RNAi technology is a versatile, effective, safe, and eco-friendly alternative for crop protection. There is plenty of evidence of its use through host-induced gene silencing (HIGS) and spray-induced gene silencing (SIGS) techniques to control viruses, bacteria, fungi, insects, and nematodes. For SIGS, its most significant challenge is achieving stability and avoiding premature degradation of RNAi in the environment or during its absorption by the target organism. One alternative is encapsulation in liposomes, virus-like particles, polyplex nanoparticles, and bioclay, which can be obtained through the recombinant production of RNAi in vectors, transgenesis, and micro/nanoencapsulation. The materials must be safe, biodegradable, and stable in multiple chemical environments, favoring the controlled release of RNAi. Most of the current research on encapsulated RNAi focuses primarily on oral delivery to control insects by silencing essential genes. The regulation of RNAi technology focuses on risk assessment using different approaches; however, this technology has positive economic, environmental, and human health implications for its use in agriculture. The emergence of alternatives combining RNAi gene silencing with the induction of resistance in crops by elicitation and metabolic control is expected, as well as multiple silencing and biotechnological optimization of its large-scale production.

If a lubricant contains structures capable of conducting energy, reactions involving zinc dialkyldithiophosphate (ZDDP) may take place both very close to and away from the solid surfaces, with this indicating that ZDDP can be a highly effective anti-wear (AW) additive. The central thesis of this article is that the tribocatalytic effect is observed only when the energy emitted by the solids is transmitted by ordered molecular structures present in the lubricant, e.g., graphene. The friction tests were carried out for 100Cr6 steel balls in a sliding contact with uncoated or a:C-H-coated HS6-5-2C steel discs in the presence of polyalphaolefin 8 (PAO 8) as the lubricant, which was enhanced with graphene and/or ZDDP. There is sufficient evidence of the interactions occurring between ZDDP and graphene and their effects on the tribological performance of the system. It was also found that the higher the concentration of zinc in the wear area, the lower the wear. This was probably due to the energy transfer resulting from the catalytic decomposition of ZDDP molecules. Graphene, playing the role of the catalyst, contributed to that energy transfer.

Temperature and pH can expedite the ability of pathogens to cause diseases in cold-water corals (CWCs). The present study employed a combination of histology and polymerase chain reaction diagnostic techniques to investigate potential pathogens present in the CWCs Lophelia pertusa and Madrepora oculata in the Porcupine Bank Canyon (PBC), NE Atlantic. No pathogen was observed in the Madrepora samples. Neither histology nor standard PCR detected Vibrio spp. in the corals, although using Illumina technology, V. shilonii was observed in some L. pertusa samples in low abundances (0.22%). A Rickettsiales-like organisms (RLOs) occurred at a prevalence of 8.0% and at a low infection intensity of 1 - 4. Lophelia showed a few RLOs infection from the PBC canyon head (2.7%) and high infections in the south branch (5.3%). Similarly, unidentified cells observed in L. pertusa from the south branch (4.0%) were more common than those found in the canyon head (1.3%) with a prevalence of 5.3%. Although the route of pathogen infection is unclear, a likely mode of entry could be associated with particulate availability and the feeding strategies of the scleractinian corals. This suggest that L. pertusa invests energy into an enhanced immune function and reduced susceptibility to global pathogens despite a changing ocean environment.

Angiotensin converting enzyme 2 (ACE2) is a key entry point of SARS-CoV-2 virus known to induce COVID-19. We have recently outlined the concept to reduce ACE2 expression by the administration of glycyrrhizin, a component of Glycyrrhiza glabra extract, via its inhibitory activity on 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2) and resulting activation of mineralocorticoid receptor (MR). We hypothesized that in organs, such as the intestine, which co-express 11betaHSD2, MR and ACE2, the expression of ACE2 would be suppressed. We studied organ tissues from an experiment originally designed to address the effects of Glycyrrhiza glabra extract on the stress response. Male Sprague Dawley rats were left undisturbed or exposed to chronic mild stress for five weeks. For the last two weeks, animals continued with a placebo diet or received a diet containing extract of Glycyrrhiza glabra root at a dose of 150 mg/kg of body weight/day. Quantitative PCR measurements showed a significant decrease in gene expression of ACE2 in the small intestine of rats fed with diet containing Glycyrrhiza glabra extract. This effect was independent of the stress condition and failed to be observed in non-target tissues, namely the heart and the brain cortex. In the small intestine we confirmed the reduction of ACE2 also at the protein level. Present findings provide first evidence to support the hypothesis that Glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2. Whether this phenomenon, when confirmed in additional studies, is linked to the susceptibility of cells to the virus requires further studies.

Staphylococcus aureus is a Gram-positive bacterium causing a range of mild to life-threatening infections including bone infections such as osteomyelitis. S. aureus is able to invade and persist within non-professional phagocytic cells such as osteoblasts. In the present study four different S. aureus strains, 2SA-ST239-III, 5SA-ST5-II, 10SA-ST228-I, and 14SA-ST22-IVh were tested for their ability to modulate cell viability in MG-63 osteoblast-like cells following a successful invasion and persistence. Methicillin-sensitive S. aureus (MSSA) ATCC-12598-ST30 was used as control. Despite the demonstrated similar abilities of internalization and persistence of ATCC-12598-ST30, 2SA-ST239-III, and 14SA-ST22-IVh strains in MG-63 osteoblast-like cells under our experimental conditions, we demonstrated that the decrease in cell viability was due to the different behavior of the considered strains, with the number of intracellular bacteria playing a limited role. We focused our attention on different cellular biochemical functions related to inflammation, cell metabolism, and oxidative stress during osteoblast infections. We were able to show that: 1) ATCC-12598-ST30 and 2SA-ST239-III were the only two clones able to persist and maintain their number into the cellular hostile environment during the entire period of infection; 2) 2SA-ST239-III was the only clone able to significantly increase the gene expression (3 and 24 h) and protein secretion (24 h) of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MG-63 osteoblast-like cells; 3) the same clone determined a significant up-regulation of transforming growth factor-β1 (TGF-β1) and the metabolic marker glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNAs at 24 h post infection; 3) neither the MSSA nor the four MRSA strains induced oxidative stress phenomena in MG-63 cells, although a very different expression pattern towards nuclear factor E2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) activation was observed among the different clones. Our results can open a new way of considering therapies, going in the direction of an individualized therapeutic strategy that should take into account the difference existing between MSSA and MRSA as well as the distinctive features of the different clones. Not only, therefore, a different antibiotic approach but also a starting point for considering different host factors, i.e. the modulation of specific cytokines such as IL-6, TNF-α, and TGF-β1.

The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection or inflammation of the ENS highlights its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI disorders such as short bowel syndrome with neuronal pathophysiology. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances, and ultimately change our approach to GI disorders.

The asymptotic dynamics of the classes of rational difference equations (RDEs) of third order defined over the positive real-line as $$\displaystyle{x_{n+1}=\frac{x_{n}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-1}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-2}}{ax_n+bx_{n-1}+cx_{n-2}}}$$ and $$\displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-1}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-2}}}$$ is investigated computationally with theoretical discussions and examples. It is noted that all the parameters $a, b, c$ and the initial values $x_{-2}, x_{-1}$ and $x_0$ are all positive real numbers such that the denominator is always positive. Several periodic solutions with high periods of the RDEs as well as their inter-intra dynamical behaviours are studied.

Cellular substructure has been widely observed in the sample fabricated by laser powder bed fusion, while its growth direction and the crystallographic orientation have seldom been studied. This research tries to build a general model to construct the substructure from its two-dimensional morphology. All the three Bunge Euler angles to specify a unique growth direction are determined, and the crystallographic orientation corresponding to the growth direction is also obtained. Based on the crystallographic orientation, the substructure in the single track of austenitic stainless steel 316L is distinguished between the cell-like dendrite and the cell. It is found that, with the increase of scanning velocity, the substructure transits from cell-like dendrite to cell. When the power is 200 W, the critical growth rate of the transition in the single track can be around 0.31 ms^-1.

The growing demand for phycobiliproteins from microalgae generates a significant volume of by-products, such as extraction cakes. These cakes are enriched with products of interest for the cosmetic market, namely free fatty acids, particularly polyunsaturated (PUFA). In this work, two cakes, one of spirulina and one of Porphyridium cruentum, were valorized using innovative natural hydrophobic deep eutectic solvents (NaDES) based on alkanediols. The most promising NaDES, as determined by physicochemical properties and screening, are mixtures of alkanediol and fatty acid. These include the mixture of 1,3-propanediol and octanoic acid (1:5, mol/mol) and 1,3-propanediol and octanoic and decanoic acid (1:3:1, mol/mol). Two extractive processes were implemented: ul-trasound-assisted extraction and an innovative mechanical process by dual asymmetric centrifu-gation. The second process resulted in the production of extracts significantly enriched in PUFA, ranging from 65 to 220 mg/g dry matter with the two cakes. The extracts and NaDES demonstrated good safety with respect to epidermal keratinocyte viability. The study of their impact on com-mensal and pathogenic cutaneous bacteria demonstrated significant effects on viability of Staphy-lococcus aureus and Staphylococcus epidermidis while preserving Corynebacterium xerosis and Cuti-bacterium acnes. These results highlight the potential of valorizing these co-products using al-kanediol-based NaDES, in a strategy combining an active vector (NaDES) and a growth regulator extract, for the management of cutaneous dysbiosis involving staphylococci.

