Poikilodermatous plaque-like hemangioma (PPH) is a recently described clinical and pathological entity, with only 18 cases reported in the literature. Although uncommon, this benign condition presents consistent clinical and histological findings. We present a new case of PPH in an 81-year-old male and review the existing literature. The persistence over time and the need to distinguish PPH from more significant lesions underscore the importance of its clinical and pathological recognition.

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, trithorax complex, PR-DUB, SRC1, HP1α, and BET proteins), and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.

Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and marketed. Virus-like particles (VLPs) have emerged as promising alternatives to most explored nanoparticles because of the absence of viral genetic material, their incapacity to replicate, mimicry of viral structure, and tropism conservation. Furthermore, VLPs can be surface functionalized with small molecules to improve circulation half-life and target specificity. Through the functionalization and coating of VLPs, it is possible to optimize the response properties to a given stimulus, such as heat, pH, an alternating magnetic field, or even enzymes. Surface functionalization can also modulate other properties, such as biocompatibility, stability, and specificity, deeming VLPs as potential vaccine candidates or delivery systems. In this review, we address the different types of functionalization of VLPs, their importance, and their consequent biomedical applications.

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Hence, there is a need to discover innovative therapeutic approaches to counteract DOX-induced cardiotoxicity (DIC). MSC-Exos have shown to reduce apoptosis and cardiac fibrosis and promote cardiomyocyte proliferation in myocardial infracted mice. However, the effect of MSC-Exos on ameliorating DOX-induced pyroptosis has not been investigated. In this current study H9c2 were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. Our data depicted that post-treatment with MSC-Exos significantly (p<0.05) reduced the HMGB1/TLR4 axis, inflammasome formation (NLRP3), pyroptotic markers (caspase-1, IL-1β, and IL-18), and the pyroptotic executioner (GSDMD) in DOX-treated H9c2 cells. In conclusion, our data shows that MSC-Exos attenuates inflammation-induced pyroptosis in our in vitro DIC model. Our findings indicate that MSC-Exos may serve as a promising therapeutic intervention for mitigating DIC, as they maintain the therapeutic capabilities of MSCs while circumventing the drawbacks associated with traditional stem cell therapy.

The recycling of common soda-lime glass (SLG) is far from being complete, since the material may contain small polymeric, metallic and ceramic contaminations. This has a negative impact on the quality of new glass articles prepared via re-melting. Alternatively, the full reuse of contaminated cullets could be achieved by low-temperature consolidation into geopolymer-like materials. SLG powders, used either as received or pre-washed in acid solution, were added to a sodium aluminate solution at the room temperature for 3 h, under low-speed mechanical stirring. Microporous semi-crystalline monoliths were formed by the casting of suspensions in plastic molds and cured at 75°C overnight. The monoliths featured hydrosodalite as the main crystalline phase for as received SLG and LTA zeolite in the case of pre-washed SLG. The mechanical properties compared well with those of cementitious materials. Moreover, by addition of coarse glass particles as fillers, the methodology successfully yielded Venetian terrazzo-like samples, which could lead to significant material and energy savings in their manufacture. The proposed approach could also be extended to other difficult-to-reuse glass formulations and provide attractive and versatile up-cycled materials.

In this article, we analyze the thermodynamics, thermal fluctuations and quasi-normal modes of a torus-like charge AdS black hole. The parameters of a torus-like charged AdS black hole are its mass, electric charge, and cosmological constant. We used a torus-like charge AdS black hole to evaluate thermodynamics through thermal fluctuations and found that it significantly affected the corrected thermodynamic potentials. Black holes of larger radii are more stable and significant. The effect of thermal fluctuation has been investigated on the other thermodynamic potentials such as the Hemohltz free energy, Gibbs free energy, enthalpy, and specific heat, using the concept of corrected entropy. Finally, we use null geodesics to deal with quasi-normal modes. The null geodesics provide the photon sphere angular velocity and Lyapunov exponent, which are the real and imaginary components of the quasi-normal modes in the eikonal limit. With inceasing charge and photon radius, angular velocity reaches its maximum, similar to Lyapunov's exponent.

KLFs seem to associate with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of differentiation of cardiac myofibroblasts or a modified fatty acid oxidation, related to the formation of a dilated cardiomyopathy; myocardial infarctions, left ventricular hypertrophy and diabetic cardiomyopathies. MicroRNA have been involved in certain regulatory loops of KLFs as they may function as critical modulators of vascular smooth muscle cells in atherosclerosis, in heart failure and as markers of endothelial damage in acute myocardial infarction.

This study deals with vibrational and crystallographic aspects of the thermally induced transformation of serpentine-like garnierite into quartz, forsterite, and enstatite occurring at about 620 °C. Powder specimens of garnierite have been annealed in static air between room temperature and 1000 °C. The resulting products from the transformations detected based on thermogravimetric and differential thermal analysis, have been extensively characterized via microRaman spectroscopy, and X-ray diffraction. Our study shows that serpentine-like garnierite consists of a mixture of different mineral species. Furthermore, these garnierites and their composition can provide details based on the mineralogy and the crystalline phases resulting from the thermal treatment.

In this paper, by considering Einstein-Hilbert-Bumblebee (EHB) gravity around global monopole field, we derive exactly a black hole spacetime metric. To test the effect of global monopole field and bumblebee field, which causes the spontaneous Lorentz symmetry breaking, we calculate the weak deflection angle using the Gauss-Bonnet theorem.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

Real-time evolution of the electron densities under excitations in La₂CuO₄ was calculated by the time-dependent density functional theory (TDDFT). The author found, for the first time, under excitations, the electron cloud of Cu²⁺ changes obviously and the characteristic frequencies are 83 meV and 36 meV, respectively, for two different modes. The results are unexpected and close to that of lattice vibrations. The results show that the electron cloud of Cu²⁺ (just like the lattice) can be the electron-pairing medium in high temperature copper oxide superconductors.

Changes in curricula, publication policy and information technology, notably in China have led to concentrations in the role of STEM (science, technology, engineering and mathematics) education in early childhood and applauded to proliferations of imported up-to-date reading materials and mobile apps in English. This paper proposes a longitude study of a Chinese toddler learning STEM by reading picture books and playing with tablet and suggests new horizons in parenting and in STEM education during children's early years. The present study carried out from 2016, when the participant reached one year old, eligible to learn to speak and to concentrate on the picture books read by parents who had filled a language background questionnaire with information on themselves and the participant. Tablet playing brought about for the two-year-old toddler and collections of STEM books in English was added for the second year. Data collection lasted for two years with an iLab video camera, capturing utterances and motions for five minutes per week transcribed by VoiceScript software. Tests were given quarterly at private home by tapping in mobile app "Bilingual Child Learning" which consists of 20 basic STEM themes before scores were collected. Findings indicate that (1) it is accessible for children of very early years to be engaged in English STEM resources, (2) kids' limited English dominance does not impede learning STEM, (3) and to think in English in early STEM contributes to children's English.

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].

The misfolding and aggregation of proteins is the neuropathological hallmark of numerous diseases including Alzheimer’s disease, Parkinson’s disease, and prion diseases. It is believed that misfolded and abnormal -sheets forms of wild-type proteins are the vectors of these diseases by acting as seeds for the aggregation of endogenous proteins. Cellular prion protein (PrPC) is a glycosyl-phosphatidyl-inositol (GPI) anchored glycoprotein which is able to misfold to a pathogenic isoform PrPSc, the causative agent of prion diseases which present as sporadic, dominantly inherited and transmissible infectious disorders. Increasing evidence highlight the importance of prion-like seeding as a mechanism for pathological spread in Alzheimer’s disease and tauophaty, as well as other neurodegenerative disorders. Here, we report the latest findings on the mechanisms controlling protein folding, focusing on the ER quality control of GPI-anchored proteins and describe the “prion-like” properties of amyloid- and tau assemblies. Furthermore, we highlight the importance of pathogenic assemblies interactions with protein and lipid membrane components and their implications in both prion and Alzheimer’s diseases.

Objective: Health/wellness applications on mobile devices (Apps) may positively affect the health of seniors (persons age 65+). But for an App to promote health in its target audience, it must achieve meaningful use. Method: For one and a half years, residents at a Life Plan Community (mean age 86) used a wellness App running on iPad. In a digital survey, residents rated their overall satisfaction with the App on a scale from 1 (strongly dislike) to 10 (strongly enjoy). Results: User satisfaction (96 respondents of 252; 38% response rate) was distributed with maximum 8, median 7, mean 6.6, and standard deviation 2.3. Discussion: The results suggest that it is feasible to inspire seniors to pursue whole-person wellness using an App: technology may promote “active aging.”

Globin-like superfamily constitutes a superfamily of both extracellular and intracellular proteins that are found in 3 kingdoms of life. Globins are respiratory proteins that usually bind an oxygen molecule .Earlier, phylogenetic study of globin like superfamily was based on morphological character, however, molecular basis of their functional diversity is not completely understood. The present study focuses on the phylogenetic analysis of globin at molecular level. Firstly, proteins of SCOP families of globin like superfamily were retrieved from NCBI and then similar proteins are retrieved from PSI BLAST results and then pfam was used to predict the domains and two domains: Globin and Phycobilisome were analysed. Other analysis predicted the localization in cytoplasm of most of the proteins. The nucleotide sequences of same species for protein analysis were retrieved from NCBI, and phylogenetic analysis of aligned fasta files of proteins and nucleotides by using MEGA at molecular level was performed and analysis shows the difference on taxonomic tree and phylogenetic tree.

Pathogenic Salmonella strains have a set of virulence factors allowing them to generate systemic infections and damage in a variety of hosts. Among these factors, bacterial proteins secreted by specialized systems are used to penetrate the host’s intestinal mucosa, through the invasion and destruction of specialized epithelial M cells in the intestine. On the other hand, numerous studies have demonstrated that humans, as well as experimental animal hosts, respond to Salmonella infection by activating both innate and adaptive immune responses. Here, through live cell imaging of S. Typhimurium infection of zebrafish larvae, we showed that besides the intestinal colonization, a deformed cloacae region and a concomitant accumulation of S. Typhimurium cells was observed upon bacterial infection. The swelling led to a persistent inflammation of infected larvae, although the infection was non-lethal. The in vivo inflammation process was confirmed by the co-localization of GFP-tagged S. Typhimurium with mCherry-tagged neutrophils at 72 hours post exposition. Our live-cell analyses suggest that Salmonella Typhimurium induce cloacitis-like symptoms in zebrafish larvae. Typhimurium induce cloacitis-like symptoms in zebrafish larvae.

