologies to enhance service delivery to their communities, ranging from simple task automation to more complicated engineering endeavours. While more and more local governments are adopting AI, it is imperative to understand the functions, implications, and consequences of AI. Despite the growing importance of this domain, a significant gap persists within the scholarly discourse. This study strives to bridge this void by exploring the applications of AI technologies within the context of local government service provision and using this inquiry to generate lessons and best practices for similar smart city initiatives. Through a comprehensive grey literature review, we analysed 262 real-world AI implementations across 170 local governments worldwide. The findings underscore several key points: (a) There has been a consistent upward trajectory in the adoption of AI by local governments over the last decade; (b) Local governments from China, the US, and the UK are at the forefront of AI adoption; (c) Among local government AI technologies, Natural Language Processing and Robotic Process Automation emerge as the most prevalent ones; (d) Local governments primarily deploy AI across 28 distinct services; (e) Information management, back-office work, and transportation and traffic management are leading domains in terms of AI adoption. This study enriches the extant body of knowledge by providing an overview of existing AI applications within the sphere of local governance. It offers insights for smart city policymakers and decision-makers considering the adoption, expansion, or refinement of AI technologies in urban service provision. Additionally, it underscores the importance of using these insights to guide the successful integration and optimisation of AI in future smart city projects, ensuring they meet the evolving needs of communities.

This study aimed to investigate the fatigue performance and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar lap joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Furthermore, the fatigue life of the 14 kV joints was one order of magnitude higher compared to the 12 kV joints. SEM observation of the fatigue fracture surface revealed the presence of typical "tire-mark" fatigue striations only in the 14 kV joint, indicating higher ductility and the ability to withstand extended plastic deformation. Notably, ultra-fine nanocrystalline Al2Cu phase, amorphous phase, and numerous dislocations hindered EBSD acquisition in the transition zone. Nevertheless, dense low-angle grain boundaries (LAGBs) and refined grains were examined at the bonding interface. This suggests that the high-velocity collision caused severe plastic deformation and led to the formation of substructures. The interfacial strength was attributed not only to the "wave-like" or "inverted hook-like" diffusion layer but also to the presence of refined grains along the interface and nanocrystalline Al2Cu in the transition zone. Furthermore, the hybrid nanocrystalline-amorphous microstructure strengthened the joint by regulating the balance between strength and ductility.

. Protein cysteine S-glycosylation is a relatively rare and less well characterized post-translational modification (PTM). Creating reliable model proteins that carry this modification is challenging. The lack of available model or natural S-glycosylated proteins significantly hampers the development of MS-based methodologies for detecting protein cysteine S-glycosylation in real-world proteomic studies. There is also limited MS-sequencing data describing easier to create synthetic S-glycopeptides. Here, we present the results of an in-depth manual analysis of automatically annotated CID/HCD spectra for model S-glucopeptides. The CID spectra show a long series of y/b-fragment ions with retained S-glucosylation, regardless of the dominant m/z signals corresponding to neutral loss of 1,2-anhydroglucose from the precursor ions. In addition, the spectra show signals manifesting glucosyl transfer from the cysteine position onto Lys, Arg side chains, and a peptide N-terminus. Other spectral evidence indicates that the N-glucosylated initial products of transfer are converted into N-furanosylated (i.e., glycated) structures due to Amadori rearrangement. We discuss the peculiar transfer of the glucose oxocarbenium ion (Glc+) to positively charged guanidinium residue (ArgH+) and propose a mechanism for the gas-phase Amadori rearrangement involving a hydride ion shift.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Resveratrol (RSV), a naturally occurring phytoalexin, is the most important stilbenoid synthesized by plants, as a defense mechanism, in response to microbial aggression, toxins or ultraviolet radiation. RSV came to the attention of researchers both as a potential chemopreventive agent and a possible explanation for the low incidence of cardiovascular disease (CVD) in French people with a high-fat diet. RSV is mainly administered as a food supplement, its properties being evaluated in vitro or in vivo, on various experimental models. RSV modulates signaling pathways that limit the spread of tumor cells, protects nerve cells from damage, is useful in the prevention of diabetes, and generally acts as an anti-aging natural compound. It was highlighted that RSV could ameliorate the consequences of an unhealthy lifestyle caused by an exaggerated caloric intake. This paper reviews the evidence supporting the beneficial effect of RSV for various pathological conditions, e.g., neoplastic diseases, neurodegeneration, metabolic syndrome, diabetes, obesity, CVDs, immune diseases, bacterial, viral, and fungal infections. The study also focused on the chromatographic analysis of trans-RSV (tRSV) in Romanian wine samples, providing a comprehensive overview of tRSV content across different types of wine.