The in vitro cultivation of M. leprae has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria-human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of M. leprae as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium until 60 days. Explants were evaluated by RT-PCR-16SrRNA, and cytokines gene expression. Viability and infectivity of bacilli recovered from explant (D28 and D60) were evaluated using the Shepard’s model. All explants were RT-PCR-16srRNA positive. Viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice showed an average positivity of 31%, being the highest positivity in the D28 groups (80%). Furthermore, our work showed different pattern in cytokines gene expression (TGF-β, IL-10, IL-8 and TNF-α) in the presence of alive or dead bacilli. Although changes can be made for improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain M. leprae for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing some antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrating remarkable efficacy against planktonic cells and biofilms of MRSA, outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, was showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wound in mice. Together the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

In the last ten years, plasma waste treatment has gained increasing prominence as a technology in response to growing challenges in waste disposal and the recognition of opportunities for generating valuable by-products. The efficiency and outcomes of this process are intricately linked to the characteristics of the plasma involved, such as plasma enthalpy and heat flux. We employed an experimental radio frequency inductively coupled plasma (RF-ICP) torch operating at atmospheric pressure to generate plasma. Utilizing optical emission spectroscopy (OES), we measured plasma parameters, specifically the effective electron temperature (Teff) and plasma density (ne), while varying argon gas flow rates and RF powers. Our investigations revealed that both flow rate and RF power exert significant control over plasma parameters, and we observed an unusual phenomenon within this range of discharge pressures. Consequently, both the plasma's enthalpy and the heat flux it generates are influenced by variations in both flow rate and RF power.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents. Ethyl acetate fraction(EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-, and di-glycoside of each aglycone. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Leukemia cutis (LC) is defined as leukemic infiltration of the epidermis, the dermis, and the subcutaneous tissue. Leukemia cutis may follow or occur simultaneously with the diagnosis of systemic leukemia. However, cutaneous lesions are occasionally diagnosed as the primary manifestation of leukemia. Leukemic skin infiltrations demonstrate considerable variation regarding number of changes, distribution, and morphology. The highest incidence of LC is observed in chronic lymphocytic leukemia, monocytic and myelomonocytic acute myeloid leukemia, and in T-cell lineage leukemia. Although the pathogenic mechanism of the invasion of leukemic cells into the skin is not well understood, chemokine receptors and adhesion molecules as well as genetic characteristics of leukemia are thought to play a role. Leukemic skin lesions may be localized or disseminated and may occur alone or in combination on any site of the skin, most frequently in the trunk and extremities. The most common clinical presentations of leukemia cutis are papules, nodules, macules, plaques, and ulcers. In most patients, complete or partial resolution of cutaneous infiltrations occurs simultaneously with hematologic remission. However, in patients with resistant disease or recurrent skin infiltration, local radiotherapy can be used. This review presents recent data on the pathogenesis, diagnosis and treatment of leukemic skin involvement in different types of leukemia

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the ex-pression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug, 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of ectoine in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA methyla-tion-related gene and marker analysis were performed. The results showed that ectoine hypo-methylation in skin cells, especially in the CpG island (CGIs) element and 5mC, was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation, but did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3i, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Igf2, Snrpn, and Mest. Overall, ectoine, an excellent DNA protectant, mildly de-methylates DNA in skin cells, modulates the expression of methylation-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.

This study aims to investigate the impact of body heat loss on the thermal and aerodynamic conditions in a whole-body cryotherapy chamber. The underlying hypothesis is that the heat generated by the human body alters the thermal and aerodynamic environment inside the cabin. A numerical study was conducted to test this hypothesis to analyze the thermodynamic exchanges between the human body and the cabin during a 3-minute whole-body cryotherapy session. The computational fluid dynamics (CFD) approach was used to study the unsteady heat transfer between the human body and the interior of the cryotherapy cabin. A thermal boundary condition, based on a mathematical model developed from experimental data, was applied to simulate skin cooling kinetics over time. The post-processing of the 3D results, including temperature, velocity fields, and thermal flux maps at the body surface, provided insight into the thermo-convective mechanisms involved in a whole-body cryotherapy session. The study found that body heat loss significantly affects the temperature fields inside the cabin, leading to global modifications of the aeraulic and thermal conditions. These findings suggest that cryotherapy protocols may need to be adjusted or the cabin set temperature optimized to enhance the therapeutic benefits.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

Brachycephalic dogs are not only affected by brachycephalic obstructive airway syndrome (BOAS), but also comprise up to 30% of canine patients seen by veterinary dermatologists, with English Bulldogs and Pugs particularly overrepresented. Some skin diseases are associated with the abnormal anatomic conformation of brachycephalic dogs, while for others there is a underlying genetic basis or a general predisposition. Anatomic alterations associated with brachycephaly, leading to fold formation of the skin and stenosis of the ear canal, together with primary immunodeficiencies described in some breeds, favor the development of pyoderma, Malassezia dermatitis and otitis externa/media. Frequently neglected but often lifelong dermatological problems of brachycephalic dogs are an important consideration when discussing genetic and medical conditions affecting the welfare of those dogs. Here we review the current state of knowledge concerning dermatological problems of brachycephalic dogs, and combine it with clinical experience in the management of these challenging disorders.

Infectious diabetic wounds can result in severe injuries or even death. Biocompatible wound dressings offer one of the best ways to treat these wounds, but creating a dressing with suitable hydrophilicity and biodegradation rate can be challenging. To address this issue, we used the electrospinning method to create a wound dressing composed of poly(glycerol sebacate) (PGS) and gelatin (Gel). We dissolved the PGS and Gel in acetic acid (75 v/v%) and added EDC/NHS solution as a crosslinking agent. Our measurements revealed that the scaffolds' fiber diameter ranged from 180.2 to 370.6 nm, and all the scaffolds had porosity percentages above 70%, making them suitable for wound healing applications. Additionally, we observed a significant decrease (p < 0.05) in the contact angle from 110.8° ± 4.3° for PGS to 54.9° ± 2.1° for PGS/Gel scaffolds, indicating an improvement in hydrophilicity of the blend scaffold. Furthermore, our cell viability evaluations demonstrated a significant increase (p < 0.05) in cultured cell growth and proliferation on the scaffolds during the culture time. Our findings suggest that the PGS/Gel scaffold has potential for wound healing applications.

In diabetic foot infections (DFI), the clinically virulence of skin commensals are generally pre-sumed to be of low virulence. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria); and, pyogenicpathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1,018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pyogenicpathogenic patho-gens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxy-gen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs 24 %, p=0.23) or microbiological recurrence (11% vs 17 %, p=0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confi-dence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may equally base on oral non-beta-lactam antibiotic agents susceptible to the corresponding skin pathogens.

Melanoma is considered to be the most aggressive form of skin cancer. Due to the similar shape of malignant and benign cancerous lesions, doctors spend considerably more time when diagnosing these findings. At present, the evaluation of malignancy is performed primarily by invasive histological examination of the suspicious lesion. Developing an accurate classifier for early and efficient detection can minimize and monitor the harmful effects of skin cancer and increase patient survival rates. This paper proposes a multi-class classification task using the CoAtNet architecture, a hybrid model that combines the depthwise convolution matrix operation of traditional convolutional neural networks with the strengths of Transformer models and self-attention mechanics to achieve better generalization and capacity. The proposed multi-class classifier achieves an overall precision of 0.901, recall 0.895, and AP 0.923, indicating high performance compared to other state-of-the-art networks.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy Body Dementia (LBD), which includes Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer pathology as well as novel biomarkers were discussed.

The pomegranate, an ancient plant native to Central Asia, cultivated in different geographical areas including the Mediterranean basin and California, consists of flowers, roots, fruits and leaves. Presently, it is utilized not only for the exterior appearance of its fruit but above all, for the nutritional and health characteristics of the various parts composing this last one (carpellary membranes, arils, seeds and bark). The fruit, the pomegranate, is rich in numerous chemical compounds (flavonoids, ellagitannins, proanthocyanidins, mineral salts, vitamins, lipids, organic acids) of high biological and nutraceutical value that make it the object of study for many research groups, particularly in the pharmaceutical sector. Its interest is mainly addressed to the knowledge of its biological and functional properties and the research of new formulations to apply it in a wide range of diseases such as neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases. In this review we highlight the health-promoting properties of pomegranate and its bioactive compounds against human diseases.

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

The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-like family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which reveal significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~ 90 potential genes that participate in the regulation of the hypertrophic environment (or CVD's Environment). Also, the GO analysis showed genes containing the motif CACCC were enriched for multiple CVD’s, in combination with STRING analysis these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

Chlamydia trachomatis (Ct) infections are the most common sexually-transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we use the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial protease-like activity factor (CPAF) protein. We tested two weekly administration options – twice intranasal (IN) followed by twice intramuscular (IM), or twice IM followed by twice IN. We assessed the humoral immune response not only in serum by CPAF-specific IgG including antibody avidity determination but also in cervical and rectal swabs by CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed upon in vitro CPAF-restimulation via IFN-γ and IL-17 ELISpots as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response: Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response by CD4 T cells. In the IM/IN vaccinated pigs, these cells also significantly downregulated their CCR7 expression – a sign for differentiation into peripheral tissue homing effector/ memory cells. Conclusively, this study demonstrates strong immunogenicity of the IM/IN administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

Recent studies have elucidated the diversity of genes encoding venom in sea anemones. However, most of those genes are yet to be explored in an evolutionary context. Insulin is a common peptide across metazoans and has been coopted into a predatory venom in many venomous lineages. In this study, we focus on the diversity of insulin-derived venoms in sea anemones and on elucidating their evolutionary history. We sourced data for 34 species of sea anemones and found sequences belonging to two venom families that have Insulin PFAM annotations (Cono-Insulin, VP302). Our findings show that both families have undergone duplication events. Members of each of the independently evolving clades have consistent predicted protein structures and distinct dN/dS values. Our work also shows that VP302 is part of a multidomain venom contig and has experienced a secondary gain into the venom system of cuticulate sea anemones.

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the Lower Middle São Francisco region. Methods: This is an analytical cohort, with a quantitative approach and a translational perspective. Thirty children with low and normal birth weight were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves at birth, third month, and sixth month of life. Results: Weight gain during the 6 months of follow-up in newborns with low birth weight was greater compared to newborns with normal birth weight. All children who were born with low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with low birth weight. Conclusion: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with low birth weight, with greater adiposity in this group, which may increase the risk of metabolic diseases in later life.

