Whether there is any inclination between structures and functions of antimicrobial peptides (AMPs) is a mystery yet to be unraveled. AMPs have various structures associated with many different antimicrobial functions, including antibacterial, anticancer, antifungal, antiparasitic and antiviral activities. However, none has yet reported any antimicrobial functional tendency within a specific category of protein/peptide structures nor any structural tendency of a specific antimicrobial function with respect to AMPs. Here we examine the relationships between structures categorized by three structural classification methods (CATH, SCOP and TM) and seven antimicrobial functions with respect to AMPs using an enrichment analysis. The results show that antifungal activities of AMPs were tightly related to two-layer sandwich structure of CATH, knottin fold of SCOP, and the first structural cluster of TM. The associations with knottin and TM cluster 1 even sustained through the AMPs with a low sequence identity. Besides, another significant mutual enrichment was observed between the third cluster of TM and anti-gram-positive-bacterial/anti-gram-negative-bacterial activities. The findings of the structure-function inclination further our understanding of AMPs and could help us design or discover new therapeutic potential AMPs.

Antimicrobial peptides provide a powerful toolkit for combating multidrug resistance. Combatting eukaryotic pathogens is complicated by the fact, the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria, (symbionts of entomopathogenic nematode species), release a series of non-ribosomal templated antimicrobial peptides, some may be potential drug candidates. The ability of an entomopathogenic nematode /entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product, explaining that those gene complexes which are responsible for the biosynthesis of different non-ribosomal templated antimicrobial protective peptides (including those which are potently capable to inactivate the protist mammalian -pathogen Leishmania and the gallinaceous bird pathogen Histomonas) are co-regulated. Our approach is based on comparative antimicrobial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated antimicrobial peptides, that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourages us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing EPB strains producing and releasing single, harmless, non-ribosomal templated antimicrobial peptides with considerable drug, (probiotic) -candidate potential.

Antimicrobial Peptides (AMPs), as immune effectors synthesized by a variety of organisms, not only constitute a robust defense mechanism against a broad spectrum of pathogens in the host, but also show promising applications as effective antimicrobial agents. Notably, insects are significant reservoirs of natural AMPs. However, the complex array of variations in types, quantities, antimicrobial activities, production pathways of AMPs, and evolution of AMPs across insect species presents a significant challenge for immunity system understanding and AMP applications. This review covers insect AMP discoveries, classification, common properties, and mechanisms of action. Additionally, we summarize the types, quantities, and activities of im-mune-related AMPs in each model insect. We also conducted the first comprehensive investigation into the diversity, distribution, and evolution of 20 types of AMPs in model insects, employing phylogenetic analysis to describe their evolutionary relationships and shed light on conserved and distinctive AMP families. Furthermore, we summarize the regulatory pathways of AMP production through classical signaling pathways and additional pathways associated with Nitric Oxide, insulin-like signaling, and hormones. This review advances our understanding of AMP as guardians in insect immunity system and also unlocks a gateway to insect AMP resources, facilitating the use of AMPs to address food safety concerns.

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

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

Many types of banana (Musa spp.)—one of the most economically important horticultural crops—exist, and their ploidy (diploid, triploid, and tetraploid, usually) and genome types (containing A or/and B genome in most cases) differ. At present, observation and genome type detection are commonly used to identify banana germplasm resources. However, the former is tedious, while the latter cannot distinguish categories below genome types. It is therefore urgent that a simple and effective method for identifying banana germplasm resources is established. We sequenced and analyzed the ribosomal DNA internal transcribed spacer (ITS) sequences of 62 banana germplasm and found that the sequencing peaks, especially the 20 bp region near the 420 bp position (referred to as the “420 bp region”), exhibited relatively recognizable and repeatable polymorphism characteristics. Using the “420 bp region” as a marker, we were able to quickly distinguish bananas belonging to different genome type groups (comprising the AA, AB, AAA, ABB, AAB, ABBB, AAAB, and AAAA groups) or different subgroups in the same genome type group (for example, the Cavendish, Gros Michel, Red, Lakatan, and Ibota Bota subgroups in the AAA group; and the Pisang Raja, Plantain, Pome and Silk subgroups in the AAB group). Moreover, it appeared that Sanger sequencing of ITS could be used for identifying banana hybrid offspring. These results demonstrated that the banana ITS region contains rich genetic information that is useful for genotyping. In general, ITS sequencing simplifies the classification of banana germplasm resources and has potential application in several areas of Musa improvement.

The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will discuss about the biogenesis and function of small non-coding RNAs derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs), and their potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because we could not believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

Antimicrobial peptides (AMPs) have emerged as a promising class of bioactive molecules with the potential to combat infections associated with medical implants and biomaterials. This review article aims to provide a comprehensive analysis of the role of antimicrobial peptides in medical implants and biomaterials, along with their diverse clinical applications. The incorporation of AMPs into various medical implants and biomaterials has shown immense potential in mitigating biofilm formation and preventing implant-related infections. We review the latest advancements in biomedical sciences and discuss the AMPs that were immobilized successfully to enhance their efficacy and stability within the implant environment. We also highlight successful examples of AMP coatings for the treatment of surgical site infections (SSIs), Contact lenses, Dental Applications, AMP-Incorporated Bone Grafts, Urinary tract infections (UTIs), Medical Implants, etc. Additionally, we discuss the potential challenges and prospects of AMPs in medical implants, such as effectiveness, instability and implant-related complications. We also discuss strategies that can be employed to overcome the limitations of AMP-coated biomaterials for prolonged longevity in clinical settings.

The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

Abstract: Antimicrobial peptides (AMPs) are short peptides, usually made up of less than 100 amino acid residues. They are found in many living organisms and are an important factor in their innate immune systems. AMPs can be extracted from various living sources including bacteria, plants, animals and even humans. They are usually cationic peptides with an amphiphilic structure, which allows them to easily bind and interact with the cellular membranes of viruses, bacteria, fungi and other pathogens. They can act against both Gram-negative and Gram-positive pathogens and have various modes of action against them. Some attack the pathogens membrane, while others target their intracellular organelles as well as their nucleic acids, proteins and metabolic pathways. A crucial area of use of AMPs is in their ability to help with emerging antibiotic resistance: some AMPs are active against resistant strains and are susceptible to peptide engineering. This review considers AMPs from three key sources: plants, animals and humans, as well as their modes of action and some AMPs sequences.

The informational synthesis of neural structures, processes, parameters and characteristics that allow a unified description and modeling as neural machines of natural and artificial neural systems is presented. The general informational parameters as the global quantitative measure of the neural systems computing potential as absolute and relative neural power were proposed. Neural information organizing and processing follows the way in which nature manages neural information by developing functions, functionalities and circuits related to different internal or peripheral components and also to the whole system through a non-deterministic memorization, fragmentation and aggregation of afferent and efferent information, deep neural information processing representing multiple alternations of fragmentation and aggregation stages. The relevant neural characteristics were integrated into a neural machine type model that incorporates unitary also peripheral or interface components as the central ones. The proposed approach allows overcoming the technical constraints in artificial computational implementations of neural information processes and also provides a more relevant description of natural ones.

Global agriculture has been forced to increase food production to feed the growing human population, while confronting various environmental obstacles such as global warming, resistance to pathogens, and constraints on arable land caused by soil salinity, drought, rising sea level, saltwater intrusion, and urbanization. Regarding abiotic stresses, salinity is a worldwide problem for agricultural production. Many efforts, therefore, have been made to cope with the environmental challenges, however, the progress of salinization, which is mainly caused and accelerated by anthropogenic activities, is likely faster than our progress in finding ways to deal with this problem. In addition, drought represents a global threat to the production of major crops. In addition, pests and pathogens cause significant crop losses and diminish global food security. Among the various strategies that have been investigated and applied in plant science, antimicrobial peptides derived from plants have caught widespread attention from scientists since these peptides exhibit beneficial biological activities. In agricultural science, there have been reports on the roles of antimicrobial peptides with active properties against biotic and abiotic stresses. Non-specific plant lipid transfer proteins, thionins, systemins, defensins, cyclotides, and heveins-like antimicrobial peptides are common antimicrobial peptides that have been found to be involved in the defense system against fungi and insect pests. Based on their potential ability to protect crops from pests, bacteria, and pathogenic fungi, the use of antimicrobial peptide genes in creating transgenic plants has been largely conducted during the last decades, and these studies have obtained positive results against the growth of fungi and bacteria. This review will focus on the latest progress in studies of antimicrobial peptides related to biotic and abiotic stress tolerance in plants. We will also update the current progress in the development of antimicrobial peptide-based transgenic crops.

Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides are a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development. A subfamily of AMPs interact with metal ions to potentiate their antimicrobial effectiveness, as such they have been termed metalloAMPs. In this work, we review the scientific literature of metalloAMPs that enhance their antimicrobial efficacy when combined with the essential metal ion, zinc (II). Beyond the role played by Zn(II) as a cofactor in different systems, it is well-known that this metal ion plays an important role in innate immunity. Here, we classify the different types of synergistic interactions between AMPs and Zn(II) into three distinct classes. By better understanding how each class of metalloAMPs uses Zn(II) to potentiate their activity, researchers can begin to exploit these interactions in the development of new antimicrobial agents and accelerate their use as therapeutics.

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

Alzheimer's Disease (AD) represents the most frequent type of dementia in elderly people. There are two major forms of the disease: sporadic (SAD) - whose causes are not completely understood - and familial (FAD) - with clear autosomal dominant inheritance. The two main hallmarks of AD are extracellular deposits of amyloid-beta (Ab) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein (P-tau). An ever-growing body of research supports the infectious hypothesis of sporadic forms of AD. Indeed, it has been documented that some pathogens, such as herpesviruses and certain bacterial species, are commonly present in AD patients, prompting recent clinical research to focus on the characterization of Antimicrobial Peptides (AMPs) in this pathology. Literature also demonstrates that Ab can be considered itself as an AMP thus representing a type of innate immune defense peptide that protect the host against a variety of pathogens. Beyond Ab, other proteins with antimicrobial activity, such as lactoferrin, defensins, cystatins, thymosin β4, LL37, histatin 1 and statherin have been shown to be involved in AD. Here we have summarized and discussed these findings and explored the diagnostic and therapeutic potential of AMPs in AD.

In our previous work, we demonstrated the potential of the amphiphilic cyclic peptide [W4R4] as a promising antimicrobial agent. The extensive data accumulated on the antimicrobial activity of this peptide and its homologs presented an opportunity to unravel the molecular mechanisms governing their action and establish crucial structure-activity relationships (SAR). To achieve this, we employed a comprehensive approach involving peptide synthesis, in vitro biological testing, and molecular modeling to systematically analyze the SAR of a series of cyclic peptides derived from the [W4R4] scaffold. Minimal modifications were introduced to the original peptide by incorporating either one aromatic hydrophobic residue (W) or one polar positively charged residue (R) while maintaining the sequential W/R arrangement. Additionally, we introduced an "intermediate" substitution by incorporating 2,5-diketopiperazine (DKP), possessing both aromatic and polar properties, into the macrocycle [W4R4] between the W and R residues. Notably, this study marked the first synthesis and evaluation of the [W4R4(DKP)] peptide. Structural, dynamic, hydrophobic, and membrane-binding properties of four cyclic peptides ([W4R4], [W5R4], [W4R5], [W4R4(DKP)]) were explored using molecular dynamics simulations within a DOPC/DOPG lipid bilayer that mimics the bacterial membrane. The results obtained revealed distinct SAR profiles for all peptides, enabling the establishment of correlations between their antimicrobial activity and structural/dynamic parameters. These parameters included the degree of conformational plasticity, the depth of immersion into the bi-layer, and the population of the membrane binding mode characterized by the embedding of the hydrophobic peptide pattern into the acyl chain region of lipids. In particular, the peptide [W4R5] exhibited an optimal "activity/binding to the bacterial membrane" pattern. This work highlights the significance of our multidisciplinary approach in efficiently deciphering finely regulated SAR profiles for a series of homologous peptides with diverse activities. Furthermore, this research provides a solid foundation for the rational design of novel antimicrobial peptides.

Antimicrobial peptides (AMPs) are essential components of the innate immune system, present across a spectrum of organisms. Their versatility lies in their ability to effectively inhibit a wide range of pathogens including bacteria, fungi, parasites, and viruses. As the challenge of antibiotic resistance escalates and concerns surrounding antibiotic use grow, AMPs have emerged as promising alternatives. Their applications span diverse domains such as medicine, agriculture, food production, animal husbandry, and aquaculture, primarily due to their efficacy against resistant pathogens, signifying their crucial role in combating infections. Beyond their antimicrobial properties, research illuminates their intricate involvement in the immune response network. These peptides impact crucial processes including cytokine release, chemotaxis, wound healing, angiogenesis and the activation of the adaptive immune system. This comprehensive review delves into the multifaceted realm of AMPs, encompassing their classification, varied applications across industries and notably, their significance in diverse disease conditions like infections, skin diseases, cancer, oral diseases, lung diseases and cardiovascular ailments. Special attention is directed towards current advancements in clinical applications of peptide-based therapeutics, offering invaluable insights into their potential future integration within clinical settings.

In 2020, the WHO established a road map for neglected tropical diseases 2021−2030 that aims to control and eradicate 20 diseases, including Leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions such as those caused by Trypanosoma cruzi and Leishmania spp infections. In this scenario, it is worth highlighting a group of natural peptide molecules (AMPs and CPPs) that are promising strategies for improving therapeutic efficacy against these neglected zoonoses, avoiding the development of toxicity and resistance of conventional treatments. This review presents the novelties of these peptide molecules and their ability to cross a whole system of cell membranes, as well as to stimulate the host immune defenses or even serve as a vector of molecules. The efforts of the biotechnological sector will make it possible to overcome the limitations of antimicrobial peptides through encapsulation and functionalization methods to obtain approval for these treatments to be used in clinical programs for the eradication of Leishmaniosis and Chagas disease.

Staphylococcus aureus can develop resistance by mutation, tranfection or biofilm formation. Resistance was induced in S. aureus by growth in sub-inhibitory concentrations of ciprofloxacin for 30 days. The ability of the antimicrobials to disrupt biofilms was determined using crystal violet and live/dead staining. Effects on the cell membranes of biofilm cells was evaluated by measuring release of dyes and ATP and nucleic acids. S. aureus did not develop resistance to the AMPs but resistance increased to ciprofloxacin by 128 times after 30 passages. Only peptides reduced biofilms of ciprofloxacin resistant cells. The antibiofilm effect of melimine with ciprofloxacin was more (27%) than with melimine alone at 1X MIC (p < 0.001). Similarly, at 1X MIC the combination of Mel4 and ciprofloxacin produced more (48%) biofilm disruption than Mel4 alone (p < 0.001). Combinations of either of the peptides with ciprofloxacin at 2X MIC released  66 nM ATP, more than either peptide alone (p  0.005). At 2X MIC, only melimine in combination with ciprofloxacin released DNA/RNA which was 3 times more than released by melimine alone (p = 0.043). These results suggest the potential use of melimine and Mel4 with conventional antibiotics for the treatments of S. aureus biofilms.

To combat infections on biomedical devices, antimicrobial coatings have attracted considerable attention, including coatings comprising naturally occurring antimicrobial peptides (AMPs). In this study the aim was to explore performance upon extended challenge by bacteria growing in media above samples. The AMPs LL37, Magainin 2, and Parasin 1 were covalently grafted onto a plasma polymer platform, which enables application of this multilayer coating strategy to a wide range of biomaterials. Detailed surface analyses were performed to verify the intended outcomes of the coating sequence. Samples were challenged by incubation in bacterial growth media for 5 and 20 hrs. Compared with the control plasma polymer surface, all three grafted AMP coatings showed considerable reductions in bacterial colonization even at the high bacterial challenge of initial seeding at 1x107 CFU, but there were increasing numbers of dead bacteria attached to the surface. All three grafted AMP coatings were found to be non-toxic to primary fibroblasts. These coatings thus could be useful to produce antibacterial surface coatings for biomaterials, though possible consequences arising from the presence of dead bacteria need to be studied further, and compared to non-fouling coatings that avoid attached dead bacteria.

The Third Generation Partnership Project(3GPP) has specified the Cellular Vehicle-to-Everything (C-V2X) radio access technology in Releases 14 and 15, with a focus on facilitating direct communication between vehicles through the sidelink PC5 interface. This interface offers a robust cloud-native core network with end-to-end network slicing functionality. The performance of di-rect vehicle-to-vehicle (V2V) communications has been improved by using the sidelink interface, which allows for network infrastructure by-pass. Sidelink transmissions make use of orthogonal resources that are either centrally allocated (Mode 1) or chosen by the vehicles themselves (Mode 2). The development of radio access technologies that enable dependable and low-latency vehicular communications has become of utmost relevance with the rise in interest in connected and autonomous vehicles. This is especially necessary when there are heavy traffic conditions and patterns. We thoroughly examined the New Radio (NR) sidelink’s performance under various vehicle densities, speeds, and distance settings. Thus, by evaluating sidelink’s strengths and drawbacks, we are able to optimize resource allocation to obtain maximum coverage in urban areas. The performance evaluation is conducted on Network Simulator 3 (NS3.34/5G-LENA) utilizing various network metrics such as average packet reception rate, throughput, and latency.