Rosemary is one of the most important medicinal plants for natural therapy due to its multiple pharmacological properties, such as antioxidant, anti-inflammatory, neuroprotective, antiproliferative, antitumor, hepato- and nephroprotective, hypolipidemic, hypocholesterolemic, antihypertensive, anti-ischemic, hypoglycemic, radioprotective, antimicrobial, antiviral, antiallergic, wound healing. Our study reports for the first time, over a 12-month period, the identification and quantification of polyphenols and the investigation of the antioxidant and acetylcholinesterase (AChE) inhibitory activity of the Rosmarinus officinalis L. species harvested at flowering from the flora of southwestern Romania (Oltenia Region). Identification and quantification of polyphenolic acids was made by ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS). Total phenolic content was determined using the spectrophotometric method. In situ antioxidant and anticholinesterase activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and AChE inhibitory assay, respectively, on high-performance thin-layer chromatography (HPTLC) plates. DPPH radical scavenging activity was also assessed spectrophotometrically. The results revealed significant correlations between specific polyphenolic compounds and the measured biological activities, understanding the role of seasonal variations and providing insights into the optimal harvesting times and medicinal benefits of rosemary. Our research brings new information on the phytochemical profile of R. officinalis, as a natural source of polyphenols with antioxidant and AChE inhibitory properties.

In this paper, we consider the synchronization of chaotic oscillators interconnected via a second order dynamic coupling. The design of the proposed coupling is inspired in the ancient synchronization experiment of synchronized pendulum clocks, as described by the Dutch scientist Christiaan Huygens more than three centuries ago. It is demonstrated that the coupled chaotic systems may exhibit not only complete synchronization, but also mixed synchronization—some states synchronize in anti-phase whereas other states synchronize in-phase. In fact, a transition from complete synchronization to mixed synchronization or viceversa can be induced by just changing a single parameter in the coupling. Additionally, the stability of the synchronous solution is investigated by using the Master Stability Function approach and the largest transverse Lyapunov exponent. The Lorenz system is considered as particular application example. Finally, the performance of the proposed synchronization scheme is illustrated with computer simulations and validated by means of experiments using electronic circuits.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

This study explored the effects of cryogenic treatment on the microstructure, hardness, and wear-resistance of diamond-like carbon (DLC) by cryogenically treating NAK 80 mold steel coated with DLC. Raman spectroscopy analyzed the structure of the DLC film. Nanoindenter analyzed the hardness and Young’s modulus of the film, and their relationship determined the wear resistance. Wear test assessed the wear rate and friction coefficient of the DLC film. The results showed that cryogenic treatment increased the rate of carbide precipitation and refined the grain structure. Raman spectroscopy indicated that the Raman intensity rate (I_D/I_G) of treated DLC films was smaller than those without cryogenic treatment. When the sp3 bond increased, the hardness and wear-resistance of the DLC film also increased.

2017 was an excellent year in terms of new drugs (chemical entities and biologics) approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, synthetic strategy used for their production, source, biological target, and mode of action.

In the Vietnamese Mekong delta, soil quality and crop yield are steadily declining under rice monocultures with three crops per year. The objective of this study was to evaluate the medium-term effects of rotating rice with upland crops and adding organic amendments on rice yield and relate it to soil quality. A field trial with split-plot design including two factors and three replicates was carried out from 2017 to 2020, over the course of nine consecutive cropping seasons. Crop rotations and organic amendments were applied as main-plot and subplot factors, respectively. The rotations were: 1) rice–rice–rice (R–R–R), 2) soybean–rice–rice (So–R–R), and 3) sesame–rice–rice (Se–R–R), while organic amendment treatments included: i) no amendment (NO-AM); ii) compost of rice straw and cow manure (RS+CM), and iii) sugarcane compost (SGC); the composts were applied at a rate of 2.0 t ha-1. The rotation cycle started with the so-called spring–summer (SS), followed by summer–autumn (SA) and ended with the winter–spring (WS) season. Rice yield significantly (P &lt; 0.05) increased by organic amendments after nine growing seasons (2019–2020 WS), with an increment of 5.1% for RS+CM (7.07 ton/ha) and 6.1% for SGC (7.14 ton/ha). Contrary to our expectation, rotations with upland crops did not significantly increase rice yield. Rice yield significantly and positively correlated with an integrated soil quality index SQI (r = 0.86) for the topsoil (0–15 cm), but not for the subsoil (15–30 cm). The increased availability of soil nutrients (Si and marginally also P) and improved soil physical properties probably induced by organic amendments, along with other soil properties under study, cumulatively attributed to enhanced rice yield. Use of a SQI involving several soil quality indicators enables to overall quantify the importance of soil fertility for rice yield versus other factors and it provides an effective means of quantifying the integrated effect of improved management. Moreover, integrating a wide range of soil quality indicators in a SQI ensures its applicability across diverse settings, including different crop rotations and various soil types.