Background: The goal of this study was to evaluate the effect of Extracorporeal Membrane Oxygenator (ECMO) on mortality in patients with cardiogenic shock excluding Impella and IABP use. Method: The large Nationwide Inpatient Sample (NIS) database was utilized to study any association between the use of ECMO in adults over age of 18 on mortality and complications with a diagnosis of cardiogenic shocks. Results: ICD-10 codes for ECMO, and cardiogenic shock for available years 2016-2020 were utilized. A total of 796,585 (age 66.5±14.4) patients had a diagnosis of cardiogenic shock excluding Impella. 13,160 (age 53.7±15.4) were treated with ECMO without IABP. Total inpatient mortality without any device was 32.7%. It was 47.9% with ECMO. Using multivariate analysis adjusting for 47 variables such as age, gender, race, lactic acidosis, three-vessel intervention, left main myocardial infarction, cardiomyopathy, systolic heart failure, acute ST-elevation myocardial infarction, peripheral vascular disease, chronic renal disease, etc., ECMO utilization remained highly associated with mortality (OR: 1.78, CI: 1.6-1.9, p<0.001). Evaluating teaching hospitals only revealed similar findings. Major complications were also high in ECMO cohort. Conclusion: In patients with cardiogenic shock, the use of ECMO was associated with the high in hospital mortality regardless of comorbid condition, high-risk futures, or type of hospital.

Respiratory distress syndrome (RDS) is a major respiratory morbidity associated with prematurity. In this case-control study, we prospectively evaluated whether targeted metabolomic analysis (gas chromatography–mass spectrometry) of the gastric fluid obtained from very preterm neonates (< 32 weeks’ gestation) during the first hour after birth could predict the need for exogenous surfactant for the treatment of RDS. 43 infants with RDS necessitating surfactant (cases) were compared with 30 infants with mild or no RDS (controls) who were not treated with surfactant. Perinatal and neonatal characteristics were recorded. Univariate analysis showed significant differences between the two groups in gastric fluid metabolites (L-glycine and acetyl-L-serine) and clinical parameters (gestational age, 1- and 5-minute Apgar scores, and intubation in the delivery room). Moreover, multivariate analysis revealed intubation in the delivery room as the most potent clinical predictor of surfactant administration [AUC of 0.69 (95% CI 0.57-0.81)]. The combination of metabolomic and clinical data allowed for the construction of a model with good accuracy [AUC 0.76 (95% CI 0.64-0.86)] in predicting surfactant replacement therapy. Further research is required to explore the role of gastric fluid metabolomics in the prediction of RDS and other neonatal outcomes.

Engineering application of additively manufactured (AM) metallic materials is quite limited by their fatigue behaviors which are very inconsistent with that of conventionally wrought or cast ones. Here, based on advanced material characterization techniques, such as focused ion beam (FIB), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the mi-crostructures underneath fracture surfaces were thoroughly investigated in an AM aluminium (AlSi10Mg) alloy with horizontal and vertical building orientation endured very-high-cycle fa-tigue (VHCF) loading under stress ratios R = –1, 0 and 0.5. Two VHCF failure specimens A and B were representatively selected to further SEM examine and TEM samples preparation via FIB milling. Specimen A was horizontally printed and failed at R = –1; specimen B was vertically printed and failed at R = 0. TEM samples A1 and B1 were lifted from locations near the crack ini-tiation sites on the fracture surfaces of specimens A and B; The locations of TEM samples A2 and B2 kept away from the crack origin sites but still within the “fish-eye” region of crack steady growth. TEM observations show that there was no characteristic microstructure induced by VHCF in different oriented specimens and under various R values.

This randomized control trial aims to test the hypothesis that twice-daily nurse-administered saline enema(SE) is comparable to physician-administrated SE in very low birth weight infants (VLBW) with meconium obstruction of prematurity (MOP). MOP is defined as no bowel opening for 48 h, and treatment failure is defined as the need for additional intervention and safety. Twice-daily SE was administered by accredited nurses, surgeons/neonatologists using standardized protocols. The outcomes were comparability of nurse to physician-administered SE in terms of frequency of administration, catheter insertion length and volume of enema, daily maximum meconium output, and treatment failure, defined as the need for additional intervention. Safety outcomes were evaluated. Twenty-eight infants were managed with SE. 389 SE were administered, 96 and 293 in 750-999g and 1000-1500g birth weight groups, respectively. Nurses administered 72.9% and 81.5% of SE in 750-999g and 1000-1500g birth weight groups, respectively. Physicians performed the rest of the SE. Daily meconium output was comparable in nurse and physician-administered SE in both groups. There were no treatment failures or adverse events in both SE group. SE administered by nurses was found to be comparable in terms of safety, efficacy, and frequency of administration to that of physician-administered SE.

At 2.3 megabases in length, the dystrophin gene is enormous: transcription of a single mRNA requires approximately 16 hours. Principally expressed in skeletal muscle, the dystrophin protein product protects the muscle sarcolemma against contraction-induced injury, and dystrophin deficiency results in the fatal muscle-wasting disease, Duchenne muscular dystrophy. This gene is thus of key clinical interest, and therapeutic strategies aimed at eliciting dystrophin restoration require quantitative analysis of its expression. Approaches for quantifying dystrophin at the protein level are well established, however study at the mRNA level warrants closer scrutiny: measured expression values differ in a sequence-dependent fashion, with significant consequences for data interpretation. In this manuscript we discuss these nuances of expression and present evidence to support a transcriptional model whereby the long transcription time is coupled to a short mature mRNA half-life, with dystrophin transcripts being predominantly nascent as consequence. We explore the effects of such a model on cellular transcriptional dynamics, and then discuss key implications for the study of dystrophin gene expression, focussing both on conventional (qPCR) and next-gen (RNAseq) approaches.

Land-cover classification that uses very-high-resolution (VHR) remote sensing images is a topic of considerable interest. Although many classification methods have been developed, there is still room for improvements in the accuracy and usability of classification systems. In this paper, a novel post-processing approach based on a dual-adaptive majority voting strategy (D-AMVS) is proposed for improving the performance of initial classification maps. D-AMVS defines a strategy for refining each label of a classified map that is obtained by different classification methods from the same original image and fusing the different refined classification maps to generate a final classification result. The proposed D-AMVS contains three main blocks. 1) An adaptive region is generated by extending gradually the region around a central pixel based on two predefined parameters (T1 and T2) in order to utilize the spatial feature of ground targets in a VHR image. 2) For each classified map, the label of the central pixel is refined according to the majority voting rule within the adaptive region. This is defined as adaptive majority voting (AMV). Each initial classified map is refined in this manner pixel by pixel. 3) Finally, the refined classified maps are used to generate a final classification map, and the label of the central pixel in the final classification map is determined by applying AMV again. Each entire classified map is scanned and refined pixel by pixel based on the proposed D-AMVS. The accuracies of the proposed D-AMVS approach are investigated through two remote sensing images with high spatial resolutions of 1.0 and 1.3 m, respectively. Compared with the classical majority voting method and a relatively new post-processing method called general post-classification framework, the proposed D-AMVS can achieve a land-cover classification map with less noise and higher classification accuracies.

Keywords: Chronic Obstructive Pulmonary Disease (COPD), Long Non-Coding RNAs (lncRNAs), Molecular Pathogenesis, Inflammation, Lung Cancer, Diagnostic Biomarkers

Lung cancer, including both non-small cell lung cancer and small cell lung cancer, remains the leading cause of cancer-related mortality worldwide representing 18% of the total cancer deaths in 2020. Many patients are identified already at an advanced stage with metastatic disease and have a worsening prognosis. Recent advances in the genetic understanding of lung cancer have opened new avenues for personalized treatments and targeted therapies. This review examines the latest discoveries in the genetics of lung cancer, discusses key biomarkers, and analyzes current clinical therapies based on this genetic information. It will conclude with a discussion of future prospects and potential research directions.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

Exosomes are small extracellular vesicles produced by almost all cell types in the human body and exosomal microRNAs (miRNAs) are small non-coding RNA molecules that are known to serve as important biomarkers for diseases such as cancer. Given that the upregulation of miR-106b is closely associated with several types of malignancies, the sensitive and accurate detection of miR-106b is important but difficult. In this study, a surface acoustic wave (SAW) biosensor was developed to detect miR-106b isolated from the cancer cells based on immunoaffinity separation technique using our unique paddle screw device. Our novel SAW biosensor could detect a miR-106b concentration as low as 0.024 pM in a linear range from 0.1 pM to 1.0 μM with a correlation coefficient of 0.9939. Additionally, we were able to successfully detect miR-106b in total RNA extracted from the exosomes isolated from the MCF-7 cancer cell line, a model system for human breast cancer, with performance comparable to commercial RT-qPCR methods. Therefore, the exosome isolation by paddle screw method and the miRNA detection using the SAW biosensor has the potential to be used in basic biological research and clinical diagnosis as an alternative to RT-qPCR.

Background: Methotrexate (MTX) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible anti-tumoral potential of them in breast cancer (BC) cells. We aimed to determine the effects of MTX, which is widely used in clinical practice, on cell viability, Hypoxia-inducible factor (HIF) -1α, HIF-2α and prolyl 4-hydroxylase-transmembrane (P4H-TM) in BC cells (MCF-7) and health breast cell (HTERT-HME1) treated with MTX. Methods: Human healthy breast cells (HTERT-HME1) and BC cells (MCF-7) treated with MTX for 24 h, 48h, and 72 h, the effects of MTX on cell viability. Results: The cell viability and with half-maximal inhibitory concentration (IC50) values of of MTX treatment in healthy breast cells were determined to be higher than in MCF-7 cells. MTX showed higher cytotoxicity against MCF-7 cells. MTX significantly reduced cell viability values in HTERT-HME1 and MCF-7 cells. HIF-1α, HIF-2α, and P4H-TM levels was significantly higher in the MCF-7 group than the other groups. Morever, there was a moderate significant correlation between HIF-1α and HIF-2α levels and between HIF-1α and P4H-TM. Conclusions: MTX will show a further decrease in cell viability in long-term treatments of 48 and 72 hours, it is predicted that short-term use may be more appropriate. P4H-TM may be a novel regulator of hypoxia in BC cells. HIF-1α, a key protein responsible for the molecular mechanism of hypoxia in cells, is a key mediator between P4H-TM and hypoxia in MTX-treated cells. HIF-1α, HIF-2α, and P4H-TM values may be markers that can be used as a panel to differentiate BC from healthy women.