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as a promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become a focal point in contemporary research. The adenosine triphosphate (ATP)-binding site and the polo-box domain in PLK1 present crucial interaction sites for these inhibitors, aiming to disrupt the protein's function. However, designing potent and selective small-molecule inhibitors can be challenging, requiring a deep understanding of protein-ligand interaction mechanisms at these binding sites. In this context, our study leverages the fragment molecular orbital (FMO) method to explore these site-specific interactions in-depth. Through the FMO approach, we used the FMO method to elucidate the molecular mechanisms of small-molecule drug binding to these sites to design PLK1 inhibitors that are both potent and selective. Our investigation further entailed a comparative analysis of various PLK1 inhibitors, each characterized by distinct structural attributes. This comparison enhanced our understanding of the structure-activity relationships of these inhibitors, underscoring the efficacy of the FMO method in identifying critical binding features and predicting binding modes for small-molecule ligands. Furthermore, Our research spotlighted "hot spot" residues instrumental for selective and robust PLK1 binding. Our findings offer profound insights, priming the rational design of innovative potential PLK1 inhibitors with significant implications for developing anticancer therapeutics.

With the increment of the aging population in recent years, neurodegenerative diseases exert a major global disease burden, essentially as a result of the lack of treatments that can stop the disease progression. Alzheimer’s Disease (AD) is an example of a neurodegenerative disease, that affects millions of people globally, with no effective treatment. Natural compounds have emerged as a viable therapy to fill a huge gap in AD management, and in recent years, mostly fuelled by the Covid-19 pandemic, RNA-based therapeutics have become a hot topic in the treatment of several diseases. Treatments of neurodegenerative diseases face significant limitations due to the complex and interconnected pathways that lead to their hallmarks and, also due to the necessity to cross the blood–brain barrier. Nanotechnology has contributed to surpass this bottleneck in the treatment of AD, by promoting safe and enhanced drug delivery to the brain. In particular, exosome-like nanoparticles, a hybrid delivery system combining exosomes and liposomes' advantageous features, are demonstrating great potential in the treatment of central nervous system diseases.

In this work, we present a new way to study the genetic code mathematical and chemical structure, based on the use of mathematical computations involving some few recently designed Fibonacci-like sequences, the “seeds” (“initial conditions”) of which are chosen according to the chemical and physical data of the three amino acids serine, arginine and leucine, playing a prominent role in a recent symmetry classification scheme of the genetic code. It appears that these mathematical sequences, of the same kind as the famous Fibonacci series, apart from their usual recurrence relations, are highly interwinned by many useful linear relationships. Using these sequences and also various sums or linear combinations of them, we derive several physical and chemical quantities of interest, as the number of total coding codons, 61, obeying various degeneracy patterns, the detailed number of hydrogen atoms, the detailed number of atoms (H/CNOS) and the integer molecular mass (or nucleon number), in the side chains of the 61 “amino acids”, also in various degeneracy patterns, in agreement with those described in the literature. Also, unexpectedly but interestingly, we find, as a by-product, an accurate description of the very chemical structure of the four ribonucleotides uridine monophosphate (UMP), cytidine monophosphate (CMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP), the building blocks of RNA whose groupings, in three units, constitutes the triplet codons. In summary, we find a full mathematical and chemical connection with the “ideal sextet’s classification scheme” mentioned above as well as with several others, notably, the Findley-Findley-McGlynn symmetrical classification. We organize the content of the text in such a way that, besides the presentation of several new research results, it has also an educational dimension. The paper could therefore be read and the computations easily worked out, also by non-experts with mathematical background.

The increasing prevalence of depression worldwide requires more effectiveness in therapy approaches and a molecular understanding of antidepressants mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography-high resolution mass spectrometry. The behavioral phenotype was assessed by the forced swim test. To analyze metabolomics data, univariate and multivariate analysis and biomarker capacity assessment using the classical receiver operating characteristic (ROC) curve were used. Support vector machine-linear kernel (SVM-LK), as a machine-learning algorithm was performed for binary classification. Upregulated myo-inositol following CSIS may represent a potential marker of depressive phenotype. Effective fluoxetine treatment reversed depressive-like behavior and increased sedoheptulose 7-phosphate, hypotaurine, and acetyl-L-carnitine contents, which were identified as potential markers. We identified 4 or 10 marker candidates with ROC curve greater than 0.9 for CSIS or fluoxetine effectiveness designation. SVM-LK has given accuracy of 61.50%, or 93.30%, and 7 or 25 predictive metabolites for CSIS vs. control and fluoxetine-treated CSIS vs. CSIS classification. Overall, metabolic fingerprints combined with ROC curve and SVM-LK may represent a new approach to identifying potential markers or predicting metabolites for group designation or classification.

In general, isolators and dampers used in seismically isolated buildings are designed to be isotropic in any horizontal direction. However, in the case of buildings with plan irregularities, their nonlinear responses depend on the direction of seismic loading. To discuss the influence of the angle of seismic incidence (ASI) on the nonlinear response of irregular building structures, it is important to define the angle of the critical axis of the horizontal ground motion. One possible choice is the “principal axis of ground motion” proposed by Arias (1970). However, because this principal axis is independent of the natural period of a structure, it could be complicated to use for seismically isolated structures with long natural periods. In this study, the influence of the ASI of long-period pulse-like seismic input on an irregular base-isolated building is investigated. First, the angle of the principal axis of ground motion is defined in terms of the cumulative energy input. Then, a nonlinear time-history analysis of a five-story irregular base-isolated building is performed using 10 long-period pulse-like ground motion records considering various ASIs. The results show that, compared with the principal axis of ground motion proposed by Arias, defining the principal axis of ground motion in terms of the cumulative energy input is more suitable for discussions concerning the influence of the ASI on the response of an irregular base-isolated building.

The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, TALE and CRISPR-Cas9 revealed common rules, which can help the optimization of activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression, and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor systematically optimized designer transcription factors to the needs of specific applications.

In this paper, we study the weak gravitational deflection angle of relativistic massive particles by the Kerr-like black hole in the bumblebee gravity model. In particular, we focus on weak field limits and calculate the deflection angle for a receiver and source at a finite distance from the lens. To this end, we use the Gauss-Bonnet theorem of a two-dimensional surface defined by a generalized Jacobi metric. The spacetime is asymptotically non-flat due to the existence of a bumblebee vector field. Thus the deflection angle is modified and can be divided into three parts: the surface integral of the Gaussian curvature, the path integral of a geodesic curvature of the particle ray and the change in the coordinate angle. In addition, we also obtain the same results by defining the deflection angle. The effects of the Lorentz breaking constant on the gravitational lensing are analyzed. We then consider the finite-distance correction for the deflection angle of massive particles.

Ebola Virus Disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and caused by members of the Filoviridae family. The recent large outbreak of EVD in West Africa (2013-2016), highlighted the worldwide danger of this disease and its impact on global public health and economy. The development of highly needed anti-Filoviridae antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, and therefore screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to in vitro study of Filoviridae entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus like particles, tremendously boosted both our knowledge on viral life cycle and the identification of promising anti-Filoviridae compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.

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

In recent years, there has been a growing interest in the use of medicinal plants and phytochemicals as potential treatments for acne vulgaris. This condition, characterized by chronic inflammation, predominantly affects adolescents and young adults. Conventional treatment typically targets the key factors contributing to its development: the proliferation of Cutibacterium acnes and the associated inflammation. However, these treatments often involve the use of potent drugs. As a result, the exploration of herbal medicine as a complementary approach has emerged as a promising strategy. By harnessing the therapeutic properties of medicinal plants and phytochemicals, it may be possible to address acne vulgaris while minimizing the reliance on strong drugs. This approach not only offers potential benefits for individuals seeking alternative treatments but also underscores the importance of natural remedies in dermatological care. The primary aim of this study was to assess the antimicrobial, antioxidant, and anti-inflammatory properties of plants and their phytochemical constituents in the management of mild acne vulgaris. A comprehensive search of scientific databases was conducted from 2018 to September 2023. The findings of this review suggest that medicinal plants and their phytochemical components hold promise as treatments for mild acne vulgaris. However, it is crucial to note that further research employing high-quality evidence and standardized methodologies is essential to substantiate their efficacy and safety profiles.

The presence of valuable bioactive compounds in European eel (Anguilla anguilla) skin was studied. For it, proximate and lipid class compositions and analysis of the fatty acid (FA) profile (individual FAs; FA groups, i.e., saturated, monounsaturated, and polyunsaturated; FA ratios, i.e., polyunsaturated/saturated, ω3/ω6) were determined and compared to the composition of the eel muscle. As a result, higher (p<0.05) levels of proteins (271.6 g·kg-1), lipids (38.0 g·kg-1), ash (27.7 g·kg-1) and ω6 FAs were observed in the skin tissue. Contrary, the muscle tissue showed higher (p<0.05) moisture, ω3 FA and ω3/ω6 values. Regarding lipid classes, a higher (p<0.05) proportion of phospholipids (111.1 g·kg-1 lipids), sterols (104.7 g·kg-1 lipids), α-tocopherol (274.0 mg·kg-1 lipids), and free fatty acids (43.6 g·kg-1 lipids) was observed in the skin tissue. No differences (p>0.05) between both tissues could be detected for triacylglycerol and FA group (saturated, monounsaturated, and polyunsaturated) values, as well as for the polyunsaturated/saturated ratio. It is concluded that eel skin, a by-product resulting from commercial processing, can be considered a valuable source to provide the food and pharmaceutical industries with useful value-added constituents such as proteins, lipids, ω3 FAs, phospholipids, and α-tocopherol.

Aging, a natural process occurring in both normal and degenerative conditions, is closely associated with collagen degradation, impacting various bodily systems such as the skin. The continuous aging of the skin, influenced by both intrinsic and extrinsic factors, underscores the importance of collagen in dermatological and cosmetic contexts. Notably, collagen supplements enriched with essential amino acids like proline and glycine along with marine fish collagen have become popular for their safety and effectiveness in mitigating the aging process. To compile relevant literature on the anti-aging applications of marine collagen, a systematic search and analysis of peer-reviewed papers was conducted using reputable databases including PubMed, Cochrane Library, Web of Science, and Embase, covering publications from 1956 to 2023. From in vitro to in vivo experiments, the reviewed studies elucidate the anti-aging benefits of marine collagen, emphasizing its role in combating skin aging and promoting overall skin health. Many bioactive marine peptides exhibit diverse anti-aging properties, including free radical scavenging, apoptosis inhibition, lifespan extension in various organisms, and protective effects in aging humans. Furthermore, the peptide production of hyaluronic acid is discussed as a mechanism to fortify collagen and enhance skin moisture, contributing to the anti-aging effects of collagen supplementation. The integration of bio-tissue engineering in marine collagen applications is also explored, highlighting its proven utility in addressing skin and bone damage. Insights from this review illuminate the diverse biomedical applications of marine collagen alongside keystone molecular editing tools such as CRISPR, positioning it as a versatile resource in anti-aging interventions. However, limitations to the scope of its application exist. Thus, by delving into these nuanced considerations, this review contributes to a comprehensive understanding of the potential and challenges associated with marine collagen in the realm of anti-aging applications.