The reaction of 2-((diphenylmethylene)amino)acetonitrile with (E)-1-phenyl-3-(thiophen-2-yl)prop-2-en-1-one was performed by using 33% NaOH in CH3CN for 30 min at 0°C. The main product - rel-(2R,3S)-2-((diphenylmethylene)amino)-5-oxo-5-phenyl-3-(thiophen-2-yl)pentanenitrile was isolated and characterized by IR, 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS).

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

The mechanical properties of the materials stored inside agricultural silos influence the loads generated inside them. The different silo calculation methodologies allow predicting these loads under static and dynamic conditions if the mechanical properties of the stored materials are known. It has been known for many years that these properties are highly dependent on the moisture content of the material. However, to date there are not many studies focused on its determination. The goal of this research is the determination of the angle of internal friction, apparent cohesion, dilatancy angle and apparent specific weight of maize subjected to different moisture contents. Direct shear and oedometer assay devices were used for this purpose. In addition, the maize samples used were moistened using a climatic chamber. Moisture contents applied to maize sample ranged from 9.3% to 17.4%. The results obtained for the angle of internal friction and apparent cohesion, as well as those obtained for the apparent specific weight, were similar to those reported in the literature. However, the values obtained for the dilatancy angle of maize as a function of moisture content could not be compared because nothing has been published so far. The values obtained for this parameter overlap with those published for this material under ambient conditions. In addition, no direct relationship between the values obtained for this parameter and the moisture content of the sample could be found. Finally, the apparent specific weight increased with increasing moisture content of the samples, which differed from that published in the literature. The values provided here can be used for the optimization of storage and handling structures for granular agricultural materials using numerical methods.

Levels of trace element pollution in surface soil can be estimated using soil analyses and leaching tests. These methods may reveal different results due to the effect of soil properties, such as grain size and mineral composition, on elemental availability. Therefore, this study advocates an alternative method for monitoring and assessment of trace element pollution in surface soil using terricolous fruticose lichens. Lichens growing at abandoned mine sites and unpolluted areas in southwest Japan and their substrata were analyzed using inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry to clarify the relationships between Cu, Zn, As, and Pb concentrations in lichens and soils, including their absorption properties. Concentrations of these elements in the lichens were positively correlated with those in the soils regardless of lichen species, location, habitat, or conditions of soils. The analyzed lichens had neither competitive nor antagonistic properties in their elemental absorption, which made them good biomonitors of trace element pollution in surface soil. The distribution maps of average Cu, Zn, As, and Pb concentrations at each sampling region detected almost all of the Cu, Zn, and As pollution of the soils. Therefore, lichens could be used in practical applications to monitor Cu, Zn, and As pollution in surface soils.

A 7.4 m long sediment core has been retrieved from the central part of Lake Vrana on the Island of Cres to reconstruct the paleoenvironmental conditions. Lake Vrana is the deepest freshwater lake in Croatia, located in the karst region of the eastern Adriatic coast. A dated sediment sequence in Lake Vrana of 4.4 m spans the past 16.4 kyr, and features a dynamic sediment deposition until the beginning of the Holocene, including strong sediment input and supply to the lake by runoff sediments of dolomitic origin from the catchment in the period 16.4-14.4 cal kyr BP. High organic carbon content, which originates from mixed terrestrial and aquatic origins in the periods 14.4-13.3 cal kyr BP and 12.7-11.7 cal kyr BP, indicates fluctuating lake levels in shallow water environments during the late glacial to Holocene transition. The Holocene sequence indicates the development of more stable conditions and continuous sediment deposition, characterized by increasing trend of siliciclastic sediments delivered into the lake during the early Holocene (11.7-10 cal kyr BP), and dominantly from 8 to 4.4 cal kyr BP, indicating enhanced input and erosion, which coincides with humid and pluvial period, recorded in the central Mediterranean region. It is followed by sediments with high organic carbon content between 4.4 to 1.6 cal kyr BP, which points to higher lake productivity. Calcite sedimentation prevail between 1.6 to 0.4 cal kyr BP, indicating stable deeper-lake conditions, while dominantly siliciclastic sediments in the period 0.4-0.1 cal kyr BP indicate erosion during Little Ice Age (LIA), with enhanced precipitation and sediment discharge from the catchment. The re-establishment of calcite sedimentation has been observed over the last 100 years.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