Keywords: Agrobacterium 1; Xenorhabdus 2; NR-AMP 3 T-DNA keyword 4; TI-plasmid 5; Intact/Cured/T-DNA Deleted 6 Sensitive/Resistant 7; EMA_PF2 8; HPLC 9

Sporothrix brasiliensis is the most pathogenic species, responsible for the Brazilian cat-transmitted sporotrichosis hyperendemics. In this scenario, investigation of pathogen-host interaction can provide relevant information for future treatment strategies. To this end, the invertebrate Galleria mellonella has proven to be a suitable alternative to evaluate the virulence of pathogenic fungi since the insect immune system is similar to the mammalian innate immune response. The aim of this work was to investigate phenotypic and molecular aspects of the immune response of G. mellonella throughout the S. brasiliensis infection. Hemocyte density and the evolution of the fungal load were evaluated. In parallel, RT- qPCR expression analysis of genes encoding antimicrobial peptides (Gallerimycin and Galiomycin) and stress management genes (C7 Contig 15362 and C8 Contig 1910) was conducted. Fungal load and hemocyte densities were proportionally increasing simultaneously to the deleterious morphological events and larvae mortality. Gallerimycin, C7 Contig 15362, and C8 Contig 19101 genes were positively regulated (p&lt;0.05) at distinct moments of S. brasiliensis infection, characterizing a time-dependent and alternately modulated profile. Galiomycin gene expression remained unchanged. Our results contribute to the future proposal of potential alternative pathways to treat and, consequently, control S. brasiliensis zoonosis, a major public Health in Latin America.

Antimicrobial peptides (AMPs) are considered as promising alternatives to conventional antibiotics in order to overcome the growing problems of antibiotic resistance. Computational prediction approaches receive an increasing interest to identify and design the best candidate AMPs prior to the in-vitro tests. In this study, we focused on the linear cationic peptides with non-hemolytic activity, which are downloaded from the Database of Antimicrobial Activity and Structure of Peptides (DBAASP). Referring to the MIC (Minimum inhibition concentration) values, we have assigned a positive label to a peptide if it shows antimicrobial activity; otherwise the peptide is labeled as negative. Here, we focused on the peptides showing antimicrobial activity against Gram-negative and against Gram-positive bacteria separately, and we created two datasets accordingly. Ten different physico-chemical properties of the peptides are calculated and used as features in our study. Following data exploration and data preprocessing steps, a variety of classification algorithms are used with 100-fold Monte Carlo Cross Validation to build models and to predict the antimicrobial activity of the peptides. Among the generated models, Random Forest has resulted in the best performance metrics for both Gram-negative dataset (Accuracy: 0.98, Recall: 0.99, Specificity: 0.97, Precision: 0.97, AUC: 0.99, F1: 0.98) and Gram-positive dataset (Accuracy: 0.95, Recall: 0.95, Specificity: 0.95, Precision: 0.90, AUC: 0.97, F1: 0.92) after outlier elimination is applied. This prediction approach might be useful to evaluate the antibacterial potential of a candidate peptide sequence before moving to the experimental studies.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Human milk reduces risk for necrotizing enterocolitis in preterm infants. Necrotizing enterocolitis occurs in the ileocecal region where thousands of milk protein-derived peptides have been released from digestion. Digestion-released peptides may exert bioactivity, such antimicrobial and immunomodulatory activities, in the gut. In this study, we applied mass spectrometry-based peptidomics to characterize peptides present in colostrum before and after in vitro digestion. Sequence-based computational modeling was applied to predict peptides with antimicrobial activity. We identified more peptides in undigested samples, yet the abundances were much higher in the digested samples. Heatmapping demonstrated highly different peptide profiles between undigested and digested samples. Four peptides (αS1-casein [157–163], αS1-casein [157–165], β-casein [153–159] and plasminogen [591–597]) were selected, synthesized and tested against common pathogenic bacteria associated with necrotizing enterocolitis. All four exhibited bacteriostatic, though not bactericidal, activities against Klebsiella aerogenes, Citrobacter freundii and Serratia marcescens, but not Escherichia coli.

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

The manuscript presents the applicability of the Gumbel distribution in the frequency analysis of extreme events in hydrology. The advantages and disadvantages of using the distribution are highlighted, as well as recommendations regarding its proper use. A literature review was also carried out regarding the methods of estimating the parameters of the Gumbel distribution. Thus, for the verification of the methods, case studies are presented regarding the determination of the maximum annual flows and precipitations using nine methods for parameter estimation. The influence of the observed data lengths on the estimation of the statistical indicators, the parameters and the quantiles corresponding to the field of low annual exceedance probabilities (p <1%) is also highlighted. The results are compared to those obtained with the Generalized Extreme Value distribution, respectively the Burr and the Wakeby distributions with parameters estimated using the L-moments. The results highlight and reaffirm the statistical, mathematical and hydrological recommendation regarding the avoidance of using the Gumbel distribution in Flood Frequency Analysis and its use with reservations in the case of maximum precipitation, especially when the statistical indicators of the analyzed data are not close to the characteristic ones and unique to the distribution.

This study focuses on the enzymatic hydrolysis of hemoglobin, the main component of cruor that gives blood its red color in mammals. The antibacterial and antioxidant potential of human hemoglobin hydrolysates were evaluated in comparison to bovine hemoglobin. The results showed strong antimicrobial activity of the peptide hydrolysates against six bacterial strains, independent of the initial substrate concentration level. The hydrolysates also showed strong antioxidant activity measured by four different tests. In addition, the antimicrobial and antioxidant activity of the human and bovine hemoglobin hydrolysates showed little or no significant difference, with only the concentration level being the determining factor in their activity. The results of the mass spectrometry study showed the presence of a number of bioactive peptides, the majority of which have characteristics similar to those mentioned in the literature. New bioactive peptides were also identified in human hemoglobin, such as antibacterial peptides PTTKTYFPHF (α37-46), FPTTKTYFPH (α36-45), TSKYR (α137-141) and STVLTSKYR (α133-141), as well as an antioxidant TSKYR (α137-141). According to these findings, human hemoglobin represents a promising source of bioactive peptides beneficial to the food or pharmaceutical industries.

Tandemly organized rRNA genes are the typical example of a multigene family, where individual members evolve coordinately within but independently between species due to gene conversion and unequal crossing over. More frequently, in eukaryotic species with an inter-species hybrid origin, expression of unhomogenized rRNA genes from one progenitor is epigenetically silenced because of nucleolus dominance, and distinct rRNA genes may lose functionality and evolve faster. Interestingly, we obtained unusual ribosomal gene sequences from Oryza species that showed great diversity and did not appear in the present rice genomic sequence. The diversity of rDNA sequences indicated that the homogenization in rice is incomplete and explains the introgression of distinct rRNA gene families into ancestral rice genome before speciation and continent separation. The divergent large subunit (LSU) ribosomal genes are expressed, some of them differentially, depending on the N-fertilization of plants. Detection of differential transcripts of the rRNA genes suggested that rRNA gene families are not functionally equivalent. Phylogenetic analysis assigned Oryza species branching order to monocots, and monocot lineages probably have the same ecological origin by molecular clock calculation. Therefore, our results suggested that the geographical distances of continents separation cause barriers to the gene flow and homogenization among Oryza species which requires further explanation,

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

Antimicrobial peptides (AMPs) are a promising alternative to antibiotics to combat drug resistance in pathogenic bacteria. However, the development of AMPs with high potency and specificity remains a challenge, and new tools to evaluate antimicrobial activity are needed to accelerate the discovery process. As a step toward direct prediction of the experimental minimum inhibitory concentration (MIC) of AMPs, we proposed MBC-Attention, a combination of a multi-branch CNN architecture and attention mechanism. Using a curated dataset of 3929 AMP against Escherichia coli, the optimal MBC-Attention model achieved an average Pearson correlation coefficient of 0.775 and an RMSE of 0.533 (log μM) in three independent tests of 393 sequences each. This results in a 5–12% improvement in PCC and 7–13% improvement in RMSE compared with RF and SVM models. Ablation studies confirmed that both attention mechanisms contributed to performance improvement.