Transdermal drug delivery systems (TDDS) are designed to administer a consistent and effective dose of medication through the patient's skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. This medication provides a continuous and prolonged administration of a substance at a consistent rate. TDDS, or transdermal drug delivery system, has gained significant attention as a non-invasive method of administering drugs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first-pass metabolism and the corrosive acidic environment of the stomach that happens when medications are taken orally. Multiple methodologies have been devised to augment the transdermal permeability of diverse pharmaceutical substances. Recent advancements in transdermal drug delivery systems have facilitated the precise delivery of medications to the intended site of action by improving the penetration of drugs through the outermost layer of the skin, known as the stratum corneum, resulting in enhanced drug availability throughout the body. This review seeks to provide a concise overview of the several methods employed in the production of TDDS, as well as their evaluation, therapeutic uses, clinical considerations, and current advancements. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient transdermal drug delivery systems.

AK is a common precancerous skin condition that requires effective detection and treatment monitoring. To improve the monitoring of AK burden in clinical settings with enhanced automation and precision, the present study evaluates the application of semantic segmentation based on the U-Net architecture (AKU-Net). AKU-Net employs transfer learning to compensate for the relatively small dataset of annotated images and integrates a recurrent process based on convLSTM to exploit contextual information and address the challenges related to low contrast and ambiguous boundaries of AK-affected skin regions. We used an annotated dataset of 569 clinical photographs from 115 patients with actinic keratosis to train and evaluate the model. From each photograph, patches of 512x512 pixels were extracted using translation lesion boxes that encompass lesions in different positions and capture different contexts of perilesional skin. In total, 16488 translation augmented crops were used for training the model, and 403 lesion center crops were used for testing. To demonstrate the improvements in AK detection, AKU-net was compared with plain U-Net and U-Net++ architectures. The experimental results highlighted the effectiveness of AKU-Net, improving both automation and precision over existing approaches, paving the way for more effective and reliable evaluation of actinic keratosis in clinical settings.

(1) Background: This case report focuses on a 46-year-old female patient diagnosed with a rare and aggressive form of breast cancer known as rapidly growing, ulcerated breast cancer. The patient exhibited rapid progression of the disease, experiencing discomfort and noticeable changes in the size and texture of the affected breast over a short period of time; (2) Methods: An intensive neoadjuvant chemotherapy regimen was employed as the primary treatment approach. The patient's response to this treatment was closely monitored and assessed. Various diagnostic tests and imaging techniques were utilized to evaluate the extent of the disease and track its response to the chemotherapy; (3) Results: The patient's response to the neoadjuvant chemotherapy regimen was remarkable, resulting in a complete pathologic response. This outcome, although unusual in rapidly growing, ulcerated breast cancers, highlights the effectiveness of neoadjuvant chemotherapy in managing large, locally advanced breast cancers; (4) Conclusions: The multidisciplinary approach employed in managing this complex breast cancer case proved to be crucial to the patient's favorable outcome. Despite the aggressive nature of the disease and the challenges posed by the rapid growth and ulceration, the patient achieved a positive result. This case contributes to the limited clinical literature on such unusual and aggressive breast cancer cases, providing valuable insights for future clinical practice.8

Abstract: Pasteurella spp. is a gram-negative bacterium that is part of the oral and upper respira-tory tract microbiota of many animals such as canids and felines. In humans it can produce pa-thology primarily associated with animal bites or scratches. In addition, members of this genus, and especially Pasteurella multocida, may also be involved in systemic infections, mainly in im-munocompromised patients in close contact with pets. The aim of this study is to analyse the prevalence and clinical characteristics of infections caused by Pasteurella spp. as well as the sensitivity profile of these isolates obtained in the Microbiology laboratory of the Hospital Can Misses (Ibiza, Ibiza and Formentera Health Area, ASEF) in the period from January 2013 to December 2018. The group of islands of Ibiza and Formentera is known as the Pitiusas Islands. Retrospective descriptive study in which all Pasteurella spp. isolates were analysed in the Microbiology Laboratory of Hospital Can Misses from 1 January 2013 to 31 De-cember 2018. Bacterial identification was performed by Vitek 2 automated biochemical test panel (bioMérieux, Spain) and antimicrobial susceptibility by E-test or antibiotic discs in Mueller-Hinton blood agar, interpreted based on European Committee on An-timicrobial Susceptibility Testing (EUCAST) standards, 2022 version. Medical records were systematically reviewed by collecting demographic data of infected patients, comorbidities, epidemiological data and clinical features of the infection. A total of 22 isolates of Pasterurella spp. were obtained from 22 different patients, 62.8% female, from three different species: 18 P. multocida, 2 P. canis and 2 P. pneumo-tropica. Most isolates came from soft tissue infection samples: 7 wound exudates and 5 abscess material. The antibiotics tested with the highest sensitivity profile were gen-tamicin and cefepime (100% sensitivity). The species most commonly isolated in our environment is P. multocida. Close contact with companion animals, especially cats and dogs, is the main risk factor for Pasteurella spp. infections, although in many cases such contact cannot be established. So Pasteurella spp. infection should be considered a zoonosis in possible emergency, especially in rural areas such as Pitiusas Islands.

According to the eminent scholar, philosopher, and physician Avicenna, "the doctor has three tools: the word, the plant, the knife." The plant kingdom is recognized as humanity's earliest and most ancient healing source, employed for the management and prevention of illnesses. Tracing back through history, the most ancient documented proof of plants' utilization in medicine dates back to a Sumerian clay slab discovered in Nagpur roughly 5000 years ago. This artifact included a compilation of twelve medicinal recipes that involved over 250 diverse plant species. Sumerian healers extracted powders and infusions from plant roots and stems, while also crediting healing properties to pears and figs. Additionally, they utilized dried and ground young shoots of willow and plum trees, pine and fir needles as a component in compresses and poultices. Often, powders from animal and mineral sources were blended with those extracted from dried and crushed plants. Notably, in addition to water, wine and beer served as solvents. Thus, at least 80 centuries ago, people utilized the most uncomplicated medicinal plant-based preparations for treatment [1]. The "Pen T'Sao," an ancient Chinese text on roots and herbs, authored by Emperor Shen Nung approximately 2500 BC, contains descriptions of 900 medicaments (comprising dried components of medicinal plants). Several of these substances are still in use today, including Rhei rhisoma, camphor, Theae folium, Podophyllum, great yellow gentian, ginseng, datura, cinnamon bark, and ephedra [2]. Regarding Kazakh folk medicine, an area that has yet to be fully explicated and substantiated, it can be stated that the traditional medicinal knowledge of the Kazakh people transcends the mere treatment of ailments and rests on robust theoretical underpinnings. Oteiboydak Tleukabyluly (1388-1478), an astute healer and prominent figure in Kazakh folk medicine during the 15th century, comprehensively explicated the secrets of the healing art in his medical and ethnographic work "Medical Narrative," which he composed between 1466 and 1473 at the behest of az-Zhanibek Khan, who held him in high esteem as a great healer. This medical encyclopedia delineates the functions of various organs of the human body and provides a catalogue of the primary diseases associated with them. Furthermore, it includes a meticulous description of the methods used in traditional medicine at present, such as setting bones, listening to the pulse, and incantations. Through practical experimentation and experimentation conducted in the steppe laboratory, the healer formulated a total of 1,108 different medicinal compounds, of which 858 were derived from medicinal plants, 318 were extracted from animal organs, and roughly 60 were sourced from metals. The moniker "Teacher without a teacher" was bestowed on Oteiboydak Tleukabylov, who discovered methods for treating 1,050 different diseases [3]. At present, the employment of phytotherapy has gained widespread acceptance on a global scale. According to the World Health Organization's (WHO) global review of national policies concerning traditional, complementary, and alternative medicine, as well as the regulation of herbal medicines, there is an evident growth in the European and Asian market for herbal medicines [4]. Kazakhstan boasts a natural flora of over 6,000 plant species [5]. The exact number of medicinal plant species present in Kazakhstan remains uncertain, as the list continues to expand annually. More than 150 plant species have been employed in both official and folk medicine for various ailments. This review focuses on a selection of medicinal plants growing within the territory of the Republic of Kazakhstan that have traditionally been used to alleviate skin diseases. In conducting this study (2010-2023), emphasis was placed on the plants' phytochemical composition, with a particular focus on the principal components responsible for their therapeutic effects against inflammatory skin conditions such as dermatitis, atopic dermatitis, and eczema.

Electromagnetic eddy current sensors are commonly used to identify and quantify the surface notches of metals. However, the unintentional tilt of eddy current sensors affects results of size profiling, particularly for the depth profiling. In this paper, based on the eddy current thin-skin regime, a revised algorithm has been proposed for the analytical voltage or impedance of a tilted driver–pickup eddy current sensor scanning across a long ideal notch. Considering the resolution of the measurement, the bespoke driver–pickup, also termed as transmitter-receiver (T-R) sensor is designed with a small mean radius of 1 mm. Besides, the T-R sensor is connected to the electromagnetic instrument and controlled by a scanning stage with high spatial travel resolution , with a limit of 0.2 μm and selected as 0.25 mm. Experiments have been out on the voltage imaging of an aluminium sheet with 7 machined long notches of different depths using T-R sensor under different tilt angles. By fitting the measured voltage (both real and imaginary part) with proposed analytical algorithms, the depth profiling of notches is less affected by the tilt angle of sensors. From the results, the depth of notches can be retrieved within a deviation of 10 % for tilt angles up to 60 degrees.