This article is devoted to the results of in-depth analysis of the system of binary-oppositional structures in DNA n-plet alphabets and their algebraic-matrix representations. These results show that the molecular complementary replication of DNA strands is accompanied by the presence of an algebraic version of the principle "like begets like" in matrix representations of DNA alphabets having internal structures. This algebraic version is based on binary-oppositional structures in the genetic molecular system, which can be represented by binary numbers and corresponding matrices of DNA alphabets. The received results allow thinking that the phenomenon "like begets like" (or a complementary replication in a wide sense) is systemic in the genetic organization and is connected with algebraic features of biological organization. Correspondingly, the biological principle "like begets like" can be additionally modeled by algebraic-matrix methods and approaches. Such algebra-matrix modeling of the genetic coding system gives new ways for studying and understanding the key role of the named principle in genetic and other inherited physiological complexes. On this way, the author discovered general rules of stochastic organization of information binary sequences of genomic DNAs of eukaryotes and prokaryotes. The presented rules are connected with information dichotomies of probabilities and corresponding fractal-like trees of probabilities, which fundamentally differ from constructional dichotomies in biological bodies. The received phenomenological data and rules lead to new biological ideas.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

: This study focuses on optimizing chlorophyll extraction techniques and strategically placing leaf disks to enhance chlorophyll concentration in sesame (Sesamum indicum L.) leaves. Thirty sesame genotypes, categorized into light green (LG), middle green (MG), and deep green (DG) pigment groups based on leaf coloration, were selected from a larger pool of field-grown accessions. The investigation involved determining optimal SPAD value index measurements, quantifying pigment concentrations, exploring extraction solvents, and selecting suitable leaf disk positions. Significant variations in chlorophyll content were observed across genotypes, greenness categories, and leaf disk positions. The categorization of genotypes into DG, MG, and LG groups revealed a correlation between leaf appearance and chlorophyll content. The study highlighted a consistent relationship between carotenoids and chlorophyll, indicating their role in adaptation to warm environments. Examination of leaf disk positions revealed a significant chlorophyll gradient along the leaf blade, emphasizing the need for standardized protocols. Chlorophyll extraction experiments identified DMSO and 96% ethanol, particularly the later incubated for 10 minutes at 85°C, as effective choices. This recommendation considers factors like cost-effectiveness, time efficiency, safety, and environmental regulations, ensuring consistent and simplified extraction processes. For higher chlorophyll extraction, focusing on leaf tips and the 75% position along the sesame leaf blade is suggested, consistently yielding higher chlorophyll content. Our findings therefore, underscores insightful knowledge on chlorophyll gradients and encouraging for standardized protocols, that enabling researchers to refine experimental designs for precise and comparable chlorophyll measurements. Recommended solvent choices ensure reliable outcomes in plant physiology, ecology, and environmental studies.

Minigastrin (MG) analogs for therapy of CCK2R-expressing malignancies are limited by low stability in vivo or excessive accumulation in non-target organs. By modifying the C-terminal receptor-binding sequence, metabolization could be prevented and tumor targeting significantly improved. In this work, N-terminal changes of the peptide length were evaluated. Based on the amino acid sequence of DOTA-MGS5 (DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1Nal-NH₂), two new MG analogs were synthesized, by either introduction of a penta-DGlu moiety or depletion of the four N-terminal amino acids and introduction of a non-charged hydrophilic linker. Two CCK2R-expressing cell lines were used to demonstrate receptor interaction. Stability of the ¹⁷⁷Lu-labeled peptide analogs was evaluated in human serum up to 24 h after incubation and in BALB/c mice up to 30 min after injection. The biodistribution profile and tumor targeting potential was evaluated in xenografted BALB/c nude mice. For both new MG analogs, the combination of strong receptor-specific cell interaction, high stability and enhanced tumor targeting could be demonstrated. Shortening of the peptide sequence lowered the absorption in the dose-limiting organs, whereas elongation increased uptake in renal tissue.