The FAS ligand (FASLG) is expressed on lymphocytes, which employ it to activated death receptors on targets cells. Cancer cells are generally resistant to apoptosis triggered by FASLG. In this work we found a way to circumvent this resistance by treatment with actinomycin D (ActD) and nutlin-3a (Nut3a). We selected this drug combination based on our transcriptomic data showing strong activation of proapoptotic genes, including the ones for receptor mediated apoptosis, in cells exposed to actinomycin D and nutlin-3a. To test our hypothesis, we pre-exposed cancer cell lines to this drug combination for 45h and next we treated them with recombinant FASLG. This almost instantaneously killed most cells. Actinomycin D and nutlin-3a strongly synergized in the sensitization because the effect of the drugs acting solo was not as spectacular as the drug combination, which together with FASLG killed more than 99% of cells. Based on the caspase activation pattern (caspase-8, caspase-9, caspase-10), we conclude that both extrinsic and intrinsic pro-apoptotic pathways were engaged. In engineered p53-deficient cells this pro-apoptotic effect was completely lost. Therefore, the combination of ActD+Nut3a activates p53 in an extraordinary way, which overcomes the resistance of cancer cells to apoptosis triggered by FASLG. Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112 and actinomycin D + idasanutlin had similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD+Nut3a+FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.

Enzalutamide is a second-generation androgen-receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker after enzalutamide administration. A retrospective subgroup analysis and prognostic survey of 43 patients with mCRPC and bone metastases, treated in Juntendo University-affiliated hospitals from 2015–2022, were conducted. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months post-treatment. Relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with CTCs at baseline. Furthermore, patients showing negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positive continuation. Two biomarkers–higher hemoglobin at baseline and achieving negative-reversion of CTCs–were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in treatment of mCRPC.

Breast cancer (BC) ranks among the most prevalent cancers diagnosed in women. Its treatment necessitates precision tailored to the cancer's genetic makeup for enhanced efficacy. Research has been directed towards natural compounds for their anti-BC properties, aiming to augment existing treatment modalities. Chromolaena tacotana (Klatt) R.M. King and H. Rob, commonly referred to as Ch. tacotana, is a notable source of bioactive hydroxy-methylated flavonoids. However, the specific anti-BC mechanisms of these flavonoids, particularly those present in the plant's inflorescences, remain partly undefined. This study focuses on assessing a chalcone derivative extracted from Ch. tacotana inflorescences for its potential to concurrently activate regulated autophagy and intrinsic apoptosis in Luminal A and triple-negative BC cells. We determined the chemical composition of the chalcone using ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopy. Its selective cytotoxicity against BC cell lines was assessed using the MTT assay. Flow cytometry and western blot analysis were employed to examine the modulation of proteins governing autophagy and the intrinsic apoptosis pathway. Additionally, in silico simulations were conducted to predict interactions between the chalcone and various anti-apoptotic proteins, including the mTOR protein. The chalcone was identified as 2',4-dihydroxy-4',6'-dimethoxy-chalcone (DDC), also known as Flavokavain C (FKC). This compound demonstrated selective inhibition of BC cell proliferation and triggered autophagy and intrinsic apoptosis. It induced cell cycle arrest in the G0/G1 phase and altered mitochondrial outer membrane potential (∆ψm). The study observed the activation of autophagic LC3-II and mitochondrial pro-apoptotic proteins in both BC cell lines. The regulation of Bcl-XL and Bcl-2 proteins varied according to BC subtype, yet they showed promising molecular interactions with DDC. Among the examined pro-survival proteins, mTOR and Mcl-1 exhibited the most favorable binding energies and were downregulated in MCF-7 and MDA-MB-231 cell lines. Further research is needed to fully understand the molecular dynamics involved in the activation and interaction of autophagy and apoptosis pathways in cancer cells in response to potential anticancer agents like the hydroxy-methylated flavonoids from Ch. tacotana.

Ovarian cancer is the common cause of death among gynecological cancers. Although ovarian cancer initially responds to chemotherapy, the frequent recurrence in patients remains a therapeutic challenge. Pyruvate kinase M2 (PKM2) plays a pivotal role in regulating cancer cell survival. However, its therapeutic roles remain unclear. Here, we investigated the anticancer effects of compound 3K, a specific PKM2 inhibitor, on autophagic and apoptotic pathway regulation in SK-OV-3 (PKM2-overexpressing human ovarian adenocarcinoma cell line). The anticancer effect of compound 3K was examined using the MTT and colony formation assay in SK-OV-3. The results of tissue microarray showed that PKM2 expression positively correlated with the severity of the tumor. Moreover, the expression of pro-apoptotic proteins increased in SK-OV-3 following compound 3K treatment. Compound 3K induced AMPK activation, which was accompanied by the inhibition of mTOR. Additionally, this compound inhibited glycolysis, resulting in reduced proliferation in SK-OV-3. Compound 3K treatment suppressed tumor progression in vivo xenograft model. Our findings suggest that the inhibition of PKM2 by compound 3K affected Warburg effects and induced autophagic cell death. Therefore, the use of specific PKM2 inhibitors to block the glycolytic pathway and target cancer cell metabolism represents a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

The first member of the family, visual arrestin-1, was discovered in the late 1970s. Later the other three mammalian subtypes were identified and cloned. The first described function was regulation of GPCR signaling: arrestins bind active phosphorylated GPCRs, blocking their coupling to G proteins. It was later discovered that receptor-bound and free arrestins interact with numerous proteins, regulating GPCR trafficking and various signaling pathways, including those that determine cell fate. Arrestins have no enzymatic activity, they function by organizing multi-protein complexes and localizing their interaction partners to particular cellular compartments. Today we understand the molecular mechanism of arrestin interactions with GPCRs better than the mechanisms underlying other functions. However, even limited knowledge enabled the construction of signaling-biased arrestin mutants and extraction of biologically active monofunctional peptides from these multifunctional proteins. Manipulation of cellular signaling with arrestin-based tools has research and likely therapeutic potential: re-engineered proteins and their parts can produce effects that conventional small molecule drugs cannot.

This article summarizes the results of a research conducted to create an intelligent platform supporting small farmers growing vegetables. In Bulgaria, many farmers use relatively small areas for their production. Considering this situation, the platform is designed for regional use, trying to make maximum use of the specific climatic features of the monitored microdistrict. Consequently, special attention is paid to the possibilities of adapting the platform to the specific environment in which the observed plants grow. Thus, the platform is implemented as an agent-oriented system providing needed flexibility. The core of the platform is a personal assistant, which is responsible for tracking the vegetation cycle of the monitored crop and, upon detection of anomalies, preparing warnings to the farmer. The general architecture of the platform is also presented. In a distributed knowledge base, agriculture-specific knowledge are stored. Furthermore, a standardized interface for receiving data from the sensor networks located in the production areas is briefly described. Currently, the platform is being tested for monitoring four varieties of tomatoes grown on the territory of the national research center for potato breeding. Special attention is paid to the measurements carried out. Conclusions have been drawn that will help improve the platform.

If visible matter alone is present in the Universe, General Relativity (GR) and its Newtonian weak field limit cannot explain several pieces of evidence, from the largest to the smallest scales. The most investigated solution is the cosmological model ΛCDM, where GR is valid and two dark components are introduced, dark energy and dark matter, to explain the ∼70% and ∼25% of the mass-energy budget of the Universe, respectively. An alternative approach is provided by modified gravity theories, where a departure of the gravity law from ΛCDM is assumed and no dark components are included. This work presents refracted gravity (RG), a modified theory of gravity formulated in a classical way where the presence of DM is mimicked by a gravitational permittivity ϵ(ρ) monotonically increasing with the local mass density ρ, which causes the field lines to be refracted in small density environments. Specifically, the flatter the system the stronger the refraction effect and, thus, the larger the mass discrepancy if interpreted in Newtonian gravity. RG presented several encouraging results in modelling the dynamics of disk and elliptical galaxies and the temperature profiles of the hot X-ray emitting gas in galaxy clusters and a covariant extension of the theory seems to be promising.

Energy transition is one of the greatest challenges facing humanity today. All micro, small, medium and large enterprises in operation will have to face it, and some can al-ready boast the first successes in this regard. This paper focuses on the involvement of these smallest players in energy transition. Micro and small entities are the largest part of the economy, having a great influence on its development. Looking at the wide scale of their activities, these entities are distinguished by a specific owner-manager relationship. This means that the final decision-making is influenced by business goals, but also by the manager's approach, their awareness of changes, and personal and other factors. Based on a structured and standardized survey questionnaire, the research was carried out using the Computer-Assisted Telephone Interviewing technique between April and May 2022 among owners of micro and small enterprises operating in Poland. The survey showed that active engagement of micro and small enterprises in energy efficiency initiatives is related to their market success and financial health.

China is rich in coal resources, but the complex hydrogeological conditions lead to difficulties in coal mining, such as coal mine collapse, roof and water damage, and other accidents that occur frequently, resulting in many casualties and property losses. The use of coal mine hole detection technology to detect and analyze the internal environment of the coal mine in advance helps to reduce safety hazards and prevent coal mine accidents, for the existing coal mine hole detection technology operation is cumbersome, not easy to control, and insufficient depth of jacking prob-lems, this paper designs a new type of mine hole detection small robot. Firstly, this paper ana-lyzes the function and structural design of the mine hole detection robot, designs the variable diameter function according to the characteristics of narrow and uneven mine holes in coal mines, and analyzes the mechanics of the critical parts through theoretical calculations; secondly, based on the three-dimensional modeling software, established the structural model of the small robot for mine hole detection; after that, designed the robot's hardware circuits and control pro-grams for the presence of water and gas inside the mine hole, highlighting the need to carry out a new type of mine hole detection small robot. After that, we designed the robot's hardware circuit and control program, giving particular emphasis to the safety design of the circuit for the pres-ence of water and gas inside the mine hole of the coal mine. Finally, to verify the feasibility of the design program, the basic parameters and function tests of the mine hole detection small robot are carried out. The experimental results show that the mine hole inspection small robot realized by this design can adapt to the working hole diameter from 65 mm to 100 mm, the maximum working power is only 12 W, and the maximum crawling speed is 3.96 m/min. The maximum crawling slope reaches 90°, which can meet the actual mine hole inspection needs. The research can provide theoretical and design guidance for developing the mine hole detection robot with substantial engineering practical reference value.

Small-scale facilities play a significant role in the landscape of nuclear physics research in Europe. They address a wide range of fundamental questions and are essential for teaching and training personnel in accelerator technology and science, providing them with diverse skill sets, complementary to large projects. The current status and perspectives of nuclear physics research at small-scale facilities in Europe will be given.