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

Skin involvement is an overlooked aspect in the management of paediatric patients with type 1 diabetes. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: “children”, “pediatric/paediatric patients”, “skin”, “skin disorders”, “type 1 diabetes”. Dermatological side effects are frequently observed among diabetic children and adolescents. Insulin-induced lipodystrophies and allergic contact dermatitis caused by insulin pumps or glycaemic sensors are the most common skin reactions in these patients. Furthermore, several diabetes-associated skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum may already be present in paediatric age. Paediatric diabetes specialists should pay attention to their patients’ skin so as to recognize these disorders, identify the potential causes, and choose the most suitable treatment. Finally, the evaluation of skin concentrations of advanced glycation end-products using non-invasive diagnostic techniques may be used to assess the risk of chronic complications of diabetes as early as adolescence.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulate NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased secretion of various cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

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

СrAss-like phages play an important role in maintaining ecological balance in the human intestine microbiome. However, their lifestyle and genetic diversity are still insufficiently studied. In this study, a novel CrAssE-Sib phage genome belonging to the epsilon сrAss-like phage genomes was found. Detailed analysis indicated that CrAssE-Sib encodes unusual proteins – DNA primase, virion RNA polymerase, prophage antirepressor, and transcriptional repressor, as well as reverse transcriptase (RT) and receptor binding protein (RBP) that are part of diversity-generating retroelement (DGR). Comparative analysis showed that all epsilon сrAss-like phages are divided into two putative genera, which were proposed to name Epsilonunovirus and Epsilonduovirus; CrAssE-Sib belongs to the first of them. RT from CrAssE-Sib and several Epsilonunoviruses contains a specific motif in its fourth domain that was not previously found in RTs from phage and bacterial DGRs. In addition, RBP from CrAssE-Sib and all Epsilonunoviruses has a unique structure. The presence of the conservative prophage repressor and anti–repressors that belong to the lysogenic-to-lytic cycle switches indicate that CrAssE-Sib and other Epsilonunoviruses could be temperate. Epsilon сrAss-like phage substantially differ from other crAss-like phages, including zeta сrAss-like phages. This fact indicates the need to isolate these phages into a separate family.

Diamond-like carbon (DLC) films have a promising tribological application in green precision manufacturing, but their toughness represents a serious issue in the way of their application perspective. The film thickness is on the micrometer scale and makes conventional methods unsuitable for its toughness characterization. The absence of an accepted method for characterizing the DLC toughness has hindered the related research on the development of toughening methods and understanding the mechanism. This work intends to explore a relatively simple and acceptable characterization method to measure the film toughness. Moreover, toughening mechanisms of DLC films are proposed during the characterization to reveal the toughening mechanism. The toughness can be fully characterized through combining impact toughness and scratch toughness. The impact toughness can be obtained by observing the size of the indentation and the crack state around the indentation in the impact experiment. The scratch toughness could be assessed by combining the scratch morphology and Crack Propagation Resistance (CPRS). The improvement of film toughness should be carried out from two aspects: preventing microcrack initiation and suppressing crack propagation. Appropriate doping of non-carbide metal particles can effectively improve the toughness of the film, and there are seven main factors affecting the toughening of the film. Five toughening mechanisms of non-carbide metals from film preparation to test stage are revealed during the investigation of the change patterns.

The Chen circuit system, a three-dimensional autonomous system with intriguing dynamics, has gained considerable attention due to its potential applications in diverse scientific fields. In this article, a Chen circuit-like system is defined and a comprehensive dynamics has been studied. The system exhibits chaotic dynamics, limit cycles, and bifurcations, making it a captivating subject of study. By employing numerical simulations and analytical techniques, we explore the system's stability and identify critical parameter values leading to qualitative changes. Notably, we delve Hopf bifurcations, which give rise to stability changes and the emergence of limit cycles. Furthermore, we analyze the fractal dimension of the system's attractor, providing insights into its complexity and self-similarity. Through a systematic examination of the Chen circuit-like system, we deepen our understanding of its intricate dynamics and offer valuable insights into the underlying mechanisms. The findings contribute to the field of dynamical systems and hold potential implications in areas such as chaos-based secure communications, signal processing, and nonlinear control. This work serves as a valuable reference for researchers and practitioners interested in the dynamics and bifurcation analysis of nonlinear systems.

Cu-Sn shape-memory microwires were fabricated by a glass-coated melt spinning method. Effects of Sn content on the microstructure and mechanical property of microwires were investigated. The phase transforms from martensite to austenite with Sn content increasing from 14.0 atomic percent (at.%) to 16.5 at.%, and highly ordered intermetallic phase, δ, formed with higher Sn content. The fracture stress, σf, and the critical stress for martensitic transformation, σMs, increases with Sn content increasing. The mechanical property as well as superelasticity were improved greatly by high cooling rate of the glass-coated melt spinning method.

The response of structures under pulse-like ground motions is characterized by the large amount of energy input in a few cycles. Consequently, structures with insufficient strength may suffer severe damage owing to excessive deformation. In a previous paper, the energy-based prediction procedure for the peak and cumulative response of a reinforced concrete (RC) frame building with steel damper columns was proposed (Fujii and Shioda, 2023). Although this procedure was verified by comparison to the nonlinear time-history analysis (NTHA) results, the performance of the proposed procedure with pulse-like ground motion records has not been verified yet. In this study, the accuracy of the energy-based prediction procedure for an RC frame building with steel damper columns was investigated by considering pulse-like ground motions. The numerical analysis results reveal that the accuracy of the predicted peak response is satisfactory, which agrees with the results of the author’s previous study. However, the accuracy of the predicted total input energy to the building model depends on the ratio of the pulse period of the ground motion to the effective fundamental period of the building model. The reasons for this underestimation of the total input energy are discussed in this paper.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.

Ultrasonic measurements are used in civil engineering for structural health monitoring of concrete infrastructures. The late portion of the ultrasonic wavefield, the coda, is sensitive to small changes in the elastic moduli of the material. Coda Wave Interferometry (CWI) correlates these small changes in the coda with the wavefield recorded in intact, or unperturbed, concrete specimen to reveal the amount of velocity change that occurred. CWI has the potential to detect localised damages and global velocity reductions alike. In this study, the sensitivity of CWI to different types of concrete mesostructures and their damage levels is investigated numerically. Realistic numerical concrete models of concrete specimen are generated and damage evolution is simulated using the discrete element method. In the virtual concrete lab, the simulated ultrasonic wavefield is propagated from one transducer using a realistic source signal and recorded at a second transducer. Different damage scenarios reveal a different slope in the decorrelation of waveforms with the observed reduction in velocities in the material. Finally, the impact and possible generalizations of the findings are discussed and recommendations are given for a potential application of CWI in concrete at structural scale.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p < 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p < 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.

We present the mathematical model of cooperative functioning of unconscious and consciousness. The model is based on the theory of open quantum systems. Unconscious and consciousness are treated as bio-information systems. The latter plays the role a measurement apparatus for the former. States of both systems are represented in Hilbert spaces. Consciousness performs measurements on the states which are generated in unconscious. This process of unconscious-conscious interaction is described by the scheme of indirect measurements. This scheme is widely used in quantum information theory and it leads to the theory of quantum instruments (Davis-Lewis-Ozawa). Our approach is known as quantum-like modeling. It should be sharply distinguished from modeling of genuine quantum physical processes in biosystems, in particular, in the brain. In the quantum-like framework, the brain is a black box processing information in the accordance with the laws of quantum theory. During the last 10-15 years this framework has been actively used in cognition, psychology, decision making, social and political sciences. The quantum-like scheme of unconscious-consciousness functioning has already been explored for sensation-perception modeling.

Near-fault ground motions can cause severe damage to civil structures, including bridges. Safety assessment of these structures for near fault ground motion is usually performed through Non-Linear Dynamic Analyses, while faster methods are often used. IMPAb (Incremental Modal Pushover Analysis for Bridges) permits to investigate the seismic response of a bridge by considering the effects of higher modes, which are often relevant for bridges. In this work, IMPAb is applied to a bridge case study considering near-fault pulse-like ground motion records. The records were analyzed and selected from the European Strong Motion Database and the pulse parameters were evaluated. In the paper results from standard pushover procedures and IMPAb are compared with nonlinear Response-History Analysis (NRHA), considering also the vertical component of the motion, as benchmark solutions and incremental dynamic analysis (IDA). Results from the case study demonstrate that the vertical seismic action has a minor influence on the structural response of the bridge. Therefore IMPAb, which can be applied considering vertical motion, remains very effective conserving the original formulation of the procedure, and can be considered a well performing procedure also for near-fault events.

A novel coronavirus (2019-nCoV) that is initially found to trigger human severe respiratory illness in Wuhan City of China, 2019, has been recognized as a public health emergency of international concern. In the past two months, this deadly agent has caused 77,785 cases with 2,666 deaths via rapid person-to-person transmission and reached at least 25 countries. However, its evolutionary origin is poorly understood. Here we show integrative evidence that 2019-nCoV is a possible progenitor for SARS-CoV with bat origin. Our finding underscores the importance of tracing origin in the efficient monitoring, and effectively preventing the interspecies transmission of such emerging/re-emerging coronaviruses.

In this paper, we study the third order semilocal convergence of the Newton-like method for finding the approximate solution of nonlinear operator equations in the setting of Banach spaces. First, we discuss the convergence analysis under ω-continuity condition, which is weaker than the Lipschitz and Hölder continuity conditions. Second, we apply our approach to solve Fredholm integral equations, where the first derivative of involved operator not necessarily satisfy the Hölder and Lipschitz continuity conditions. Finally, we also prove that the R-order of the method is 2p + 1 for any p $\in$ (0,1].