Background: Removable prostheses have seen a fundamental change recently because of advances in polymer materials, allowing improved durability and performance. Despite these advancements, notable differences still occur amongst various polymer materials and processing technologies, requiring a thorough grasp of their mechanical, physical, and therapeutic implications. Methods: Fours different processing techniques, all utilizing Polymethyl methacrylate (PMMA) as the main material, were used to construct complete dentures. The specimens underwent a mechanical test. Results: All the specimens broke under the influence of a certain force, rather than yielding through flow, as is characteristic for plastic materials. For each specimen, the maximum force (N) was recorded (figure 4), as well as the breaking energy, Conclusions: The best results were obtained in the case of the thermoplastic injection system and, surprisingly and contrary to those in the specialized literature, the worst results were recorded in the case of 3D printed samples.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis

New furan, thiophene and triazole oximes were synthesized through several-step reaction paths to investigate their potential for development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Acute OP poisoning is still a challenge in treating patients despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, are blocked by the OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to cholinergic crisis. Oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper we described the synthesis of 63 heterostilbene derivatives out of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents – sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in micromolar range, we identified several oximes as BChE or AChE selective inhibitors with a potential for drug development. Moreover, even oximes were poor reactivators of AChE, four heterocyclic derivatives reactivated the cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had comparable reactivation efficacy to the standard oxime HI-6. In silico analysis and molecular docking studies connected the kinetic data to the structural features of these oximes, and confirmed their productive interactions with the active site of the cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases like Alzheimer’s and Parkinson’s.

Brand trust holds significant importance in the Mongolian cashmere industry. This study examines the primary predictors of customer brand trust among Mongolian cashmere users. Our research includes a survey with 800 participants and 20 individual interviews conducted among both Mongolian cashmere users and non-users. We utilized an online platform to reach participants, employing convenience sampling. The study investigates the relationship between various factors and brand trust within the context of Mongolian cashmere brands. Through a combination of in-dividual interviews and statistical analysis, we test six hypotheses. The findings indicate that higher brand quality, a strong reputation, greater transparency, effective issue resolution, commitment to environmental and social responsibility, and pre-purchase research on such commitments positively impact brand trust. Key insights gleaned from the interviews emphasize the importance of quality, reputation, transparency, customer service, and environmental responsibility in shaping consumer trust. These results offer valuable implications for cashmere brands aiming to bolster consumer trust and foster loyalty.

Background: Atopic dermatitis is a chronic condition that significantly affects the daily life of those who suffer from it, requiring complex and personalized management with active participation of the patient in the management of their disease. Objective: to describe the design and development process of a mobile application, using the Design Thinking method, for the follow-up of patients with atopic dermatitis. Methods: User-centered design and prototype creation method, differentiating the phases of the empathize, define, idea, prototype, and test. A purposive snowball sampling was used to recruit patients with atopic dermatitis, family members, and health professionals. Three two-hour workshops were held, attended by 25 people. Results: the parameters to be monitored will include objective data (physical, behavioral, treatments, environmental, integration of daily routines) and subjective data (user experience). On the other hand, it will figure out behavior patterns, set up rewards, foster a feeling of community, and use notifications and a chatbot. Conclusion: The active integration of all stakeholders at each stage of the design and development of the digital solution has improved its relevance and acceptance, resulting in a tool that is expected to significantly improve the management of atopic dermatitis.

The growing expansion of the economy and population has resulted in an increased inclination towards the utilization of groundwater resources. Conducting a geophysical survey is a widely employed method for subsurface mapping and the detection of groundwater. A geophysical study was conducted in Nanshan township, Huarong County, located in the Hunan province of the South-Central region of China. The investigation involved the utilization of a 2D Electrical Resistivity Imaging technique employing forward and inverse pole-dipole electrode array. A total of six survey lines were established, each with an electrode distance from the nearest measuring point to exceeding 800 m. The maximum current electrode separation was utilized in this setup. The spacing between the electrical resistivity sounding points was established at regular intervals. The findings from the exploration indicate the existence of multiple faults within the surveyed region. The study additionally identified two regions of structural failure, which occurred due to the convergence of faults oriented in different directions. This convergence led to the fracturing of rocks, an increase in water content, and a decrease in resistivity. The findings from the exploration were utilized in the formulation of five verification target boreholes. The results of this study offer significant insights that can inform future investigations into groundwater exploration endeavors within the region.

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.