As one of the typical deposits in Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province, the Daliangzi Pb-Zn deposit has a close genetic relation with the structural system of “black/fracture zone” formed under the action of NWW-approx. EW strike-slip structures in the metallogenic province, but the mechanism of rock and ore-controlling action of the structural system remains unclear. Based on detailed analysis of tectonite-mineralized alteration lithofacies of R1 “black/fracture zone”, the tectonite-mineralized alteration lithofacies zones can be divided into 4 types in succession outward from the Pb-Zn mineralization center, i.e., ① brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone, ② stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone, ③ veined pyrite-sulfide-dolomitic cataclasite facies zone, and ④ fine-veined calcite-black carbonized dolomite facies zone; Cl- and SO42--rich high-temperature oxidizing ore-bearing fluid mixes with reducing fluid in Zone ① while migration and precipitation occur in Zone ④. With the evolution of ore-forming fluid, the homogenization temperature decreases from Zone ① to Zone ④, the salinity increases from Zone ① to Zone ② and then decreases to Zones ③ and ④, and the fluid density has little change on the whole; the contents of Zn, Pb, Cu, Ga, Ge, Cd, Ag, and other metallogenic elements, the Zn/Pb ratio, and the CaO/MgO mole ratio decrease gradually from Zone ① to Zone ④; and REE fractionation, calcilization, silicification, and pyritization enhance gradually from Zone ① to Zone ④. This series of changes are the product of diapirism (cryptoexplosion) of strike-slip structures and “black/fracture zone”, among which the second-order structures (F5, F100, and other faults) derived from NWW-approx. EW striking dextral shear-tension faults F1 and F15 control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones. Therefore, this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of “black/fracture zone” and proposes that Zones ① and ② are important prospecting criteria. conclusions.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both hereditary and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variations that can be transmitted from one generation to another can be a significant contributor to causing family or isolated DCM. Genetic variation also plays a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a diverse range of phenotypic expressions. It is crucial to select the most probable patients to have advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the crucial relationships between genotype and phenotype, and the usefulness of genetic testing in the therapeutic care of both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versa-tile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for under-standing the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other, non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer’s, neurodegenerative disorders, Wilson's, and Menkes disease. Certain metal com-plexes have potential applications as radiopharmaceuticals. The examination of these complexes was done by preforming UV-Vis, IR, EPR, NMR spectroscopy, and X-ray analysis.

Ribosomal proteins (r-proteins) are abundant, highly conserved, and multifaceted cellular proteins in all domains of life. Most r-proteins have RNA-binding properties and are able to form protein-protein contacts. Bacterial r-proteins govern the co-transcriptional rRNA folding during ribosome assembly and participate in formation of the ribosome functional sites such as the mRNA binding site, tRNA binding sites, the peptidyl- transferase center, and the protein exit tunnel. In addition to their primary role in a cell as integral components of the protein synthesis machinery, many of r-proteins can function beyond the ribosome (the phenomenon known as moonlighting), acting either as individual regulatory proteins or in complexes with various cellular components. Extraribosomal activities of r-proteins have been intensively studied over decades (reviewed in [1]). The past decade brought significant advancement in our knowledge of r-protein functions due to expanding studies on ribosomes and gene expression mechanisms not only in model bacteria like Escherichia coli or Bacillus subtilis, but also in previously little-explored bacterial species from various phyla. This review is aimed to update the information on multiple functions of r-proteins in bacteria.

We tested the hypothesis that concatemers of ancestral tRNAs gave rise to the 16S ribosomal RNA. We built an ancestral sequence of proto-tRNAs that showed a significant identity of 51.69% and a percentage of structural identity of 0.941 with the 16S ribosomal molecule. We also propose a hypothesis for the emergence of translation.

After a survey on polymer plasticization theories and conventional criteria to evaluate polymer-plasticizer compatibility through the solubility parameter, an attempt to create a polymer-plasticizers polarity scale through solvatochromic dyes has been made. Since the Reichardt’s ET(30) dye is insoluble in rubber hydrocarbon polymers like polyisoprene, polybutadiene and styrene-butadiene copolymers and is not also useful for the evaluation of the hydrocarbons and ester plasticizers, the Nile Red solvatochromic dye was instead used extensively and successfully for this class of compounds. A total of 53 different compounds were evaluated with the Nile Red dye and wherever possible also with the ET(33) Reichardt’s dye. A very good correlation was then found between the Nile Red scale E(NR) and the Reichardt’s ET(30) scale for this class of compounds focusing on diene rubbers and their typical hydrocarbons and new esters plasticizers. Furthermore, the E(NR) scale shows also a reasonable correlation with the total solubility parameter calculated according to the Van Krevelen method. Based on the above results, some conclusion was made about the compatibility between the diene rubbers and the conventional plasticizers as well as some new and green plasticizer proposed for the rubber compounds.

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.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

This research explores the development of thermoplastic vulcanizate (TPV) blends derived from natural rubber (NR) and ethylene-butene copolymer (EBC) using a specific blend ratio and melt mixing technique. A comprehensive full factorial design of experiments (DOE) methodology is employed to optimize the processing parameters. TPVs are produced through dynamic vulcanization, combining rubber crosslinking and melt blending within a thermoplastic matrix under high temperatures and shear. The physico-mechanical properties of these TPVs are then analyzed. The objective is to enhance the mechanical performance by assessing the influence of blend ratio, mixing temperature, rotor speed, and mixing time on crucial properties, including tensile strength, elongation at break, compression set, tear strength, and hardness. Analysis of variance (ANOVA) identifies the optimal processing conditions that significantly improve material performance. Validation is achieved through atomic force microscopy (AFM), confirming the phase-separated structure and thus a success of dynamic vulcanization. Rubber process analyzer (RPA) and dynamic mechanical analyzer (DMA) assessments provide insights into the viscoelastic behavior and dynamic mechanical responses. Deconvolution analysis of temperature-dependent tanδ peaks reveals intricate microstructural interactions influencing the glass transition temperature (Tg). The optimized TPVs exhibit enhanced stiffness and effective energy dissipation capabilities across a wide temperature range, making them suitable for applications demanding thermal and mechanical load resistance. This study underscores the pivotal role of precise processing control in tailoring the properties of NR/EBC TPVs for specialized industrial uses. It highlights the indispensable contribution of the DOE methodology to TPV optimization, advancing material science and engineering, particularly for industries requiring robust and flexible materials.

The ribosome is a macromolecular complex composed of RNA and proteins that interact through an integrated and interconnected network to preserve its ancient core activities. In this review, we emphasize the pivotal role played by RNA-binding proteins as a driving force in the evolution of the current form of the ribosome, underscoring their importance in ensuring accurate protein synthesis. This category of proteins includes both ribosomal proteins and ribosome biogenesis factors. Impairment of their RNA-binding activity can also lead to ribosomopathies, a group of disorders characterized by defects in ribosome biogenesis that are detrimental to protein synthesis and cellular homeostasis. A comprehensive understanding of these intricate processes is essential for elucidating the mechanisms underlying the resulting diseases and advancing potential therapeutic interventions.

"Industry 5.0” is the latest industrial revolution. A variety of cutting-edge technologies, including artificial intelligence, the Internet of Things (IoT), and others, come together to form it. This new era will bring about significant changes in the way businesses operate, allowing them to become more cost-effective, more efficient, and produce higher-quality goods and services. Because sen-sors are getting better, 5G networks are being put in place, and more industrial equipment and machinery are becoming available, the manufacturing sector is going through a significant period of transition right now. These newly scalable opportunities make it possible to use and spread blockchain architectures on the shop floor, which is made possible by the ever-decreasing costs associated with implementing blockchain technology. Even though modern production models make use of the cloud (both internal and external services), networks and systems can take ad-vantage of the cloud's relatively low cost, scalability, increased computational power, real-time communication, and data transfer capabilities to create much smarter and more autonomous systems. This paper presents the results of an investigation into how blockchain services for large-scale industry networks could benefit from increased levels of security, transparency, and efficiency. We discuss the ways in which decentralized networks that make use of protocols and meshes might make things better with these technologies, which are not going away anytime soon. We emphasize the significance of new design in regards to cybersecurity, data integrity, and storage by using straightforward examples that have the potential to lead to the excellence of distributed systems.