The ever-growing repertoire of genomic techniques continues to expand our understanding of true diversity and richness of prokaryotic genomes. Riboproteogenomics laid the foundation for dynamic studies of previously overlooked genomic elements. Most strikingly, bacterial genomes were revealed to harbour robust repertoires of small open reading frames (sORFs) encoding a diverse and broadly expressed range of small proteins, or sORF-encoded polypeptides (SEPs). In recent years, continuous efforts led to great improvements in annotation and characterization of such proteins, yet many challenges remain to fully understand the pervasive nature of small proteins and their impact on bacterial biology. In this work we review recent developments in the dynamic field of bacterial genome reannotation, catalogue important biological roles carried out by small proteins and identify challenges obstructing the way to full understanding of these elusive proteins.

Abstract: Background: The birthrate of Black preterm (BPT) infant is 65% higher than White preterm (WPT) infants with BPT mortality 2.3 times higher. The incidence of culture positive sepsis is as high as 41% in preterms. This study aimed to examine infections and mortality in BPTs and WPTs. Methods: We enrolled 362 preterms born < 32 weeks gestational age (GA) between 2019-2023 in 5 neonatal intensive care unit (NICU)s to study onset of infections, and dispositions; RedCap data were analyzed for descriptive statistics. Results: 226 BPTs (63.5%) and 107 WPTs (30.8%) enrolled, with 29 other than White or Black, 50.5% female, mean GA of 27.67 weeks and 986.74 grams birthweight. Of 426 suspected infections evaluated in enrolled infants, there were 7 infants with early onset sepsis (EOS) and 39 infants with late onset sepsis (LOS). The incidence of EOS was 1.9% overall, 2.2% in BPTs vs 0.9% in WPTs. LOS incidence was 10.8% overall, 11.9% in BPTs and 9.3% in WPTs. Both BPT and WPT infants had ~ 8% gram-positive LOS events and 3% gram-negative LOS events; however, 82% of all gram-negative LOS episodes occurred in BPTs. There were 27 urinary tract infections and 78% were in BPTs. Two cerebral spinal fluid cultures were positive in BPTs. Necrotizing enterocolitis was diagnosed in 5.8% of the sample, with an incidence of 6.1% in BPTs versus 4.7% in WPTs. Death occurred in 6.0% of the enrolled infants with the rate of death being slightly higher in BPTs (7.0%) versus WPTs (5.6%). Conclusions: BPTs had a higher rate of positive cultures, double the gram-negative infections, a much higher rate of urinary tract infec-tions and a higher rate of mortality than their WPT counterparts. This study emphasizes higher risk of morbidity and mortality for BPTs.

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), which suggests a close association. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n=148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Se-rum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤ 16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β= -0.018, 95% CI -0.033 to -0.003, P=0.022) and 0.048 SD (standardized β= -0.048, 95% CI -0.083 to -0.014, P=0.006), respectively. Additionally, the high serum 25OHD groups (> 95.9 nmol/L) had 0.038 SD (standardized β= -0.038, 95% CI -0.072 to -0.004, P=0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusion: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.

Commercial buildings are a significant consumer of energy worldwide. Logistics facilities, and specifically warehouses, are a common building type yet under-researched in the demand-side energy forecasting literature. Warehouses have an idiosyncratic profile when compared to other commercial and industrial buildings with a significant reliance on a small number of energy systems. As such, warehouse owners and operators are increasingly entering in to energy performance contracts with energy service companies (ESCOs) to minimise environmental impact, reduce costs, and improve competitiveness. ESCOs and warehouse owners and operators require accurate forecasts of their energy consumption so that precautionary and mitigation measures can be taken. This paper explores the performance of three machine learning models (Support Vector Regression (SVR), Random Forest, and Extreme Gradient Boosting (XGBoost)), three deep learning models (Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), and Gated Recurrent Unit (GRU)), and a classical time series model, Autoregressive Integrated Moving Average (ARIMA) for predicting daily energy consumption. The dataset comprises 8,040 records generated over an 11-month period from January to November 2020 from a non-refrigerated logistics facility located in Ireland. The grid search method was used to identify the best configurations for each model. The proposed XGBoost models outperform other models for both very short load forecasting (VSTLF) and short term load forecasting (STLF); the ARIMA model performed the worst.

Preterm infants are at significant risk to develop reduced bone mineralization based on inadequate supply of calcium and phosphorus (Ca-P). Biochemical parameters can be used to evaluate the nutritional intake. The direct effect of nutritional intake on changes in biochemical parameters has not been studied. Our objective was to evaluate the effect of Ca-P supplementation on biochemical markers as serum (s)/urinary (u) Ca and P; alkaline phosphatase (ALP); tubular reabsorption of P (TrP) and urinary ratios for Ca/creatinin and P/creatinin in Very-Low-Birth-Weight infants on postnatal day 1, 3, 5, 7, 10, and 14. This observational study compared two groups with High (n = 30) and Low (n = 40) intake of Ca-P. Birth weight: median (IRQ) 948 (772-1225) vs. 939 (776-1163) grams; Gestational age: 28.2 (26.5-29.6) vs. 27.8 (26.1-29.4) weeks. Daily median concentrations of biochemical parameter were not different between the groups but linear regression mixed model analyses showed that Ca intake increased the uCa and TrP (p = 0.04) and decreased ALP (p = 0.00). Phosphorus intake increased sP, uP and uP/creat ratio and ALP (p ≤ 0.02) and caused decrease in TrP (p = 0.00). Protein intake decreased sP (p = 0.000), while low gestational age and male gender increased renal excretion of P (p < 0.03). Standardized repeated measurements showed that biochemical parameters were affected by nutritional intake, gestational age and gender.

The text examines the assessment of learning in science and the use of technologies like Scratch to enhance this process. Assessment is crucial for measuring progress and guiding teaching, especially in science where it fosters scientific skills and understanding. The study focuses on third-year secondary education students, evaluating the impact of Scratch on their learning compared to a gamification approach. Scratch, developed by MIT, is effective in interactive teaching and improves academic performance and student motivation. The research used an experimental design with a control group (gamification) and an experimental group (Scratch), measuring acquired knowledge through pretests and posttests. Results show that both groups significantly improved their knowledge, although the control group had a higher baseline initially. Students valued collaboration and playful learning. However, they faced technical challenges and highlighted the importance of teamwork. The study concludes that Scratch has great educational potential, suggesting improvements such as redesigning activities and increasing work sessions to maximize its effectiveness in learning and student motivation.

Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Phar-maceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with associated drug trends and characteristics. Our findings indicate that similar to　Parkinson’s disease, age-related differences affect the onset of these events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, side effects can vary depending on the site of action. These insights underline the importance of swift identification of the drugs suspected of causing these events and implementation of measures to reduce their side effects.

A human eye has about 120 million rod cells and 6 million cone cells. This huge number of light sensing cells inside a human eye will continuously produce a huge quantity of visual signals which flow into a human brain for daily processing. However, the real-time processing of these visual signals does not cause any fatigue to a human brain. This fact tells us the truth which is to say that human-like vision processes do not rely on complicated formulas to compute depth, displacement, and colors, etc. On the other hand, a human eye is like a PTZ camera. Here, PTZ stands for pan, tilt and zoom. We all know that in computer vision, each set of PTZ parameters (i.e., coefficients of pan, tilt and zoom) requires a dedicated calibration to determine a camera’s projection matrix. Since there is an infinite number of PTZ parameters which could be produced by a human eye, it is unlikely that a human brain stores an infinite number of calibration matrices for each human eye. Therefore, it is an interesting question for us to answer, which is to say whether simpler formulas of computing depth and displacement exist or not. Moreover, these formulas must be calibration friendly (i.e., easy process on the fly or on the go). In this paper, we disclose an important discovery of a new solution to 3D projection in a human-like binocular vision system. The purpose of doing 3D projection in binocular vision is to undertake forward and inverse transformations (or mappings) between coordinates in 2D digital images and coordinates in a 3D analogue scene. The formulas underlying the new solution are accurate, easily computable, easily tunable (i.e., to be calibrated on the fly or on the go) and could be easily implemented by a neural system (i.e., a network of neurons). Experimental results have validated the discovered formulas.

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.

Cardiac hypertrophy typically follows myocardial damage, a process known to involve members of the Krüppel-Like Factors (KLFs) which have pro-hypertrophic and anti-hypertrophic roles. Our study delved into the molecular mechanisms underlying KLFs-cardiac hypertrophy interplay post myocardial infraction. We induced myocardial dam-age in rats using isoproterenol. Total RNA was extracted from the left ventricle and Quantitative Real Time RT-PCR was conducted to assess the expression of KLFs, cardiac commitment genes, inflammatory markers, and certain conduction-related genes. We devel-oped a computational approach to construct a proteomic network centered on KLFs. Initial results revealed early expression (2-3 days post-induction) of KLF3, KLF4 and KLF6, followed by the subsequent expression of KLF11 and KLF15 (5-8 days after induction). In the maturation stage, KLF12 and KLF13 regulators were found upregulated. IL-6 was gradually found to be upregulated through. Interaction analysis revealed KLF3, KLF8 and KLF12 interacted with cardiac electrical functions. RT-PCR confirmed up-regulation in cardiac genes linked to electrical function and scar maturation. Our findings underscore the central role of KLFs during the modulation of the cardiac hypertrophic response. Dysregulation of KLF expression resulted in damaged myocardium, participating in the progression of abnormal hypertrophy, highlighting their potential as therapeutic targets for heart diseases.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Methodologies for the synthesis and purification of metabolites, which have been developed following their discovery, analysis and structural identification, have been involved in numerous life science milestones. The renewed focus on the small molecule domain of biological cells has also created an increasing awareness of the rising gap between the metabolites identified and the metabolites which have been prepared as pure compounds. Due to the large number and molecular diversity of metabolites the design and engineering of resource-efficient and straightforward synthetic methodologies for their production have attracted much interest. The variety of metabolic pathways in biological cells provide a wonderful blueprint for designing simplified and resource-efficient synthetic routes to desired metabolites. Therefore, biocatalytic systems have become key enabling tools for the synthesis of an increasing number of metabolites, which can then be utilized as standards, enzyme substrates, inhibitors or products, or for the discovery of novel biological functions.

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.

Visual signals are the upmost important source for robots, vehicles or machines to achieve human-like intelligence. Human beings heavily depend on binocular vision to understand the dynamically changing world. Similarly, intelligent robots or machines must also have the innate capabilities of perceiving knowledge from visual signals. Until today, one of the biggest challenges faced by intelligent robots or machines is the matching in stereovision. In this paper, we present the details of a new principle toward achieving a robust matching solution which leverages on the use and integration of top-down image sampling strategy, hybrid feature extraction, and RCE neural network for incremental learning (i.e., cognition) as well as robust match-maker (i.e., recognition). A preliminary version of the proposed solution has been implemented and tested with data from Maritime RobotX Challenge (www.robotx.org). The contribution of this paper is to attract more research interest and effort toward this new direction which may eventually lead to the development of robust solutions expected by future stereovision systems in intelligent robots, vehicles and machines.