Satellite-based remote sensing technologies are utilized extensively to investigate urban thermal environments under rapid urban expansion. Current MODIS data is, however, unable to adequately represent the spatially detailed information because of its relatively coarser spatial resolution, while Landsat data can’t explore temporally the refined analysis due to the low temporal resolution. In order to resolve this situation, we used MODIS and Landsat data to generate “Landsat-like” data by using the flexible spatiotemporal data fusion method (FSDAF), and then studied spatiotemporal variation of land surface temperature (LST) and its driving factors. The results showed that 1) The estimated “Landsat-like” data have high precision; 2) By comparing 2013 and 2016 datasets, LST increases ranging from 1.8°C to 4°C were measurable in areas where the impervious surface area (ISA) increased, while LST decreases ranging from -3.52°C to -0.70°C were detected in areas where ISA decreased; 3) LST has a strongly negative relationship with the Normalized Difference Vegetation Index (NDVI), and a strongly positive relationship with Normalized Difference Built Index (NDBI) in summer; and 4) LST is well correlated with Building density (BD), in a complex conic mode, and LST may increase by 0.460°C to 0.786°C when BD increases by 0.1. Our findings can provide information useful for mitigating undesirable thermal conditions and for long-term urban thermal environmental management.

Objective: To compare the incidence of skin abrasions caused by traditional straight edge flip flop straps versus rolled inner seam (RIS) designs in a controlled laboratory setting using preserved fetal pig skin as a proxy for human skin.Methods: This study utilized a custom-built apparatus to apply friction from two flip flop strap designs to preserved fetal pig skin samples. Three trials were conducted for each strap design to determine the time to initial abrasion onset. A paired t-test was employed for statistical analysis.Results: The RIS design demonstrated a statistically significant delay in abrasion onset compared to the standard design across all trials (p < 0.05), indicating a gentler interaction with the skin.Conclusion: The RIS strap design may offer a beneficial alternative to traditional straps by reducing the friction that can lead to skin abrasions, suggesting a potential to decrease the risk of dorsal foot ulcers. Further studies involving human subjects are warranted to validate these findings in a real-world context.Keywords: Flip flop strap design, skin abrasions, dorsal foot ulcers, footwear design, developing countries, diabetic foot care.

Skin cancer is one of the widespread diseases that typically develop on the skin due to continuous exposure to sunlight. Although cancer can appear on any part of the human body, skin cancer reports account for over half of all cancer occurrences worldwide. There are substantial obstacles to the precise diagnosis and classification of skin lesions because of the morphological variety and indistinguishable characteristics across skin malignancies. Recently, Deep Learning models have been used in the field of image-based lesion diagnosis, and it has demonstrated diagnostic efficiency on par with that of dermatologists. To increase classification efficiency and accuracy for skin lesions, a cutting-edge multi-layer deep Convolutional Neural Network (CNN) termed SkinLesNet has been built in this study. The ResNetV50 and VGG16 models have been carefully compared to review the performance of the proposed model. The dataset used in this study, PAD-UFES-20, contains 1314 samples in total and includes three common forms of skin lesions. The proposed approach, SkinLesNet, significantly outperforms the well-known compared models in the given conditions

Melanoma is widely recognized as one of the most lethal forms of skin cancer, with its incidence showing an upward trend in recent years. Nonetheless, the timely detection of this malignancy substantially enhances the likelihood of patients’ long-term survival. Several computer-based methods have recently been proposed in the pursuit of diagnosing skin lesions at their early stages. Despite achieving some level of success, there still remains a margin of error that the machine learning community considers to be an unresolved research challenge. This study presents a novel framework for the classification of skin lesions. The framework incorporates deep features to generate a highly discriminant feature vector, while also maintaining the integrity of the original feature space. Recent deep models including Darknet53, DenseNet201, InceptionV3, and InceptionResNetV2 are employed in our study for the purpose of feature extraction. Additionally, transfer learning is leveraged to enhance the performance of our approach. In the subsequent phase, the extracted feature information from the chosen pre-existing models is combined, with the aim of preserving maximum information, prior to undergoing the process of feature selection using a novel entropy-controlled grey wolf optimization (ECGWO) algorithm. The integration of fusion and selection techniques is employed to initially incorporate the feature vector with a high level of information and subsequently eliminate redundant and irrelevant feature information. The efficacy of our design is substantiated through the evaluation on three benchmark dermoscopic datasets, namely PH2, ISIC-MSK, and ISIC-UDA. In order to validate the proposed methodology, a comprehensive evaluation is conducted, including a rigorous comparison with established techniques in the field.

Cancer is a condition in which the body's cells proliferate unchecked. Skin cancer is one of the deadliest diseases that impacts the skin on many levels. There are several different types of the disease, including melanoma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanocytic nevus. Due to its increased prevalence, skin cancer, in particular melanoma, is be-coming a serious health problem. Early identification of skin lesions is crucial for successful treatment. Due to their resemblance, many skin lesions are misclassified, which is a severe issue. Researchers seek computer-aided diagnostic tools for early malignant tumor detection. First, a new model based on the combination of "you only look once" (YOLOv5) and "ResNet50" is proposed for melanoma detection with its degree using humans against a machine with 10,000 training images (HAM10000). Second, feature maps integrate gradient change, which allows rapid inference, boosts precision, and reduces the number of hyperparameters in the model, making it smaller. Finally, to get the desired outcomes, the current YOLOv5 model is changed by adding new classes for dermatoscopic images of typical lesions with pigmented skin. The pro-posed approach improves melanoma detection with a real-time speed of 0.4 ms non-maximum suppression (NMS) per image. The performance metrics average is 99.0%, 98.6%, 98.8%, 99.5, 98.3%, and 98.7% for precision, recall, dice similarity coefficient (DSC), accuracy, mean average precision (MAP) from 0.0 to 0.5, and MAP from 0.5 to 0.95, respectively. Compared to cur-rent melanoma detection approaches, the provided approach is more efficient using deep fea-tures.

In recent years, the need to make the built environment more resilient and adaptable to climate change has become increasingly evident. In Europe, this aspect concerns the vast majority of existing buildings, which present several deficiencies from the energy-efficiency point of view, considering they were designed before the introduction of modern energy codes. Nowadays, it is possible to retrofit existing buildings using advanced and high-efficient technologies such as Double Skin Façades (DSFs). The research aims to evaluate the use of properly designed DSFs for the energy restoration of existing buildings. In detail, various DSF configurations are applied to a residential building located in central Italy and investigated under present and future climate conditions, estimated through regional climate models. The results underline that all the analysed Double Skin Façades confirm to be a useful option, and, in particular, the Multi-Storey typology allows drastic energy needs decrement. Moreover, the general increase in temperatures and solar radiations could affect the building energy performance, and the insertion of DSF can mitigate the climate change effects, reducing the predicted energy consumption and ensuring better behaviours than the building in its original state.

Almond beverages are gaining ever-increasing consumer preference in the growing market of non-alcoholic vegetable beverages, ranking in first place among oilseed-based drinks, mainly due to the perceived healthy benefits. However, the high cost of the raw material, time and energy consuming pre-treatments such as soaking, blanching and peeling, and post-treatments such as thermal sterilization, leading also to the loss of valuable macronutrients and micronutrients, hinder the sustainability, affordability and spread of almond beverages. Hydrodynamic cavitation processes were applied, as a single-unit operation, to the extraction in water of almond skinless kernels in the form of flour and fine grains, and to whole almond seeds in the form of coarse grains, up to high concentrations. The results showed full compliance with a high-end commercial product and with the expected levels based on the properties of the raw materials. The concentrated extract obtained from whole almond seeds showed a comparatively much higher antiradical activity, likely due to the contribution of the almond kernel skin. In conclusion, hydrodynamic cavitation could represent a convenient alternative processing route to the production of conventional and new integral almond beverages, avoiding multiple and costly technological steps, while affording fast production cycles of potentially healthier beverages.

Chronic oxidative stress in long-distance runners adversely affects conditioning. Therefore, it is important to objectively assess and monitor oxidative stress but measuring oxidative stress can be invasive or require skill to measure. Therefore, this study aimed to verify whether skin autofluorescence (SAF), a noninvasive, rapid, and easily calculable metric for calculating advanced glycation end products (AGEs), is useful as an oxidative stress biomarker. The subjects were 50 young Japanese male long-distance runners (aged 20.2 ± 1.2 years); 35 average male university students (aged 19.8 ± 1.1 years) served as controls. The interactions and relationships between SAF and plasma pentosidine and oxidative stress markers (reactive oxygen metabolite-derived compounds [d-ROMs], biological antioxidant potential [BAP], and the BAP/d-ROMs ratio) in runners were examined, and SAF in the runners and controls was compared. The results suggest that plasma pentosidine in runners is associated with oxidative stress markers and that plasma pentosidine can assess oxidative stress. However, SAF was not validated as an oxidative stress marker because it was not associated with oxidative stress marker. In future, clarifying the factors affecting SAF may clarify the relationship between SAF, plasma pentosidine, and oxidative stress markers.

Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to the overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of oily skin and acne with botulinum neurotoxin type A.

The Galvanic Skin Response (GSR, also widely known as electrodermal activity EDA) is one of the signals related to this emotional reaction. Given the sparsity of studies related to and the variety of devices, we experimented at the Human Health Activity Laboratory with 17 healthy subjects. The goal is to know the variability of detection changes in the electrodermal activity among a test group with heterogeneous respondents in response to valence and arousal stimuli, correlating GSR biosignals measured from different body sites. We experiment with the right and left wrist, left fingers, the right foot's inner side using Shimmer3GSR, and Empatica E4 sensors. Results indicate as the most promising homogeneous GSR measure place the left fingers and right foot. Results suggest that due to a significantly strong correlation among the inner side of the right foot and left fingers and moderate correlations with the right and left wrist, the foot is a good place to measure EDA. This paper also contributes knowledge about some wearable sensor technologies available in the market. Shimmer3GSR sensor may be better reliable to homogenous detecting electrodermal activity changes, as these have fewer anomalies among the respondents. However, we found some anomalies in signals from the Empatica E4 sensor, which we discuss in this work.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

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

In this work, we incorporate a thixotropic-viscoelastic model into the widely used Computational Fluid Dynamics (CFD) software OpenFOAM, along with the rheoTool library. The model we implement is known as the Modified-Bautista-Manero (MBM), and effectively describes the rheological behavior of worm-like micellar solutions in extensional flows. We provide a detailed explanation of the numerical implementation of the model, specifically using the log-conformation tensor approach. Unlike previous works focused on this kind of fluids, we simulate inertial flows while considering convective terms in the governing equations, thus obtaining a more realistic behavior on the calculated results. The MBM model implementation is validated through numerical simulations on two different industrial-relevant geometries: the planar 4:1 contraction and the 4:1:4 contraction-expansion configurations. Furthermore, we investigate the influence of inertial, viscoelastic, and thixotropic effects on various flow field variables. These variables include velocity, viscosity, normal stresses, and corner vortex size. Our analysis encompasses both transient and steady solutions of corner vortexes across a range of Deborah and Reynolds numbers. Our results are also directly compared with simulations obtained using the non-thixotropic rubber network-based exponential Phan-Thien-Tanner (EPTT) model. From our planar 4:1 contraction results, we found that vortex-enhancement is seen when high elasticity is coupled with quick structural reformation and very low inertial effects. From our planar 4:1:4 contraction-expansion simulations, we show that an increase in inertia leads both to vortex-inhibition in the upstream channel and slight vortex-enhancement in the downstream channel. Lastly, we show the strong effect of the convection of fluidity into the fluidity profiles and into the upstream/downstream corner vortex sizes.

Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attrac-tion in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogues; molecules similar to natural sub-strates of numerous fungal enzymes and Quorum Sensing signaling molecules of fungi and yeast; etc. Most part of the review is devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the cur-rent scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

Background: Obtaining adipose-derived stem cells is limited by its capacity to differentiate. Stimulation by platelet-rich fibrin appears to have the beneficial effects to accelerate differentiation. Objective: To obtain immunohistochemistry evidence of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells. Methods: We used post-test only controlled-group design. Adipose-derived stem cells were isolated and cultured until 4 passages in α-MEM culture medium. Results: GATA-4 expression increased in platelet-rich fibrin group compared with control group (68.20±6.82 vs 58.15±1.23 counts; p<0.05; 68.20±6.82 vs 52.96±2.02 counts; p<0.05). Troponin expression also increased in platelet-rich fibrin group (50.66±7.2 vs 10.73±2.39 counts; p<0.05; 50.66±7.2 vs 26.00±0.4 counts; p<0.05). Conclusion: There is an immunohistochemistry benefit of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells into cardiomyocyte-like cells.

Filamentous manganese (Mn) oxide particles, which occur in the suboxic zone of stratified waterbodies, are important drivers of diverse elemental cycles. Although these particles are considered to be bacteriogenic, the environmental factor responsible for their formation has not been identified. Based on this study of laboratory cultures of a model Mn(II)-oxidizing bacterium, the supply of algal extracellular polymeric substances (EPS) was shown to stimulate Mn(II) oxidation and thus the production of filamentous Mn oxide particles. This observation was consistent with results obtained for naturally occurring particles collected from a near-bottom layer (depth of ~90 m) in the northern basin of Lake Biwa, Japan, that is, most Mn particles resembling delta-MnO2 were associated with an EPS-like gelatinous matrix, which contained dead algal cells and was lectin-stainable. In the lake water column, EPS produced by photosynthesis sank to the bottom layer. The analysis of the quality of water samples, which have been collected from the study site for 18 years, reveals that the annual average total phytoplankton biovolume in the surface layer correlates with the density of filamentous Mn particles in the near-bottom layer. Among different phytoplankton species, green algae appeared to be the key species. The results of this study suggest that algal EPS production induces the formation of filamentous Mn oxide particles in the near-bottom layer of the northern basin of Lake Biwa.

RNA interference is a highly conserved process in which non-coding small RNAs (sRNA) modulate gene expression at the post-transcriptional level influencing plant growth and development. Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) are the core elements involved in gene silencing and their gene families have been explored in many plants. However, these genes and their response to abiotic stresses have not yet been well in wheat. In this study, 82 AGO, 31 DCL, and 31 RDR genes were identified and phylogenetic analysis of these proteins showed that clustered into ten, four and four clades respectively. RNA-seq analysis revealed constitutive expression of AGO1, AGO9, and DCL2 family expression analysis in tissues under normal and stress conditions, whereas RDR1 which is known to engage in siRNA biogenesis showed higher expression levels in wheat leaf tissues. Our findings build the foundation for comparative genomics analyses of RNA silencing elements in cereal crops, as well as new insights into the functional complexity of RNA silencing in wheat stress responses, which is critical for understanding the processes underlying wheat stress responses.

Understanding the complex interactions between metabolism and the immune system (“meta-flammation”) is crucial for the identification of key immunomodulatory factors as potential therapeutic targets in obesity and in cardiovascular diseases. Cathelicidin antimicrobial peptide (CAMP) is an important factor of innate immunity and is expressed in adipocytes. CAMP therefore might play a role as an adipokine in metaflammation and adipose inflammation. Toll-like receptor (TLR) 9 is another component of the innate immune system that is expressed and functionally active in adipocytes. The aim of the present study was to investigate the impact of TLR9 signaling on CAMP expression in adipocytes and in adipose tissue. CAMP gene expression in murine 3T3-L1 and human SGBS adipocytes and in murine and human adipose tissues was quantified by real-time PCR. TLR9 knockdown was applied in murine 3T3-L1 adipocytes via siRNA transfection. Adipocyte inflammation was induced in vitro by TNFα stimulation. Serum CAMP concentrations in TLR9 knockout (KO) and in wildtype mice were quantified by ELISA. CAMP gene expression was considerably increased in 3T3-L1 adipocytes during differentiation. TNFα significantly induced CAMP gene expression in mature adipocytes, which was antagonized by inhibitors of NF-κB and PI3K signaling. Cell-free nucleic acids (cfDNA) as endogenous TLR9 ligand significantly impaired CAMP gene expression, whereas synthetic agonistic and antagonistic TLR9 ligands had no effect. Cellular TLR9 knockdown reduced adipocyte CAMP gene expression in vitro and male TLR9 knockout mice exhibited lower systemic CAMP concentrations than wildtype mice. CAMP and TLR9 gene expression were correlated positively in murine and human subcutaneous but not in intraabdominal/visceral adipose tissues. These findings suggest a regulatory role of TRL9 in adipocytic CAMP expression as a novel putative molecular mechanism in adipose tissue innate immunity.

Spiral steroids (SS) are a newly discovered type of steroid. Originally, they were described as cardiotonic glycosides because they cross-reacted with digoxin-specific antibodies (Digoxin-Like-Materials-DLM). SS differ from the classical steroids in several ways: [a] they are steroid phosphodiester conjugates and displace digoxin from digoxin-specific antibodies, [b] in contrast to all other steroids, cholesterol is not a precursor, [c] SS have more than 21 carbon atoms; the extra atoms form a 5th ring which includes a lactone, [d] SS bind to NaK-ATPase in membranes rather than receptors in the nucleus. SS have been identified by HPLC- mass spectroscopy in extracts from mammals, birds, and oysters but were not detected in plant extracts. Overall, SS seem to be key components in regulating potassium electrolytes during pregnancy and its related diseases – specifically pre-eclampsia and necrotizing enterocolitis.

This paper attempts to describe the large-scale (solar system-like, astronomical-scale) systems of the known world using the physical models and mathematical tools of relativistic quantum mechanics. The value of H_x can be introduced and approximated as an analogue of the constant ℏ. Based on the quantum mechanical approach, the proper time scale of the solar system can be determined.

Background: There is several challenges to solve irreversible loss of cardiomyocytes due to myocardial infarction. Cell therapy is believed as an ideal treatment for cardiac regeneration in the infarct area. Obtaining adipose-derived stem cells increases seems to be promising, however it is limited by the capacity to differentiate. Stimulation by injectable platelet-rich fibrin appears to have the beneficial effects to accelerate cardiomyocyte-like cells differentiation. Objective: To analyse the benefit of injectable platelet-rich fibrin to accelerate differentiation of adipose-derived mesenchymal stem cells into cardiomyocyte-like cells. Methods: This study is a true experimental randomized post-test design study. Adipose-derived mesenchymal stem cells were isolated from adipose tissues and cultured until 4 passages. The characteristics of adipose-derived mesenchymal stem cells were measured by the expression of CD 34-, CD 45-, and CD 105+ using flowcytometry. The samples were divided into 3 groups, i.e. negative control (α-MEM), positive control (differentiation medium) and treatment group (platelet-rich fibrin). The assessment of GATA-4 marker expression was conducted using flowcytometry on the fifth day and troponin was conducted using immunocytochemistry on the tenth day to determine the differentiation to cardiomyocyte. Data analysis was conducted using T-test and One-Way ANOVA on normally distributed data determined through Shapiro-Wilk test. Results: Flowcytometry on GATA-4 expression revealed significant difference on addition of platelet-rich fibrin compared with negative and positive controls (68.20 ± 6.82 vs 58.15 ± 1.23; p<0.05; 68.20 ± 6.82 vs 52.96 ± 2.02; p<0.05). This was supported by the results of immunocytochemistry on troponin expression which revealed significant difference between platelet-rich fibrin group compared with negative and positive controls (50.66 ± 7.2 vs 10.73 ± 2.39; p<0.05; 50.66 ± 7.2 vs 26.00 ± 0.4; p<0.05). Conclusion: Injectable platelet-rich fibrin has beneficial effect to accelerate differentiation of adipose-derived mesenchymal stem cells into cardiomyocyte-like cells.

There is an overarching need to find alternative treatment options for malaria and this quest is more pressing in current times due to the morbidity and mortality data arising from most endemic countries and partially owing to the fact that the SARS-Cov-2 pandemic has diverted much public health attention. Additionally, the therapeutic options available for malaria has been severely threatened with the emergence of resistance to almost all existing drugs by the human malaria parasite. The Artemisinin Combination Therapies (ACTs) which hitherto have been the mainstay for malaria have encountered resistance in South East Asia, a notorious ground zero for the emergence of antimalarial drug resistance. This review analyses few key druggable targets of the parasite and the potential to leverage strategic inhibitors to mitigate the scourge of malaria by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Furthermore, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage such findings for antimalarial drug production.