Various techniques to tackle the black hole information paradox have been proposed. A new way out to tackle the paradox is via the use of pseudo-density operator. This approach has successfully dealt the problem with a two-qubit entangle system for a single black hole. In this paper, we present the interaction with a binary black hole system by using an arrangement of the three-qubit system of Greenberger–Horne–Zeilinger (GHZ) state. We show that our results are in excellent agreement with the theoretical value. We have also studied the interaction between the two black holes by considering the correlation between the qubits in the binary black hole system. The results depict a complete agreement with the proposed model. In addition to the verification, we also propose how modern detection of gravitational waves can be used on our optical setup as an input source, thus bridging the gap with the gravitational wave’s observational resources in terms of studying black hole properties with respect to quantum information and entanglement.

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide–membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

In recent years, there has been an increasing interest in adopting novel sensing technologies for the continuous monitoring of structural systems. In this respect, Micro-Electro-Mechanical System (MEMS) sensors are widely used in several applications, including Structural Health Monitoring (SHM). Thanks to their significantly lower cost, ease of installation on the structure, and lower power consumption, they enable extensive, pervasive, and battery-less monitoring systems. This paper presents an innovative high-performance device for SHM applications, based on a low-noise triaxial MEMS accelerometer, providing a guideline and insightful results about the opportunities and capabilities of these devices. Sensor nodes have been designed, developed, and calibrated to meet structural vibration monitoring and modal identification requirements. These components include a protocol for reliable command dissemination through the network and data collection, and improvements to software components for data pipelining, jitter control, and high-frequency sampling. Devices were tested in the lab using shaker excitation. Results demonstrate that MEMS-based accelerometers are a feasible solution to replace expensive piezo-based accelerometers. Deploying MEMS is promising to minimize sensor node energy consumption. Time and frequency domain analysis show that MEMS can correctly detect modal frequencies, useful parameters for damage detection. The acquired data from the test bed were used to examine the functioning of the network, data transmission, and data quality. The proposed architecture has been successfully deployed in a real case study to monitor the structural health of the Marcus Aurelius Exedra Hall within the Capitoline Museum of Rome. The performance robustness was demonstrated and the results showed that the wired sensor network provides dense and accurate vibration data for structural continuous monitoring.

Since the 1970s, the application of microprocessor in industrial machinery and the development of computer systems have transformed the manufacturing landscape. The rapid integration and automation of production systems have outpaced the development of suitable human design criteria, creating a deepening gap where human factor was seen as an important source of errors and disruptions. Today the situation seems different: the scientific and public debate about the concept of Industry 4.0 has raised the awareness about the central role humans have to play in manufacturing systems, to the design of which they must be considered from the very beginning. The future of industrial systems, as represented by Industry 4.0, will rely on the convergence of several research fields such as Intelligent Manufacturing Systems (IMS), Cyber-Physical Systems (CPS), Internet of things (IoT), but also socio-technical fields such as social approaches within technical systems. This article deals with different Human dimensions associated with CPS and IoT and focuses on their conceptual evolution of automatization to improve the sociability of such automated production systems and consequently puts again the human in the loop. Hereby, our aim is to take stock of current research trends, and to show the importance of integrating human operators as a part of a socio-technical system based autonomous and intelligent products or resources. As results, different models of sociability as way to integrate human into the broad sense and/or the development of future automated production systems, were identified from the literature and analysed.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Despite several decades of research, the physics underlying translation – protein synthesis at the ribosome – remains poorly studied. For instance, the mechanism coordinating various events occurring in distant parts of the ribosome is unknown. Very recently, we have suggested that this allosteric mechanism could be based on the transport of electric charges (electron holes) along RNA molecules and localization of these charges in the functionally important areas; this assumption was justified using tRNA as an example. In this study, we turn to the ribosome and show computationally that holes can also efficiently migrate within the whole ribosomal small subunit (SSU). The potential sites of charge localization in SSU are revealed, and it is shown that most of them are located in the functionally important areas of the ribosome – intersubunit bridges, Fe4S4 cluster and the pivot linking the SSU head to the body. As a result, we suppose that hole localization within the SSU can affect intersubunit rotation (ratcheting) and SSU head swiveling, in agreement with the scenario of electronic coordination of ribosome operation. We anticipate that our findings will improve the understanding of the translation process and advance the molecular biology and medicine.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

Actuated carbon (AC) is utilized in various conditions of uses after its disclosure as a solid and dependable adsorbent. A review on AC is introduced along with returning to the wellsprings of AC age; strategies used to produce AC including pyrolysis enactment; actual actuation; synthetic initiation and steam pyrolysis. The significant variables influencing the AC creation, the potential uses of AC and their future possibilities are likewise examined. AC is applied in water, wastewater and leachate medicines in numerous nations, particularly to clean the shading, eliminate the smell and some substantial metals. Taking into account this, an exhaustive rundown of research on compound, physical and organic change strategies of initiated carbon relating to prevent of foreign substance expulsion from watery arrangements was aggregated and investigated. Additionally, the examination of the actual blending strategy and the impregnation technique in enactment with antacid metals shows that the actuated carbon got through actual blending had a higher porosity than the initiated carbon created by the impregnation technique. The uses of initiated carbon items were quickly surveyed.

Gap junctions (GJ) and connexins play integral roles in cellular physiology and have been found to be involved in multiple pathophysiological states from cancer to cardiovascular disease. Studies over the last 60 years have demonstrated the utility of altering GJ signaling pathways in experimental models, which has led to them being attractive targets for therapeutic intervention. A number of different mechanisms have been proposed to regulate GJ signaling, including channel blocking, enhancing channel open state, and disrupting protein-protein interactions. The primary mechanism for this has been through the design of numerous peptides as therapeutics, that are either currently in early development or are in various stages of clinical trials. Despite over 25 years of research into connexin targeting peptides, the overall mechanisms of action are still poorly understood. In this overview, we discuss published connexin targeting peptides, their reported mechanisms of action and the potential for these molecules in the treatment of disease.

We report the isolation of two novel degrading bacterial strains active against the potential environmental pollutant acetamino-phen/paracetamol. Streptomyces Chrestomyceticus (RS2) and Streptomyces Flavofuscus (M33) collected from El-Natrun Valley, Egypt, water, sediment, and sand samples were taxonomically characterized via conidiophores morphologic characterization under Trans-mission Electron Microscope (TEM). Genotypic identification, done based on their 16S rRNA gene sequence analysis followed by BLAST alignment and deposited on the NCBI as 2 novel strains. The phylogenetic tree was constructed using an appropriate software. Acetaminophen degradation-products chemical structure was identified by GC/LC MS. The biological antimicrobial activity of some selected acetaminophen degradation-products extracts and derived compounds was examined against panel of test micro-organisms and found to be have high anti-microbial effect. In addition, in silico cheminformatics Swiss ADMET evaluation of these selected deg-radation extract for gastric absorption, distribution, hepatic metabolism, renal excretion as well as distribution to CNS and finally not mutagenic/teratogenic or genotoxic virtually. In vitro cytotoxic activity of these selected bio-degradation products was performed against HepG2 and MCF7 cancer cell lines, revealing that M33 and RS2 extract effect on acetaminophen/paracetamol bio-degradation products are potentially safe with higher IC50 on HepG2 and MCF7, in comparison to acetaminophen/paracetamol with IC50 of 108.5 μg/ml. Moreover, the in vivo acute oral single dose toxicity experiment was conducted, being compared with acetamino-phen/paracetamol to confirm that the bio-degradation products have lower toxicity than acetaminophen in vivo and in silico.

Lipoxygenases are non-heme iron-containing enzymes that catalyze the oxidation of polyunsaturated fatty acids, resulting in the production of lipid hydroperoxides, which are precursors of inflammatory lipid mediators. The enzymes are widely distributed in humans, other eukaryotes, and cyanobacteria. Lipoxygenases hold promise as therapeutic targets for several human diseases, including cancer and inflammation-related disorders. Inhibitors of lipoxygenase have potential applications in pharmaceuticals, cosmetics, and food. Bioactive peptides are short amino acid sequences embedded within parent proteins, which can be released by enzymatic hydrolysis, microbial fermentation, and gastrointestinal digestion. A wide variety of bioactivities have been documented for protein hydrolysates and peptides derived from different biological sources. Recent findings indicate that protein hydrolysates and peptides derived from both edible and non-edible bioresources can act as lipoxygenase inhibitors. In this review, we explore current knowledge on the production of anti-lipoxygenase protein hydrolysates and peptides from millet grains, chia seeds, insects, milk proteins, fish feed, velvet antler blood, fish scales, and feather keratins. We delve into the anti-lipoxygenase activities and modes of action of these protein hydrolysates and peptides, while also highlighting the strengths and shortcomings of previous research. Additionally, we propose potential research directions and areas of improvement that can propel the discovery of anti-lipoxygenase peptides in the near future.