Spacetime torsion is known to be highly suppressed at the end of inflation, called preheating. Of course this fact does not avoid that metric could affect the cosmic dynamos at preheating phase as was showed by Bassett et al, in the general relativity (GR) case. In this paper, is to show that a torsionful magnetogenesis in QED effective lagrangean, drives either a torsion damping or an amplification mechanism or dynamo effect, depending upon torsion chirality. The present extension of Basset et al theory yields a new magnetic field expression $B\sim{a^{(1\pm{\beta})}}$, obtained from dynamo equation in QED. Here a cosmic factor ${\beta}=g_{T}{\eta}k$ is present. In a second example we find Higgs inlationary fields in Einstein-Cartan gravity thick domain walls (DWs). Recently a moodified Einstein-Cartan gravity was given by M Shaposhnikov et al [PRL (2020)] to obtain higgs like inflatons as a portal to dark energy.

The viral genus Henipavirus includes two highly virulent zoonotic viruses of serious public health concern. Hendra henipavirus and Nipah henipavirus outbreaks are restricted to Australia and Southeast Asia, respectively. Henipavirus genus comprises mostly bat-borne viruses, but exceptions have already been described with novel viruses having rodents and shrews as reservoir animals. In the Americas, scarce evidence supports the circulation of these viruses. In this communication, we report a novel henipa-like virus from opossums (Marmosa demerarae) from a forest fragment area at Peixe-Boi municipality, Brazil, after which the virus was named the Peixe-Boi virus (PBV). The application of next-generation sequencing and metagenomic approach led us to discover the original evidence of a henipa-like virus genome in Brazil and South America and the original description of henipaviruses in marsupial species. These findings emphasize the importance of further studies to characterize PBV and clarify its ecology, impact on public health and its relationship with didelphid marsupials and other henipaviruses.

Salmonella enterica serovar Newport bacteriophage 7-11 shares 41 homologous ORFs with Escherichia coli phage phiEco32 and both phages encode a protein similar to bacterial RNA polymerase promoter specificity  subunit. Here, we investigated the temporal pattern of 7-11 gene expression during the infection and compared it to the previously determined transcription strategy of phiEco32. Using primer extension and in vitro transcription assays we identified eight promoters recognized by host RNA polymerase holoenzyme containing 7-11  subunit SaPh711_gp47. These promoters are characterized by a bipartite consensus GTAAtg-(16)-aCTA and are located upstream of late phage genes. While dissimilar from single-element middle and late promoters of phiEco32 recognized by holoenzyme formed by the phi32_gp36  factor, the 7-11 late promoters are located at genome positions similar to those of phiEco32 middle and late promoters. Two early 7-11 promoters are recognized by RNA polymerase holoenzyme containing host primary σ70 factor. Unlike the case of phiEco32, no shut off of σ70-dependent transcription is observed during 7-11 infection and there are no middle promoters. These differences can be explained by the fact that phage 7-11 does not encode a homologue of phi32_gp79, an inhibitor of host and early phage transcription and an activator of transcription by the phi32_gp36-holoenzyme.

The measurements of the proton electromagnetic form factors in the time-like region using the initial state radiation technique are reviewed. Recent experimental studies have shown that initial state radiation processes at high luminosity electron-positron colliders can be effectively used to probe the electromagnetic structure of hadrons. The BABAR experiment at the B-factory PEP-II in Stanford and the BESIII experiment at the $\tau$-charm factory BEPC-II in Beijing have measured the time-like form factors of the proton using the initial state radiation process $e^{+}e^{-}\to pbar{p}\gamma$. The two kinematical regions where the photon is emitted from the initial state at small and large polar angles have been investigated. In the first case the photon is in the region not covered by the detector acceptance and is not detected. The Born cross section and the proton effective form factor have been measured over a wide and continuous range of the the momentum transfer squared $q^2$ from threshold up to ~42 (GeV/c)$^2$. The ratio of electric and magnetic form factors of the proton has been also determined. In this report, the theoretical aspect and the experimental studies of the initial state radiation process $e^{+}e^{-}\to p\bar{p}\gamma$ are described. The measurements of the Born cross section and the proton form factors obtained in these analyses near the threshold region and in the relatively large $q^2$ region are examined. The experimental results are compared to the predictions from theory and models. Their impact on our understanding of the nucleon structure is discussed.

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.

This is a short introductory review on quantum-like modeling of cognition with applications to decision making and rationality. The aim of the review is twofold: a) to present briefly the apparatus of quantum information and probability theory useful for such modeling; b) to motivate applications of this apparatus in cognitive studies and artifical intelligence, psychology, decision making, social and political sciences. We define quantum rationality as decision making that is based on quantum information processing. Quantumly and classically rational agents behaves differently. A quantum-like agent can violate the Savage Sure Thing Principle, the Aumann theorem on impossibility of agreeing to disagree.Such an agent violates the basic laws of classical probability, e.g., the law of total probability and the Bayesian probability inference. In some contexts, ``irrational behavior'' (from the viewpoint of classical theory of rationality) can be profitable, especially for agents who are overloaded by a variety of information flows. Quantumly rational agents can save a lot of information processing resources. At the same time, this sort of rationality is the basis for quantum-like socio-political engineering, e.g., social laser. This rationality plays the important role in the process of decision making not only by biosystems, but even by AI-systems. The latter equipped with quantum(-like) information processors would behave irrationally, from the classical viewpoint. As for biosystems, quantum rational behavior of AI-systems has its advantages and disadvantages. Finally, we point out that quantum-like information processing in AI-systems can be based on classical physical devices, e.g., classical digital or analog computers.

One method of creating a brass coating is through electrodeposition, which is most often completed in cyanide galvanic baths. Because of the toxicity of cyanides, many are working on the development of cyanide-free baths, which are promising but not satisfactory to replace the classic methods. The purpose of the study was to explore a new generation of non-aqueous cyanide-free baths based on 1-ethyl-3-methylimidazolium acetate ionic liquids. The study involved the formation of copper, zinc, and brass coatings. The influence of the bath composition, cathodic current density, and temperature was determined. The obtained coatings were characterized by their morphology, chemical composition, roughness, and corrosion resistance. It was found that the structure of the obtained coatings is strongly dependent on the process parameters. The three main structures observed were fine-grained, porous, and olive-like. To the best knowledge of the authors, it is the first time the olive-like structure was observed in the case of an electrodeposited coating. The Cu-Zn coatings consisted of 19–96 at.% copper and exhibited relatively strong corrosion resistance. High improvement of corrosion properties was found in the case of copper and brass coatings with an olive-like structure.

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

Quantum coherence is an important physical resource in quantum information science, and also as one of the most fundamental and striking features in quantum physics. In this paper, we obtain a symmetry-like relation of relative entropy measure $C_r(\rho)$ of coherence for $n$-partite quantum states $\rho$, which gives lower and upper bounds for $C_r(\rho)$. Meanwhile, we discuss the conjecture about the validity of the inequality $C_r(\rho)\leq C_{\ell_1}(\rho)$ for any state $\rho$. We observe that every mixture $\eta$ of a state $\rho$ satisfying $C_r(\rho)\leq C_{\ell_1}(\rho)$ and any incoherent state $\sigma$ also satisfies the conjecture. We also note that if the von Neumann entropy is defined by the natural logarithm $\ln$ instead of $\log_2$, then the reduced relative entropy measure of coherence $\bar{C}_r(\rho)=-\rho_{\rm{diag}}\ln \rho_{\rm{diag}}+\rho\ln \rho$ satisfies the inequality ${\bar{C}}_r(\rho)\leq C_{\ell_1}(\rho)$ for any mixed state $\rho$.

Several optimization models of irreversible reverse cycle machines have been developed based on different optimization criteria in the literature, most of them using linear heat transfer laws at the source and sink. This raises the issue how close to actual operation conditions they are, since the heat transfer law on the phase-change processes is dependent on ΔT3. This paper addresses this issue by proposing a general model for study and optimization of thermal machines with two heat reservoirs applied to a Carnot-like refrigerator, with non-linear heat transfer laws and internal and external irreversibility. The optimization was performed using First and Second Law of Thermodynamics and Lagrange multipliers method. Thus, several constraints were imposed to the system, also different objective functions were considered, allowing finding the optimum operating conditions, as well as the limited variation ranges of the system parameters. Results show that the nature of the heat transfer laws affects the optimum values of system parameters for obtaining maximum performances and also their magnitude. Sensitivity studies with respect to system several parameters are presented. The results contribute to the understanding of the system limits in operation under different constraints and allow choosing the most convenient variables in given circumstances.

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

Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs' ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation uses blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte Antigen 4 and anti-programmed Death-1 antibodies has shown promise by enhancing T cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs' efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T cell receptors could further augment the anti-tumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.