Poly(2-methoxyethyl acrylate) (PMEA) and poly(ethylene oxide) (PEO) have protein-antifouling properties and blood compatibility. ABA triblock copolymers (PMEAn-PEO11340-PMEAn (MEOMn)) were prepared using single-electron transfer-living radical polymerization (SET-LRP) using a bi-functional PEO macroinitiator. Two types of MEOMn composed of PMEA blocks with a degree of polymerization (DP = n) of 85 and 777 were prepared using the same PEO macroinitiator. MEOMn formed flower micelles with a hydrophobic PMEA (A) core and hydrophilic PEO (B) loop shells in diluted water with a similar appearance to petals. The hydrodynamic radii of MEOM85 and MEOM777 were 151 and 108 nm, respectively. The PMEA block with a large DP formed a tightly packed core. The aggregation number (Nagg) of the PMEA block in a single flower micelle for MEOM85 and MEOM777 was 156 and 164, respectively, which were estimated using a light scat-tering technique. The critical micelle concentrations (CMCs) for MEOM85 and MEOM777 were 0.01 and 0.002 g/L, respectively, as determined by the light scattering intensity and fluorescence probe techniques. The size, Nagg, and CMC for MEOM85 and MEOM777 were almost the same inde-pendent of hydrophobic DP of the PMEA block.

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. The LKs act on G-protein coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (ABLKs) of the abdominal neuromeres coexpress LK and a diuretic hormone (DH44), and together these regulate water and ion homeostasis and associated stress, as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses, and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs, in the brain express LK in larvae, but inconsistently so in adults. These ALKs coexpress three other neuropeptides and regulate water and ion homeostasis, feeding and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.

We continue to analyze basic constraints on human's decision making from the viewpoint of quantum measurement theory (QMT). As has been found, the conventional QMT based on the projection postulate cannot account for combination of the question order effect (QOE) and the response replicability effect (RRE). This was an alarm signal for quantum-like modeling of decision making. Recently, it was shown that this objection to quantum-like modeling can be removed on the basis of the general QMT based on quantum instruments. In the present paper we analyse the problem of combination of QOE, RRE, and the famous QQ-equality (QQE). This equality was derived by Busemeyer and Wang and it was shown (in the joint paper with Solloway and Shiffrin) that statistical data from many social opinion polls satisfies it. Now, we construct quantum instruments satisfying QOE, RRE, and QQE. The general features of our approach are formalized with postulates which generalize {\it Wang-Busemeyer} postulates for quantum-like modeling of decision making. Moreover, we show that our model closely reproduces the statistics of the famous Clinton-Gore Poll data with a prior belief state independent of the question order. This model successfully removes the order effect from the data to determine the genuine distribution of the opinions in the Poll. The paper also provides a psychologist-friendly introduction to the theory of quantum instruments - the most general mathematical framework for quantum measurements. We hope that this theory will attract attention of psychologists and will stimulate further applications.

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC₅₀ value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

Skin and soft-tissue infections (SSTI) are common cases of hospital-acquired infections with aetiologic agents exhibiting antimicrobial resistance (AMR). We determined the prevalence, proportion of laboratory-investigated cases, AMR-profiles, and factors associated with SSTI and multi-drug resistance (MDR). This study was based on archived data of patients suspected of SSTI from 2019-2021 at Jinja Regional Referral Hospital. The analysis involved 268 randomly selected patient reports. Prevalence of SSTI was 66.4%. Laboratory-investigated cases were 14.11%. Staphylococcus aureus (n=51) was the most isolated organism. MDR pathogens explained 47% of infections. Methicillin-resistant S. aureus was up to 44%. In addition, 61% of Gram-negatives had the potential to produce extended-spectrum beta-lactamases, while 27% were non-susceptible to carbapenems. Ward of admission was significantly associated with infection (aPR=1.78, 95% CI: 1.003-3.18, p-value=0.04). Age category (19-35) was an independent predictor for MDR infections (aPR=2.30, 95%CI:1.02-5.23, p-value=0.04). The prevalence is relatively high with MDR pathogens responsible for almost half of the infections. Routine use of culture and sensitivity testing should be done for proper infection management. Gentamicin and ciprofloxacin can be considered for empirical management of emergency SSTI suspected of S. aureus. Recognizing SSTI under the Global Antimicrobial resistance Surveillance System would lead to improved preparedness and response to AMR.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa and Latin America, and in different ethnic groups. In recent years, more attention on AD heterogeneity associated on multiple factors, including patient’s ethnic background, has been posed, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineate differences among racial groups with AD. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, while very rarely in Africans. The Th2 activation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal whereas African Americans own a strong Th2/Th22 signature and the absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity may own important therapeutic implications as the genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting the investigation about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity of pathophysiology across ethnicities and its potential therapeutic implications.

Wounds represents a medical problem that contribute importantly to patient morbidity and to the healthcare costs in several pathologies. In Hidalgo, Mexico, Bacopa procumbens plant has been traditionally used for wound healing care for several generations; in vitro and in vivo experiments were design to evaluate the effects of bioactive compounds obtained from B. procumbens aquoethanolic extract and to determine the key pathways involved in wound regeneration. Bioactive compounds were characterized by HPLC- QTOF-MS and proliferation, migration, adhesion, and differentiation studies were done on NIH/3T3 fibroblasts. Polyphenolic compounds from Bacopa procumbens (PB) regulated proliferation and cell adhesion; enhanced migration reducing the artificial scratch area; and modulated cell differentiation. PB compounds were included in a hydrogel for topical administration on rat excision wound model. Histological, histochemical and mechanical analysis showed that PB treatment accelerates wound closure in at least 48 h; reduce inflammation, increasing cell proliferation and deposition and organization of collagen in earlier times. These changes resulted in the formation of a scar with better tensile properties. Immunohistochemistry and RT-PCR molecular analyses demonstrated that treatment induces: i) overexpression of transforming growth factor beta (TGF-β); and ii) the phosphorylation of Smad 2/3 and ERK1/2, suggesting the central role of some PB to enhance wound healing, modulating TGF-β activation.

In the recent years, tissue engineering researchers have exploited a variety of biomaterials that can potentially mimic extracellular matrix (ECM) for tissue regeneration. Natural cellulose, mainly obtained from bacterial (BC) and plant-based (PC) sources, can serve as a high potential scaffold material for different regenerative purposes. Natural cellulose has drawn the attention of researchers due to its advantage over synthetic cellulose in terms of availability, cost-effectiveness, perfusablility, biocompatibility, negligible toxicity, mild immune response and due to imitating native tissues. In this article, we will review the recent in vivo and in vitro studies aimed to assess the potentials of natural cellulose for the purpose of soft (skin, heart, veins, nerve, among others) and hard (bone and tooth) tissue engineering.

In contemporary design practices, there is a disconnect between the design techniques used for early-stage design experimentation and performance analysis, and those used for the manufacture and construction. This study addresses the problems in developing an integrated digital design workflow and provides a research framework for integrating environmental performance requirements with robotic manufacturing processes on a construction site. The proposed method enables the user to import a design surface, identify design parameters, set several environmental performance goals, and thereafter simulate and select a robotic building strategy. Based on these inputs, design alternatives are developed and evaluated, considering their robotically simulated constructibility, in terms of their performance criteria. To validate the proposed method, the design is evaluated in an experiment wherein a double-skin facade perforation is generated using the proposed methodology. The results suggest a heuristic feature to improve the simulated robotic constructibility. Moreover, the functionality of the prototype is demonstrated.

In contemporary design practices, there is a disconnect between the design techniques used for early-stage design experimentation and performance analysis, and those used for the manufacture and construction. This study addresses the problems in developing an integrated digital design workflow and provides a research framework for integrating environmental performance requirements with robotic manufacturing processes on a construction site. The proposed method enables the user to import a design surface, identify design parameters, set several environmental performance goals, and thereafter simulate and select a robotic building strategy. Based on these inputs, design alternatives are developed and evaluated, considering their robotically simulated constructibility, in terms of their performance criteria. To validate the proposed method, the design is evaluated in an experiment wherein a double-skin facade perforation is generated using the proposed methodology. Initial results suggest a heuristic feature to improve the simulated robotic constructibility. Moreover, the functionality of the prototype is demonstrated.

Mitochondrial disorders, although heterogeneous, are traditionally described as conditions characterized by encephalomyopathy, hypotonia and progressive postnatal organ failure. Here we provide a systematic review of Linear Skin Defects with Multiple Congenital Anomalies (LSDMCA), a rare unconventional mitochondrial disorder which presents as a developmental disease; its main clinical features include microphthalmia with different degrees of severity, linear skin lesions, and central nervous system malformations. The molecular basis of this disorder has been elusive for several years. Mutations were eventually identified in three X-linked genes, i.e., HCCS, COX7B, and NDUFB11, which are all endowed with defined roles in the mitochondrial respiratory chain. A peculiar feature of this condition is its inheritance pattern: X-linked dominant male-lethal. Only female or XX male individuals can be observed, implying that nullisomy for these transcripts is incompatible with normal embryonic development in mammals. All three genes undergo X-inactivation that, according to our hypothesis, may contribute to the extreme variable expressivity observed in this condition. We propose that mitochondrial dysfunction should be considered as an underlying cause in developmental disorders. Moreover, LSDMCA should be taken into consideration by clinicians when dealing with patients with microphthalmia with or without associated skin phenotypes.

In today's world it is very much important to maintain the security of information and its risks. The biometric-based techniques are very much useful in these problems. Among the several kinds of biometric-based technique, face detection is much complex and much more important. Due to the age and several other problems, a human face structure changes over time, again a human has lots of expressions. Sometimes due to the lighting condition or the variation of the angle of an input device, the pattern of a human face structure also changed. As a result, the face cannot be detected properly. In this paper, a method is proposed that can detect the human faces both automatically and manually very efficiently. In manual mode, a user can select the input faces referred by the system according to their choice. In automated mode, the system detected all possible face areas using the Kohonen Self-Organizing Feature Map technique. This method reduced the complex color image into a vector quantized image with desired colors. Then a color segmentation technique is used to detect the possible face skin areas from the vector quantized image. Then the Histogram Oriented Gradient technique used to detect the feature from the faces and K-Nearest Neighbour Classifier is used to compare both face images detected by the two modes. The automated method prosed better accuracy than the manual method.