Description of a novel bovine antimicrobial peptide and its antimicrobial spectrum. RNA isolation and RT-PCR were done from various tissues. DCD peptide was synthesized, and antimicrobial activity was analyzed. Bovine dermcidin gene contains five exons intermittent by 4 introns. Bovine DCD-mRNA was 398 bp with ORF 336 bp. Bovine DCD was expressed in skin and blood. Analysis of the amino acid compositions revealed that cysteine was repeated 6 times indicating the presence of 3 disulfide bonds that play role in the peptide stability. Staphylococcus epidermidis, Streptococcus bovis, and Enterococcus faecalis were affected by Bovine DCD peptide. Highest antimicrobial effect was at 50 and 100 µg/ml. The effect on Escherichia coli and Candida albicans was slightly low. In all bacteria, Bovine DCD peptide activity did not affect by varying pH values, but in Staphylococcus aureus, the activity was affected greatly at pH 4.5 and 5.5. The optimum salt concentrations were 100 and 50 mM NaCl with all bacterial strains and E. coli, respectively. In case of C. albicans, the antimicrobial activity of Bovine DCD peptide decreased with increasing the pH value regardless the NaCl concentration. The pH 6.5 of the sweat buffer was the optimum for the Bovine DCD peptide activity.

Meat serves as a vital component of the human diet, offering a rich source of protein and essential trace elements. China stands as both a significant producer and consumer of meat on a global scale, leading the world in terms of total meat production and consumption. As the standard of living within the country continues to rise, there is a growing emphasis on the nutritional value and safety of meat consumption. The tenderness of meat is a critical factor influencing its overall quality. Traditionally, tenderness has been assessed through shear force testing, a method that is inherently destructive, inefficient, and results in considerable sample wastage. In light of these drawbacks, non-destructive testing techniques have emerged as a preferred alternative, promising greater accuracy, efficiency, and convenience without compromising the integrity of the samples. This paper delves into the application of five advanced non-destructive testing technologies in the realm of meat tenderness assessment. These include near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, airflow optical fusion detection, and nuclear magnetic resonance detection. Each technology is scrutinized for its respective strengths and limitations, providing a comprehensive overview of their current utility and potential for future development. Moreover, the integration of these techniques with the latest advancements in artificial intelligence (AI) technology is explored. The fusion of AI with non-destructive testing offers a promising avenue for the development of more sophisticated, rapid, and intelligent systems for meat tenderness evaluation. This integration is anticipated to significantly enhance the efficiency and accuracy of quality assessment in the meat industry, ensuring a higher standard of safety and nutritional value for consumers. The paper concludes with a set of technical recommendations aimed at guiding the future direction of non-destructive, AI-enhanced meat tenderness detection, thereby contributing to the ongoing improvement of the meat industry in China and beyond.

The pharmaceutical industry usually utilizes either hydrophobic or hydrophilic substances extracted from raw plant materials for preparing a final product, However, the plant material waste still contain substances with an opposite solubility. The aim of this study was to enhance the comprehensive usability of plant materials by developing a new non-wasting extraction method for eucalypt leaves and by investigating the phytochemical and pharmacological properties of eucalypt extracts and their 3D-printed dosage forms. The present extraction method enabled to prepare both hydrophobic soft extracts and hydrophilic (aqueous) dry extracts. We identified total 28 terpenes in the hydrophobic soft extract. In the hydrophilic dry extract, total 57 substances were identified, and 26 of them were successfully isolated. The eucalypt extracts studied showed a significant antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Corynebacterium diphtheriae gravis, and Corynebacterium diphtheriae mitis. The anti-inflammatory activity of the dry extract was studied with a formalin oedema model in mice. The maximum anti-exudative effect of the dry extract was 61.5% at a dose of 20 mg/kg. The composite gels of polyethylene oxide and eucalypt extract were developed, and the key process parameters for semi-solid extrusion (SSE) 3D printing of such gels were verified. The SSE 3D-printed preparations of novel synergistically acting eucalypt extracts could have uses in antimicrobial and anti-inflammatory medicinal applications.

Streptococcal infection is a main infectious diseases for farmed grey mullet (Mugil cephalus). This study were to identify spreptococcal species in diseased farmed grey mullet and to investigate differences in susceptibility to 13 antibiotics and in genotypes between the stains from the grey mullet and non-grey mullet. 170 samples from diseased farmed grey mullet were collected from three county in 2013 -2016. Multiplex PCR identified L. garviea (146) as the main pathogen, S. agalactia (9), S. dysgalactiae (19), and double infection (5), but no S. iniae. The prevalence changed annually and differed among three counties. Pulsed-field gel electrophoresis (PFGE) analysis demonstrated identical genotype with an ApaI-digested DNA pattern. Disc diffusion results demonstrated differences in antibiotic susceptibility between the strains from grey mullet (146) and non-grey mullet (30). Almost all strains resisted to clindamycin and all strains were susceptible to six antibiotic in grey mullet and 4 antibiotics in non-grey mullet. The reduced susceptible strains was more in non-grey mullet than grey mullet group. The reduced susceptible strains were observed the highest in 2014 and in Chiayi county and decreased from 2014 to 2016. However, the strains with reduced susceptibility to ceftriaxone, cirpofoxacin, moxifloxacin, tetracycline for human treatment were observed.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

Whether the different NR-AMPs could ever be utilized as drugs not only against prokaryotic (bacteria) pathogens but eukaryotic (fungal pathogens, and parasitic protists) depends on the side effects. To get experimental experience about the option of applying EPB-produced antimicrobials to pathogens, and parasites of veterinary significance, we present here the results of an in vitro, and an accompanying in vivo study on chicken. In the in vitro study, we tested the cytotoxic potential of the cell-free conditioned culture media (CFCM) of three entomopathogenic bacterium species, - X. budapestensis, DSM16342 (EMA); X. szentirmaii DSM16338 (EMC); Photorhabdus luminescens ssp. akhurstii TT01 - on chicken tissue culture cells, namely, on the Leghorn Male Hepatoma (LMH), [92] cells, (a permanent confluent hepato-carcinoma cell line). Each CFCM proved rather cytotoxic in this test. In the in vivo study, we fed freshly hatched male broiler chickens for 42 days with XENOFOOD [39] which contained autoclaved cultures of EMA, and EMC). These bacteria were grown on standard chicken (starter and grower) [HM3] [u4] feed, and the whole culture was used as a “food supplement”. [HM5]. It had been known that these EPB species cannot grow that is, not viable) atbody temperature (above 33 C).

Hydrogen is believed to be the principal domain of sustainable energy drive as an alternative to fossil fuels. Unlike the existing standards and knowledge for other fuels, the integrity of sealing and storage materials under the hydrogen environment is not comprehensively studied due to the comparatively new technology and lack of standard laboratory protocols. Typically, storage and polymer materials used as sealing experience degradation and damage in different ways over time in the exposure of hydrogen at different operating conditions, called aging. Improved understanding of the physical and chemical mechanism of degradation due to gaseous hydrogen atmosphere; helps to select and develop the materials best suited to carrier and sealing for respective applications. Damage to materials from aging is inevitable in high-pressure hydrogen gas exposure. This review discusses the mechanism of different categories of aging of storage and sealing materials under the hydrogen environment. Also, the article approaches discussing different laboratory test methods for each type of aging simulation. It covers the limitation of current research on determining material integrity through existing techniques of aging experiments and also explores the latest development. Important improvements are suggested in terms of materials development and testing procedures to meet the existing knowledge in the literature.

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR-type 2 angiogenesis and vascular morphogenesis as the tyrosin kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between vascular endothelial growth factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and is shared by stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.