Kisspeptin, a key neuropeptide derived from the KISS1 gene, is renowned for its critical role in regulating the hypothalamic-pituitary-gonadal axis and reproductive hormone secretion. Beyond its primary function in reproductive biology, emerging research has illuminated its influence in various cancers, mediating significant effects through its interaction with the G-protein coupled receptor, Kisspeptin receptor. This interaction has been implicated in modulating cellular pro-cesses such as proliferation and metastasis, making it a potential target for therapeutic interven-tion. Our study initially screened ten kisspeptin-10 analogs through cytotoxic effects of kisspep-tin-10 (KP10) and its analogs in several cancer types, including cervical, prostate, breast, and gastric cancers, with a particular focus on cervical cancer where the most profound effects were observed. Further exploration using kinase array assays revealed that these analogs specifically alter key kinases involved in cancer progression. Migration assays demonstrated a substantial decrease in cell motility, and Bioluminiscence Resonance Energy Transfer assays confirmed these analogs strong interactions with the kisspeptin receptor. Overall, our results indicate that these KP10 analogs not only hinder cervical cancer cell proliferation but also curtail migration through targeted modulation of kinase signaling, suggesting their potential as therapeutic ayfgents in managing cervical cancer progression. This comprehensive approach underscores the therapeutic promise of exploiting kisspeptin signaling in cancer treatment strategies.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Pancreatic ductal adenocarcinoma (PDAC) represents an extremely aggressive type of cancer due in part to early invasion and metastasis, which in turn involves epithelial-mesenchymal transition (EMT) of the tumor cells. Prompted by the discovery that two PDAC-derived tumor cell lines of the quasi-mesenchymal subtype (PANC-1, MIA PaCa-2) exhibit neuroendocrine differentiation (NED), we asked whether NED is associated with EMT. Using quantitative real-time PCR and immunoblot analysis, we initially verified endogenous expression of various NED markers, i.e., chromogranin A (CHGA), synaptophysin (SYP), somatostatin receptor 2 (SSTR2) and SSTR5 in PANC-1 and MIA PaCa-2 cells. In HPDE6c7 normal pancreatic duct epithelial cells and in BxPC-3, another PDAC cell line with an epithelial phenotype, the expression of CHGA, SYP and neuron-specific enolase 2 (NSE) was either undetectable or much lower than in PANC-1 and MIA PaCa-2 cells. Parental cultures of PANC-1 cells exhibit EM plasticity (EMP) and harbor clonal subpopulations with different EMT phenotypes [Ungefroren et al 2022]. Monitoring the NED state of mesenchymal and epithelial PANC-1 subclones showed that the NE phenotype is more pronounced in M-type clones when compared to E-type ones. Inducing EMT in parental cultures of PANC-1 cells by treatment with transforming growth factor (TGF)-β1 repressed epithelial genes and co-induced mesenchymal and NED genes, except for SSTR5. Surprisingly, treatment with bone morphogenetic protein (BMP)-7 differentially affected gene expression in PANC-1 and MIA PaCa-2 cells. It synergised with TGF-β1 in the induction of vimentin, SNAIL, SSTR2 and NSE but antagonised it in the regulation of CHGA and SSTR5. From these data, we conclude that in EMT of PDAC cells mesenchymal and NED markers are co-regulated, and that mesenchymal-epithelial transition (MET) is associated with a loss of both the mesenchymal and NED phenotypes. Analysing NED in another tumor type, small cell carcinoma of the ovary hypercalcemic type (SCCOHT), revealed that two model cell lines of this disease (SCCOHT-1, BIN-67) do express CDH1, SNAI1, VIM, CHGA, SYP, ENO2 and SSTR2, but that in contrast to BMP-7 none of these genes was transcriptionally regulated by TGF-β1. We conclude that in PDAC-derived tumor cells, NED is closely linked to EMT and TGF-β signaling, which may have implications for the therapeutic use of TGF-β inhibitors in PDAC management.

Abstract: In this paper we describe how the administration of drone brood homoge-nate (DBH) influenced intestinal secretion of IgA, MUC-2, morphometric parameters, peripheral blood values, and expression of cytokines. A total of 12 pigs were divided into three groups, two experimental, first fed with 100 mg DBH.kg-1 (E1), second with 200 mg DBH.kg-1 (E2) of body weight, and a control (C) group without DBH in the di-et. Animals didn't show significant changes in average weight gains and feed conver-sion among evaluated groups. Feeding a diet containing 200 mg DBH.kg-1 of body weight in the E2 group produced an increase (p < 0.05) in the red cell distribution width, the percentage of metabolic activity of blood phagocytes in the peripheral blood, as well as splenic cell subpopulations CD4+ and CD21+. The villi height and their cutting surface were increased in the E2 group (p < 0.01), together with a gradual decrease in the concentration of MUC-2 and sIgA (p < 0.001). Upregulation of IL-8 (p < 0.0001), IL-10 (p < 0.05), and IL-18 (p < 0.001) was found mainly in E2 group. Results suggest, that supplementation of DBH in the feed of pigs formed optimal intestinal homeostasis.drone

Angiogenesis is a complex process that involves interactions between endothelial cells and various other cell types as well as the tissue microenvironment. Several previous studies have demonstrated that mast cells accumulate at angiogenic sites. In spite of the evidence suggesting a relationship between mast cells and angiogenesis, the association of mast cells and endothelial cells remains poorly understood. The present study aims to investigate the relationship between mast cells and endothelial cells during in vitro angiogenesis. When endothelial cells were co-cultured with mast cells, angiogenesis was stimulated. Furthermore, there was direct intercellular communication via gap junctions between the two cell types. In addition, the presence of mast cells stimulated endothelial cells to release angiogenic factors. Moreover, conditioned medium from the co-cultures also stimulated in vitro angiogenesis. The results from this investigation demonstrate that mast cells have both direct and indirect proangiogenic effects and provide new insights into the role of mast cells in angiogenesis.

Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the (1,6)fucose residue to the pentasaccharide core of complex N-glycans. Specifically, in the cellular model of colorectal cancer (CRC) progression formed using the human syngeneic lines SW480 and SW620, knockdown of the FucT-8-encoding FUT8 gene significantly enhanced TRAIL-induced apoptosis in SW480 cells. However, FUT8 repression did not affect SW620 cells, which suggests that core fucosylation differentiates TRAIL-sensitive premetastatic SW480 cells from TRAIL-resistant metastatic SW620 cells. In this regard, we provide evidence that phosphorylation of ERK1/2 kinases can dynamically regulate TRAIL-dependent apoptosis and that core fucosylation can control the ERK/MAPK pro-survival pathway in which SW480 and SW620 cells participate. Moreover, the depletion of core fucosylation sensitises primary tumour SW480 cells to the combination of TRAIL and low doses of 5-FU, oxaliplatin, irinotecan or mitomycin C. In contrast, combination of TRAIL and oxaliplatin, irinotecan or bevacizumab reinforces resistance of FUT8-knockdown metastatic SW620 cells to apoptosis. Consequently, FucT-8 could be a plausible target for increasing apoptosis and drug response in early CRC.

In this research, assume a SuperHyperGraph. Then a ``Failed SuperHyperClique'' $\mathcal{C}(NSHG)$ for a neutrosophic SuperHyperGraph $NSHG:(V,E)$ is the maximum cardinality of a SuperHyperSet $S$ of SuperHyperVertices such that there's a SuperHyperVertex to have a SuperHyperEdge in common. Assume a SuperHyperGraph. Then an ``$\delta-$Failed SuperHyperClique'' is a \underline{maximal} Failed SuperHyperClique of SuperHyperVertices with \underline{maximum} cardinality such that either of the following expressions hold for the (neutrosophic) cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)| > |S\cap (V\setminus N(s))|+\delta,~|S\cap N(s)| < |S\cap (V\setminus N(s))|+\delta.$ The first Expression, holds if $S$ is an ``$\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is an ``$\delta-$SuperHyperDefensive''; a``neutrosophic $\delta-$Failed SuperHyperClique'' is a \underline{maximal} neutrosophic Failed SuperHyperClique of SuperHyperVertices with \underline{maximum} neutrosophic cardinality such that either of the following expressions hold for the neutrosophic cardinalities of SuperHyperNeighbors of $s\in S:$ $~|S\cap N(s)|_{neutrosophic} > |S\cap (V\setminus N(s))|_{neutrosophic}+\delta,~ |S\cap N(s)|_{neutrosophic} < |S\cap (V\setminus N(s))|_{neutrosophic}+\delta.$ The first Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperOffensive''. And the second Expression, holds if $S$ is a ``neutrosophic $\delta-$SuperHyperDefensive''. A basic familiarity with Neutrosophic Failed SuperHyperClique theory, SuperHyperGraphs theory, and Neutrosophic SuperHyperGraphs theory are proposed.

Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart in previous studies and, therefore, its anti-cancer efficacy is investigated herein. This study focuses on the suppressive effect of FER on colon cancer, as the efficacious effect of curcumin on this typical cancer type has been well evidenced. In addition, demethoxy-feruloylacetone (DFER) was applied to compare the effect that might be brought on by the structural differences of the methoxy group. It was revealed that both FER and DFER inhibited the proliferation of HCT116 cells, possibly via suppression of the phosphorylated mTOR/STAT3 pathway. Notably, FER could significantly repress both the STAT3 phosphorylation and protein levels. Furthermore, both samples showed the capability of arresting HCT116 cells at the G2/M phase via the activation of p53/p21 and upregulation of cyclin-B. In addition, ROS elevation and changes in mitochondrial membrane potential were revealed, as indicated by p-atm elevation. The apoptotic rate rised to 36.9% and 32.2% after being treated by FER and DFER, respectively. In summary, both compounds exhibited an anti-cancer effect, and FER showed a greater pro-apoptotic effect, possibly due to the presence of the methoxy group on the aromatic ring.

PDEF is expressed in luminal epithelial cells of the prostate gland and associates with luminal phenotype. Hippo pathway regulates cell growth/proliferation, cellular homeostasis, and organ development by modulating phosphorylation of its downstream effectors. In previous studies, we observed decreased levels of PDEF during prostate cancer progression. In the present studies, we evaluated the effects of PDEF on total and phospho (Ser-127)YAP1 protein(a downstream effector of the Hippo pathway) levels in PC3 cells, a line of castrate resistant prostate cancer. We observed that the expression of PDEF in PC3 cells resulted in increased increased phospho(Ser127) -YAP1 protein levels. Our immunofluorescence analysis for YAP1 revealed an increased cytoplasmic/nuclear ratio of YAP1 in PDEF-PC3 cells as compared to VC-PC3 cells, suggesting PDEF may play a critical role in modulating YAP1 phosphorylation, and by extension in the regulation of the Hippo pathway. We also observed a decrease in YAP1 protein levels in prostate cancer tissues as compared to normal prostate tissues. Our analysis of multiple publicly available clinical cohorts revealed a gradual decrease in YAP1 mRNA expression during prostate cancer progression and metastasis. This decrease was similar to the decrease in PDEF levels which we reported earlier. In addition we observed further decreased in PDEF and YAP1 expression in Neuro-Endocrine Prostate Cancer (NEPC), and a direct correlation between PDEF and YAP1 expression. To the best of our knowledge, these results provide the first demonstration of modulation of YAP1 by PDEF in any system and suggest a cross-talk between PDEF and the Hippo pathway.

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

Background: Hashimoto’s thyroiditis (HT) is an autoimmune disease that progressively leads to thyroid gland destruction and hypothyroidism. Patients produce antibodies against two thyroid-specific antigens: thyroglobulin and thyroid peroxidase. As a result of the abnormal amount of thyroid hormone produced and its autoimmune etiology, patients with HT display a higher frequency of either autoimmune or non-autoimmune dermatological disorders. On ultrasound examination, HT can be detected by observing an enlarged thyroid gland with hypoechoic parenchymal regions or by observing a small gland indicating atrophy and diffusely heterogeneous parenchyma. Changes in the parenchymal vascularity can be observed as decreased or increased levels of vascularization. Objective: This study aimed to analyze the role of clinical data and ultrasound evaluation of patients with HT in suggesting an association with dermatological disorders. Patients and methods: Complete dermatological and endocrinological assessments as well as ultrasonography of the thyroid and lymphnodes were performed in HT patients. Results: The data obtained showed that a family history of thyroid disease, increased diameter of the inferior thyroid artery, and the presence of cervical lymphadenopathy were more frequent in the group of patients with dermatological diseases. Taken together, our results suggest the usefulness of ultrasound in determining a possible association between HT and dermatological disorders.