Since their identification over twenty-five years ago, the plethora of cell penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid long peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger then themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell activated forms. These methods are currently being used to image integrin expressing tumors, breast cancer cells, human histiocytic lymphoma and protease secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, anti-tumor antibodies and nanoparticles can be functionally attached to these peptides leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research leading to identification of CPPs with a comprehensive state of the art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

It is claimed that classical mechanics (CM) in terms of its equivalent Koopman-von Neumann formulation (KvN) is indeed a ’real’ quantum theory since the formalism of quantum mechanics (FQM) does not, nor need it, exclude it as a such. This claim is made manifest by suggesting a common structure of which both KvN and ordinary quantum mechanics (OQM) correspond to unitary representations of, although unitarily inequivalent such. It is shown that OQM is obtained by enforcing the extra physical condition of quantized energy levels, which by itself does not constitute the ’quantum mystery’. It is furthermore shown that KvN in a physically realizable sense contain the hallmark quantum behavior of quantum interference. It is hence concluded that both CM and OQM are subjected to the same foundational issues. As the central part of both KvN and OQM is the introduction of probabilities via FQM it is suggested that the foundational issues regarding FQM are less about FQM itself and more about the concept of probability.

Europium is one of the most reactive lanthanides and humans use it in many different applica-tions, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) were obtained and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothi-oneins and/or displace essential cations of these proteins during their homeostasis function. Both lipid metabolism (lipid droplets that fuse with europium-containing vacuoles) and au-tophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Healthy aging among older adults requires the maintenance of good physical and cognitive activity. However, in the natural course of aging, older adults usually experience a decline in their physical and cognitive activity, causing an increasingly sedentary lifestyle. Some older adults may not have a choice but to become increasingly sedentary as they age due to injury or deteriorated physicality. As such they require a manner of assistive technologies to aid in their daily lives and activities to maintain healthy cognitive function. Social Robots are a newer form of assistive technology, specifically designed for social interactions and gameplay. As with other assistive technologies, compliance barriers to the acceptance and use of social robots and types of meaningful, seated activities among older adults are expected. To better explore this phenomenon, improve quality of life and understand what drives older adults to accept and use newer forms of technology like social robots, this research conjoins two conceptual frameworks: The Activity Theory of Aging (ATA) and the Unified Theory of Acceptance and Use of Technology (UTAUT). As social robots hold great promise for improving the quality of life for older adults, exploring what driving factors could enable their greater acceptance and use is essential to furthering this field of study within Australia.

Increased smart devices in various industries is creating numerous sensors in each of the equipment prompting the need for methods and models for sensor data. Current research proposes a systematic approach to analyze the data generated from sensors attached to industrial equipment. The methodology involves data cleaning, preprocessing, basics statistics, outlier, and anomaly detection. Present study presents the prediction of RUL by using various Machine Learning models like Regression, Polynomial Regression, Random Forest, Decision Tree, XG Boost. Hyper Parameter Optimization is performed to find the optimal parameters for each variable. In each of the model for RUL prediction RMSE, MAE are compared. Outcome of the RUL prediction should be useful for decision maker to drive the business decision; hence Binary classification is performed, and business case analysis is performed. Business case analysis includes the cost of maintenance and cost of non-maintaining a particular asset. Current research is aimed at integrating the machine intelligence and business intelligence so that the industrial operations optimized both in resource and profit.

Epstein-Barr virus (EBV)-encoded RNAs (EBERs) are structurally conserved small, noncoding RNAs constitutively expressed in EBV infection. Although primarily localised in the nucleus, EBERs are found in the cytoplasm and exosomes. However, the mechanism(s) of EBERs transport is not known. This study aimed to investigate the structural impact of EBER1 on its transport. EBER1 stem-loop (SL) deletion mutants (ΔSL1, ΔSL3 and ΔSL4) were created and stably transfected into HEK293T cells. The expression of EBER1 was quantified in total cell, nuclear, cytoplasmic and exosomal fractions. The quantification was performed in the presence of physiological expression of RPL22 and La, and after silencing them. These proteins are believed to be involved in EBER1 transport and secretion. Compared to the wildtype EBER1 transfectants, the expression level of EBER1 gene in all mutants was significantly lower in the total cell, cytoplasmic and exosomal fractions. However, ΔSL3 mutant showed significant nuclear retention. Silencing RPL22 resulted in increased nuclear-cytoplasmic trafficking of EBER1. Silencing La protein did not affect EBER1 secretion. Alternatively, the store-operated intracellular Ca2+ was found to correlate with EBER1 expression in exosomes. Taken together, EBER1 structure and its interaction with RPL22 appeared to be important in the nuclear-cytoplasmic transport of the RNA.

Small peptides (SPs), ranging from 5 to 100 amino acids, play integral roles in plants due to their diverse functions. Despite their low abundance and small molecular weight, SPs intricately regulate critical aspects of plant life, including cell division, growth, differentiation, flowering, fruiting, maturation, and stress responses. As vital mediators of intercellular signaling, SPs have garnered significant attention in plant biology research. This comprehensive review delves into SPs' structure, classification, and identification, providing a detailed understanding of their significance. Additionally, we summarize recent findings on the biological functions and signaling pathways of prominent SPs that regulate plant growth and development. The review also offers a forward-looking perspective on future research directions in peptide signaling pathways.

Antimicrobial peptides (AMPs) are promising tools for combating microbial resistance. However, their therapeutic potential is hindered by two intrinsic drawbacks – low target affinity and poor in vivo stability. Macrocyclization, a process that improves the pharmacological properties and bioactivity of peptides, can address these limitations. As a result, macrocyclic peptides represent attractive drug candidates. Moreover, many drugs are macrocycles that originated from natural product scaffolds, suggesting that nature offers solutions to the challenges faced by AMPs. In this review, we explore natural cyclic peptides from the DBAASP database. DBAASP is a comprehensive repository of data on antimicrobial/cytotoxic activities and structures of peptides. We analyze the data on small (≤25 AA) ribosomal and non-ribosomal cyclic peptides from DBAASP according to their amino acid composition, bonds used for cyclization, targets they act on, and mechanisms of action. This analysis will enhance our understanding of the small cyclic peptides that nature has provided to defend living organisms.

Small peptides are an important component of the vertebrate immune system. They are important molecules for distinguishing proteins that originate in the host from proteins derived of a pathogenic organism, such as a virus or bacterium. Consequently, these peptides are central for the vertebrate host response to intracellular and extracellular pathogens. Computational models for prediction of these peptides have been based on a narrow sample of data with an emphasis on the position and chemical properties of the amino acids. In past literature, this approach has resulted in higher predictability than models that rely on the geometrical arrangement of atoms. However, protein structure data from experiment and theory are a source for building models at scale, and, therefore, knowledge on the role of small peptides and their immunogenicity in the vertebrate immune system. The following sections introduce procedures that contribute to theoretical prediction of peptides and role in immunogenicity. Lastly, deep learning is discussed as it applies to immunogenetics and the acceleration of knowledge by a capability for modeling the complexity of natural phenomena.

During last decades multiple therapeutic approaches have been explored for improved management of peritoneally disseminated malignancies – a grim condition known as peritoneal carcinomatosis (PC). Intraperitoneal administration can be used to achieve elevated local concentration and extended half-life of the drugs in the peritoneal cavity to improve their anticancer efficacy. However, IP-administered chemotherapeutics have a short residence time in the IP space, and are not tumor selective. An increasing body of work suggests that functionalization of drugs and nanoparticles with targeting peptides increases their peritoneal retention and provides a robust and specific tumor binding and penetration that translates into improved therapeutic response. Here we review a progress in affinity targeting of intraperitoneal anticancer compounds, imaging agents and nanoparticles with tumor homing peptides. We review classes of tumor homing peptides relevant for PC targeting, payloads for peptide-guided precision delivery, applications for targeted compounds and the effects of nanoformulation of drugs and imaging agents on affinity-based tumor delivery.

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main basis of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists’ awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convienience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed good understanding about the causes of antimicrobial resistance. The most important causes reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, including organizational obstacles, resources obstacles, and personal obstacles. As a conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

Recent analyses of cosmic microwave background surveys have revealed hints that there may be a non-trivial running of the running of the spectral index. If future experiments were to confirm these hints, it would prove a powerful discriminator of inflationary models, ruling out simple single field models. We discuss how isocurvature perturbations in multi-field models can be invoked to generate large runnings in a non-standard hierarchy, and find that a minimal model capable of practically realising this would be a two-field model with a non-canonical kinetic structure. We also consider alternative scenarios such as variable speed of light models and canonical quantum gravity effects and their implications for runnings of the spectral index.