The swelling behavior of titanium-modified austenitic stainless steel 15-15Ti was investigated by pre-implantation of He at room temperature followed by Ni irradiation at 580 °C to peak doses of 120, 240 and 400 dpa. Relatively smaller cavities were observed in the zone of helium implantation while large cavities appeared in the region near the damage peak. A correction formula of the dpa curve was proposed and applied for samples with large swelling. It is found that the steady-state swelling rate of 15-15Ti keeps at ~1% /dpa even to high doses. By comparing the swelling data of the helium-implanted and helium-free regions at same doses, 70 dpa and 122 dpa, the suppression of excessive helium on swelling can be deduced at such doses.

Cardiovascular morbidities are the main cause of mortality in pituitary disorders accruing either from hormonal excess or deficiency. Cushing disease is associated with various cardiovascular abnormalities;visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia and hypercoagulability, structural and functional changes in heart, which do not seem to reverse completely even after remission. Acromegaly is related with insulin resistance, but also with structural and functional heart changes which consist acromegalic cardiomyopathy. Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism and endothelial dysfunction. On the other hand, hypopituitarism and conventional hormonal replacement which is far from ideal contribute to an unhealthy metabolic status which leads to atherosclerosis and premature mortality. This review aims to update literature on cardiovascular risk and relevant morbidities in pituitary disorders.

Severe combined immunodeficiency disorders (SCID) are a genetically heterogeneous group of inherited defects characterized by severe abnormalities of immune system development and function that lead to a wide spectrum in clinical manifestations. A subgroup of patients presents a disabling and life-threatening clinical course. In these cases, allogeneic hematopoietic stem cell transplant provides a curative approach. The occurrence of SCID-associated lymphoproliferative disorders is rare and occur mostly in adenosine deaminase-deficient severe combined immunodeficiency disorders, after allogeneic hematopoietic stem cell transplant. Epstein Barr virus infection is present in the majority of individuals with primary immunodeficiency developing lymphoma, revealing compromised anti-tumour surveillance of virally transformed cells. Herein, we report a rare case of diffuse large B cell lymphoma occurring in an Epstein Barr virus negative, non-transplanted X-linked severe combined immunodeficiency 4-months-old infant, successfully treated with immunotherapy and allogeneic stem cell transplantation. This case suggests that Epstein Barr virus -independent mechanism of neoplastic transformation must take action in severe combined immunodeficiency associated lymphoma and unveils the curative potential of donor T cells after allogeneic transplantation.

The vulnerability of alpine environments to climate change presses an urgent need to accurately model and understand these ecosystems. Popularity in use of digital elevation models (DEMs) to derive proxy environmental variables has increased over the past decade, particularly as DEMs are relatively cheaply acquired at very high resolutions (VHR; <1m spatial resolution). Here, we implement a multiscale framework and compare DEM-derived variables produced by Light Detection and Ranging (LiDAR) and stereo-photogrammetry (PHOTO) methods, with the aims of assessing their relevance and utility in species distribution modelling (SDM). Using a case study on the arctic-alpine plant Arabis alpina in two valleys in the western Swiss Alps, we show that both LiDAR and PHOTO technologies can be relevant for producing DEM-derived variables for use in SDMs. We demonstrate that PHOTO DEMs rivalled the accuracy of LiDAR, putting the current paradigm of LiDAR being the more accurate of the two methods into question. We obtained DEMs at spatial resolutions of 6.25cm-8m for PHOTO and 50cm-32m for LiDAR, where we determined that the optimal spatial resolutions of DEM-derived variables in SDM were between 1 and 32m, depending on the variable and site characteristics. We found that the reduced extent of PHOTO DEMs altered the calculations of all derived variables, which had particular consequences on their relevance at the site with heterogenous terrain. However, for the homogenous site, we found that SDMs based on PHOTO-derived variables generally had higher predictive powers than those derived from LiDAR at matching resolutions. From our results, we recommend carefully considering the required DEM extent to produce relevant derived variables. We also advocate implementing a multiscale framework to appropriately assess the ecological relevance of derived variables, where we caution against the use of VHR-DEMs finer than 50cm in such studies.

Aerial image classification has become popular and has attracted extensive research efforts in recent decades. The main challenge lies in its very high spatial resolution but relatively insufficient spectral information. To this end, spatial-spectral feature extraction is a popular strategy for classification. However, parameter determination for that feature extraction is usually time-consuming and depends excessively on experience. In this paper, an automatic spatial feature extraction approach based on image raster and segmental vector data cross-analysis is proposed for the classification of very high spatial resolution (VHSR) aerial imagery. First, multi-resolution segmentation is used to generate strongly homogeneous image objects and extract corresponding vectors. Then, to automatically explore the region of a ground target, two rules, which are derived from Tobler’s First Law of Geography (TFL) and a topological relationship of vector data, are integrated to constrain the extension of a region around a central object. Third, the shape and size of the extended region are described. A final classification map is achieved through a supervised classifier using shape, size, and spectral features. Experiments on three real aerial images of VHSR (0.1 to 0.32 m) are done to evaluate effectiveness and robustness of the proposed approach. Comparisons to state-of-the-art methods demonstrate the superiority of the proposed method in VHSR image classification.

The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness of, resistance to, and inappropriate use of antibiotics (ABs). The terms “drug ineffective,” “therapeutic failure,” “drug resistance,” “pathogen resistance,” and “multidrug resistance” were found in PV databases and dictionnaires, and denote ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. “Medication errors,” especially those related to dose and indication, are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce.

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of ASCs secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

We investigated the micro-threaded stem taper surface and the impact on premature failures, aseptic loosening, and infection. We have focused on the fretting, and crevice corrosion of micro-threaded tapers, as well as the characterization of microstructure and surface properties of two new and three retrieved Zweymüller stem tapers of cementless hip endoprostheses selected from a set of 45 stems. The retrievals examined were those in which the sole source of modularity with a metallic component was the head-stem taper interface between the Ti alloy taper stem and the ceramic head. To determine the surface chemistry and microstructures of both new and retrieved hip endoprostheses stem taper titanium alloy, scanning electron microscopy (SEM) was employed for morphological and microstructural analyses. At the same time, energy dispersive spectroscopy (EDS) was utilized for characterizing chemical element distribution, and electron backscattered diffraction (EBSD) was used for phase analysis. The micro-threated stem taper’s roughness for different manufacturers was investigated using an optical profilometer. Standard roughness pa-rameters Ra (average surface roughness) and Rz (mean peak to valley height of the roughness pro-file) were used in this investigation.Additionally, profile depth and peak spacing for different samples were investigated. The surface roughness results indicate no significant difference in roughness associated with varying survivorship times, ranging from 3 to 239 months, and across different manufacturers. Electrochemical studies revealed no fretting corrosion in retrieved stem tapers (ceramic head) that prematurely failed due to aseptic loosening after 239 months, infection after 3 months, and low-grade infection after a 32-month lifetime. Therefore, three retrieved ta-pers and two new ones for comparison underwent potentiodynamic measurements in Hank’s so-lution to ascertain the corrosion rate of new and retrieved stem taper surfaces. The results show a low corrosion rate for both new and retrieved samples that failed prematurely due to aseptic loosening. However, the corrosion rate of infected and low-grade infected tapers was higher. In conclusion, our study aligns with existing literature, suggesting that the use of ceramic heads de-creases the problem of taper corrosion and subsequently reduces premature failures in total hip arthroplasty.

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.

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.

THz radiation has assumed a great importance thanks to the efforts in the development of technological tools used in this versatile band of the electromagnetic spectrum. Here we propose a reflecting bi-mirror axicon-like device with wavelength-independent long focusing performances in the THz band, by exploiting the high thermo-mechanical deformation of the elastomer polydimethylsiloxane (PDMS). This deformation permits to achieve significant optical path modulations in the THz band and effective focusing. The surface of a PDMS layer is covered with a gold thin film, acting as heater thanks to its absorption for wavelengths below ~500 nm . An invariance property of the Fresnel integral has been exploited to verify experimentally the THz performances of the device with an ordinary visible laser source, finding excellent agreement with the theoretical predictions at 1 and 3 THz. The same property allowed also to verify experimentally that the axicon focus has a longitudinal extension much greater than that one exhibited by a benchmark cylindrical mirror with the same optical power. The axicon is thermo-mechanically stable up to a heating power of 270 mW, although it might be potentially exploited at higher powers with a minor degradation of the optical performances.

In the framework of mean field approximation, we consider a spin system consisting of two interacting sub-ensembles: spins interactions with in each sub-ensemble are ferromagnetic, while the inter-ensemble interactions are antiferromagnetic. We define the effective number of the nearest neighbors, and show that if the two sub-ensembles have the same effective number of the nearest neighbors, the classical form of critical exponents (, , , ) gives way to the non-classical form (, , , ), and the scaling function changes simultaneously. We demonstrate that this system allows for two second-order phase transitions and two first-order phase transitions. We observe that an external magnetic field does not destroy the phase transitions, but only shifts their critical points, allowing for control of the system’s parameters. We discuss the regime when the magnetization as a function of the magnetic field develops a low-magnetization plateau, and show that the height of this plateau abruptly rises to the value of one when the magnetic field reaches a critical value. Our analytical results are supported by a Monte Carlo simulation of a three-dimensional layered model.

Paraffin wax stores energy in the form of latent heat at a nearly constant temperature during melting and releases this energy during solidification. This effect is used in industrial energy storage. An unusual change in the shape of a melted droplet of paraffin wax placed on a relatively cold glass plate is studied. As the droplet solidifies, its upper surface becomes nearly flat and a dimple is formed in the center of this surface, making the droplet look like a fruit (pumpkins are more commonly shaped like this, but the authors prefer apples). A series of experiments, as well as physical and numerical modeling of the droplet's thermal state, taking into account the formation of a mushy zone between liquidus and solidus, made it possible to understand the role of gravity and gradual increase in viscosity and density of paraffin wax on changing the droplet shape and, in particular, to clarify the mechanism of formation of the dimple on its upper.