Selenocyanates form an interesting class of organic selenium compounds as they serve as multifunctional agents (being the precursors of seleninic acids and diselenides in synthetic chemistry and as antimicrobial and cytotoxic agent in biology) and, due to their similarity with better known thiocyanates promise high biological activity. Yet whilst selenocyanates are common in synthetic chemistry, they are rarely considered in pharmaceutical design. Arylmethyl selenocyanates (1-13) have been synthesized and an insight into their structural properties using X-ray crystallography has been obtained. The compounds subsequently have been evaluated for their potential antimicrobial, nematicidal and cytotoxic activity. ADMET properties in vitro, using mutagenicity (AMES) and permeability (PAMPA) tests, have been determined. The compounds exhibit pronounced activity against various strains of bacteria (both Gram-positive and Gram-negative) and yeasts. Among them, benzylselenocyanate (1) represents the most active anti-ESKAPE agent, with potent antibacterial activity, especially against multidrug resistant MRSA strains (HEMSA 5). Our results demonstrate that the arylmethyl selenocyantes are not only non-mutagenic but also possess moderate cytotoxic activity against cancer cells.

Indigo leaves form various plant species are sources of dyes/pigments, not fully exploited for making sustainable textiles. Blue indigo vat dye extracted from indigo leaves, yields high wash colorfastness but fades slowly with light, and is not easily used for direct printing. Indigo leaves can be used to produce textiles of various color shades, while light resistant Mayan-inspired hybrid pigments have not yet been used for textile coloring. Using blue indigo dyes from 3 plant species, with exhaustion dyeing, intense wash resistant blue colored textiles are produced, and in the case of Indigofera Persicaria tinctoria, textiles have antibacterial activity against S. Epidermis and E. Coli.100% Natural Mayan-inspired blue indigo pigment, made from Sepiolite clay and indigo dye, was used both in powdered and paste forms to perform pigment textile dyeing by pad cure process, and direct screen printing on textiles. A water-based bio-binder (40%) was used efficiently for both padding and printing. Bio-based Na Alginate thickener allowed color fast printing on both polyester and cotton fabrics, while bio-based glycerin allowed good print color fastness on polyester only, yielding prints with excellent color fastness to wash (5/5), to dry and wet rubbing (5/5) and light (7/7).

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Dermal penetration is considered to mainly occur via passive diffusion. Therefore, a high concentration gradient of dissolved active ingredient between formulation and skin is needed to achieve an effective dermal penetration. The concentration gradient between formulation and skin can be changed by changing the amount of dissolved active ingredient in the formulation. In case of poorly soluble active ingredients this can be achieved by using nanosized drug material instead of larger sized material. The smaller size and the resulting larger surface increase the kinetic solubility and thus increase the concentration gradient of dissolved active ingredient between formulation and skin, which then results in an increased dermal penetration. In this study we demonstrated that the concentration gradient between formulation and skin can also be influenced by the number of particles being present in the formulation and by the dose (volume of formulation) applied to the skin. Particles of undissolved active ingredient are known to act as a reservoir by releasing dissolved molecules in the liquid phase of the formulation. It could now be demonstrated that the particles - once the liquid in which they are dispersed evaporates - can connect to the skin via an aqueous meniscus. The aqueous meniscus contains dissolved active ingredient and therefore creates a small local spot with a locally high concentration gradient and improved dermal penetration. Therefore, the dermal penetration can be increased with formulations that contain high amounts of particles. This can be achieved by applying formulations with high numbers of particles and/or by applying larger volumes of particle containing formulations to the skin.

A simulation test system for the two-dimensional (2D) fuze overload loading process was designed to address the loading issues of recoil overload and centrifugal overload in fuze safety and arming (S&amp;A) devices. By incorporating centrifuge rotation energy storage, impact acceleration simulation, and equivalent centrifugal rotation simulation, a block equipped with a fuze S&amp;A device was accelerated instantly upon being impacted by a centrifuge-driven impact hammer, simulating recoil overload loading. The impact hammer was retracted instantaneously by adopting an electromagnetic brake, which resulted in the centrifugal rotation of the block around its track, to simulate the centrifugal overload loading. The dynamic equations of the simulation test system and the equations of impact hammer motions were established, whereby the rotation speed of the centrifuge and the braking force of the electromagnetic brake were calculated and selected. A dynamic model of the collision between the impact hammer and block was established using ANSYS/LS-DYNA software for simulation analysis. The acceleration curves of the recoil overload and centrifugal overload with variations in the centrifuge speed, cushion material, and buffer thickness were obtained, which verified the feasibility of the proposed loading simulation method. 2D overload loading simulation tests were performed using the developed simulation system, and the acceleration curves of the recoil overload and centrifugal overload were measured. The test results indicated that the proposed system can accomplish 2D overload loading simulations for a recoil overload of several 10000 g and centrifugal overload of several 1000 g.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

Blockchain technology has been gaining great interest from a variety of sectors including healthcare, supply chain, and cryptocurrencies. However, Blockchain suffers from its limited ability to scale (i.e. low throughput and high latency). Several solutions have been proposed to tackle this. In particular, sharding proved that it is one of the most promising solutions to Blockchain’s scalability issue. Sharding can be divided into two major categories: (1) Sharding-based Proof-of-Work (PoW) Blockchain protocols, and (2) Sharding-based Proof-of-Stake (PoS) Blockchain protocols. The two categories achieve good performances (i.e. good throughput with a reasonable latency), but raise security issues. This article focuses on the second category. In this paper, we start by introducing the key components of sharding-based PoS Blockchain protocols. Then, we briefly introduce two consensus mechanisms, namely PoS and practical Byzantine Fault Tolerance (pBFT), and discuss their use and limitations in the context of sharding-based Blockchain protocols. Next, we provide a probabilistic model to analyze the security of these protocols. More specifically, we compute the probability of committing a faulty block and measure the security by computing the number of years to fail. Finally, we evaluate the effectiveness of the proposed model via numerical analysis.

A reliable and efficient rail track defect detection system is essential for maintaining rail track integrity and avoiding safety hazards and financial losses. Eddy current (EC) testing is a non-destructive technique that can be employed for this purpose. The trade-off between spatial resolution and lift-off should be carefully considered in practical applications to distinguish closely spaced cracks such as those caused by rolling contact fatigue (RCF). A multi-channel eddy current sensor array has been developed to detect defects on rails. Based on the sensor scanning data, defect reconstruction along the rails is achieved using an inverse algorithm that includes both direct and iterative approaches. In experimental evaluations, the EC system with the developed sensor is used to measure defects on a standard test piece of rail with a probe lift-off of 4-6 mm. The reconstruction results clearly reveal cracks at various depths and spacings on the test piece.

Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV PrEP have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6-months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. Conclusions: We conclude that in high antimicrobial consumption populations, the association between antimicrobial consumption and resistance may be attenuated.

Due to its similarity with human milk and its low allergenic properties, donkey milk has long been used as an alternative for infants and patients with cow's milk protein allergy. In addition, this milk is attracting growing interest in human nutrition because of presumed health benefits. It has antioxidant, antimicrobial, antitumoral, antiproliferative, and antidiabetic activity. Also, it stimulates the immune system, regulates the gastrointestinal flora, and prevents inflammatory diseases. Although all components of donkey milk can contribute to functional and nutritional effects, it is generally accepted that the whey protein fraction plays a major role. The purpose of this review is to highlight the active proteins and peptides of donkey milk in comparison with other types of milk, emphasizing their properties and their roles in different fields.

Keywords: pelvic ultrasound, follicle number per ovary, FNPO, ovarian volume, PCOM, upper normal limits, referral population

A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices which have been classified as “possibly carcinogenic”, however their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (RE) may promote genomic instability, here we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of RE, such as long interspersed nuclear element1s (LINE-1), Alu short interspersed nuclear element and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE1 and ribosomal repeats in terms of both average profiles and organization of methylated and un-methylated CpG sites, in different ways in each of the three cell lines studied.

Dental agenesis is one of the most common developmental anomaly in humans and it is frequently as-sociated with several other oral abnormalities. The present case describes nonfamilial agenesis of per-manent teeth in a twenty-one-year-old boy, with no apparent systemic abnormalities. The treatment in-cluded a personalized and interdisciplinary approach by the means of endodontics, orthodontics, im-plants supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing, and mock-up previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants, and monolithic Zirconia implant supported restorations. The final results showed a highly aesthetic and functional rehabilitation. Periodic checkups have shown that the stability of the result is well maintained and that the implant supported restorations are an op-timal solution for patients with multiple anodontia.

New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with emergence of resistance resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies, that are clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers and phages. Clinical diagnostics optimizes the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious disease include detection, monitoring of response and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives into the use of alternate therapeutics with a particular focus on companion diagnostic applications in infectious diseases.