Purpose: Oxidative stress is responsible for over seventy five diseases and other harmful cytological challenges including cancer, type 2 diabetes mellitus, lipid peroxidation, distortion of cell membrane integrity, shortening of telomerase among others. Antioxidant potency of any plant is a very positive remedy to the debilitating effects of prooxidants and oxidants. The study was aimed at investigating the antioxidant potency of methanol extract of Pentaclethra macrophylla stem bark- in vitro and in vivo. Methods: Different phytochemicals were determined using standard methods. Nitric oxide, 1, 1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging activity, total antioxidant capacity and ferric reducing/anti-radical power were used to investigate the in vitro antioxidant activity. Catalase assay, superoxide dismutase, malondialdehyde and glutathione peroxidase were used to determine the in vivo antioxidant efficacy using six groups of five rats. Results: The result showed various quantities of phytochemicals, including antioxidant phytochemicals-flavonoids, tannins and total phenolics. The in vitro assay showed that 250 μg/ml of extract had the highest percentage inhibition of DPPH radical (93.93%). The 125 μg/ml had the highest scavenging activity of nitric oxide radical (49.47%) while 250μg/ml showed the least with 41.73%. Other methods showed various degrees of activity. The in vivo antioxidant showed that the principal mechanism of antioxidant activity is by modulating the iron-dependent catalase activity. Conclusion: Pentaclethra macrophylla has both in vitro and in vivo antioxidant activities and therefore is useful in ameliorating the debilitating effects of oxidants.

Small molecules that can modulate or stabilize cell-cell interactions are valuable tools for investigating the impact of collective cell behavior on various biological processes such as development/morphogenesis, tissue regeneration and cancer progression. Recently, we showed that budesonide, a glucocorticoid widely used as anti-asthmatic drug, is a potent regulator of stem cell pluripotency. Here we tested the effect of different budesonide derivatives and identified CHD-030498 as a more effective analogue of budesonide. CHD-030498 was able to prevent stem cell pluripotency exit in different cell-based models, including embryonic stem-to-mesenchymal transition, spontaneous differentiation and 3D gastruloid development, and at lower doses compared to budesonide.

Backgrounds: The field of Artificial Intelligence (AI) has seen a major shift in recent years due to the development of new Machine Learning (ML) models such as Generative Pre-trained Transformer (GPT) and AI which are progressively becoming part our everyday lives. GPT has achieved previously unheard-of levels of accuracy in most computerized language processing tasks and their chat-based variations. Aim: The aim of this study was to investigate the problem-solving abilities of ChatGPT using two sets of verbal insight problems, with a known performance level established by a sample of human participants. Material and Methods: A total of 30 problems labelled as “practice problems” and “transfer problems”, as listed by Ansburg and Dominowski (2000), were administered to ChatGPT. The answers provided by ChatGPT received a score of "0" for each problem answered incorrectly and a score of "1" for each correct response, as per the correct solution specified in Ansburg and Dominowski's (2000) study. The highest score that could be attributed to both the practice and transfer problems was 15 out of 15. In order to compare ChatGPT performance to the performance to that of human subjects, the solution rate for each problem (based on a sample of 20 subjects) was used, as indicated by Ansburg and Dominowski (2000). Results: The study highlighted that ChatGPT can be trained in out-of-the-box thinking and demonstrated potential in solving verbal insight problems. The global performance of ChatGPT equalled the most probable outcome for the human sample in both practice problems and transfer problems as well as upon their combination. Additionally, ChatGPT answer combinations were among the 5% of most probable outcomes for the human sample both when considering practice problems and pooled problem sets. These findings demonstrate that ChatGPT performance on both set of problems was in line with the mean rate of success of human subjects, indicating that it performed reasonably well. Conclusions: The use of transformer architecture and self-attention in ChatGPT may have helped to prioritize inputs while predicting, contributing to its potential in verbal insight problem-solving. ChatGPT has shown potential in solving insight problems, thus highlighting the importance of incorporating AI in psychological research. However, it is acknowledged that open challenges still exist. Indeed, further research is needed to fully understand the capabilities and limitations of AI in insight problem-solving.

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

Tubulin superfamily (TSF) proteins are widespread and known for multifaceted roles as cytoskeletal proteins underpinning many basic cellular functions including morphogenesis, division, and motility. In eukaryotes, tubulin assembles into microtubules, a major component of the dynamic cytoskeletal network of fibres, whereas the bacterial homolog FtsZ assembles the division ring at midcell. Functions of the lesser-known archaeal TSF proteins are beginning to be identified, and show surprising diversity, including homologs of tubulin and FtsZ, and a third archaea-specific family, CetZ, implicated in the regulation of cell shape and possibly other unknown functions. In this study, we defined sequence and structural characteristics of the CetZ family and CetZ1 and CetZ2 subfamilies, identified CetZ groups and diversity amongst archaea, and identified potential functional relationships through analysis of the genomic neighbourhoods of cetZ genes. At least three subfamilies of orthologous CetZ proteins were identified in the archaeal class Halobacteria, including CetZ1 and CetZ2 and a novel uncharacterized subfamily. CetZ1 and CetZ2 were correlated to one another and to cell shape and motility phenotypes across diverse Halobacteria. Amongst other known CetZ clusters in orders Archaeoglobales, Methanomicrobiales, Methanosarcinales, and Thermococcales, an additional uncharacterized group from Archaeoglobales and Methanomicrobiales affiliated strongly with Halobacteria CetZs, suggesting they originated via horizontal transfer. Subgroups of Halobacteria CetZ2 and Thermococcales CetZ genes were found adjacent to different type IV pili regulons, suggesting a potential utilization of CetZs by type IV systems. More broadly conserved cetZ gene neighbourhoods included nucleotide and cofactor biosynthesis (e.g., F420) and predicted cell surface sugar epimerase genes. The findings imply that CetZ subfamilies are involved in multiple functions linked to the cell surface, biosynthesis and motility.

The cuttlebone-like structure is a complex porous bionic structure with asymmetric sinusoidal S-shaped wall structure connecting laminar septa, and studies have shown that the cuttlebone-like structure has light weight, high strength and excellent energy absorption capability. It has become an important research to investigate the mechanical mechanism of cuttlebone-like structure and to design a bionic structure beyond nature structure based on it. In order to investigate the mechanical properties of the static compression and shearing processes of the cuttlebone-like structure, this paper establishes theoretical formulas and analyzes the influence of dimensionless parameters such as height-to-thickness ratio $\lambda$, period-to-thickness ratio $\xi$ and amplitude to period ratio $\eta$ on the compression and shearing processes with the help of ABAQUS finite element software.The parameter sensitivity analysis method was used to compare the important influence degree of each dimensionless parameter on the mechanical properties of the structure and to determine the relative optimal parameters of the structural mechanical properties under compression and shearing. Based on the relatively optimal parameter of the cuttlebone-like structure, the cross-sectional geometry of the structure is improved to build a new cuttlebone-like structure.The experimental results showed that the new cuttlebone-like structure with revised cross-section improved the mechanical properties of the cuttlebone-like structure.The study results are of theoretical guidance to enhance the mechanical properties and geometric design of cuttlebone-like structures.

Background: Developing an efficient and standardized method to isolate and characterize adipose-derived stem cells (ASCs) from the stromal vascular fraction (SVF) of the adipose tissue for clinical application represents one of the major challenges in cell therapy and tissue engineering. Methods: In this study, we proposed an innovative, non-enzymatic protocol to collect clinically useful ASCs within freshly isolated SVF from adipose tissue by centrifugation of the infranatant portion of lipoaspirate and to determine the characteristic cytofluorimetric pattern, prior to in vitro culture. Results: The SVF yielded a mean of 73,32 \pm\ 10,89% cell viability evaluated with CALCEINA-FITC, i.e. cell-permeant dye. The ASCs were positive for PC7-labeled mAb anti-CD34 and negative for both PE-labeled mAb anti-CD31 and APC-labeled mAb anti-CD45. The frequency of ASCs estimated according to the panel of cell surface markers used was 51,06%\ \pm 5,26% versus the unstained ASCs subpopulation that was 0,74%\pm0,84% (P<0.0001). The ASCs events/\muL were 1602,13/\muL \pm 731,87/\muL. Conclusion: Our findings suggested that ASCs found in freshly isolated adipose SVF obtained by centrifugation of lipoaspirate can be immunophenotypically identified with a basic panel of cell surface markers. These findings aimed to provide standardization and contribute to reducing the inconsistency on reported cell surface antigens of ASC derived from the existing literature.

It is introduced and studied para-Ricci-like solitons with potential Reeb vector field on almost paracontact almost paracomplex Riemannian manifolds. The special cases of para-Einstein-like, para-Sasaki-like and having a torse-forming Reeb vector field have been considered. It is proved a necessary and sufficient condition the manifold to admit a para-Ricci-like soliton which is the structure to be para-Einstein-like. Explicit examples are provided in support of the proven statements.

The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

The increasing detection of infections of Trypanosoma cruzi, the etiological agent of Chagas disease, in non-endemic regions beyond Latin America has risen to be a major public health issue. With an impact in the millions of people, current treatments rely on antiquated drugs that produce severe side effects and are considered nearly ineffective for the chronic phase. The minimal progress in the development of new drugs highlights the need for advances in basic research on crucial biochemical pathways in T. cruzi to identify new targets. Here, we report on the T. cruzi presenilin-like transmembrane aspartyl enzyme, a protease of the aspartic class in a unique phylogenetic subgroup with T. vivax separate from protozoans. Computational analyses suggests it contains 9 transmembrane domains and an active site with the characteristic PALP motif of the A22 family. Multiple linear B-cell epitopes were identified by SPOT synthesis analysis with Chagasic patient sera. Two were chosen to generate rabbit antisera, whose signal was primarily localized to the flagellar pocket, intracellular vesicles and endoplasmic reticulum in parasites by whole cell immunofluorescence. The results suggest that the parasitic presenilin-like enzyme could have a role in the secretory pathway and serve as a biomarker for infections.

According to its inner property, a crisis in the financial market can be considered as a collective behavior phenomenon. Through the prism of collective behavior, the crisis does not happen if the companies are independent of each other. In this work, cooperative movement processes in a stock market are investigated in a manner similar to that Vicsek first described collective behavior for self-propelled entities. To this end, a phase space is defined as the one in which the return of volume of transactions versus return of price is represented with each share in each day corresponding to a unique point in the space. The findings of the observation show that during times of crisis, the phase space is limited with the vector velocity of shares in the same direction. In contrast, on a regular day, the phase space is entirely accessible, with vector velocity aligned randomly. Moreover, in line with the Vicsek model, an order parameter is introduced, which evaluates the cooperative effects for the shares so that the higher the value of this parameter, the stronger the collective behavior of the shares.