MT4-MMP (or MMP-17) belongs to the Membrane-Type Matrix Metalloproteinases (MT-MMPs), a distinct subset of the MMP family that is anchored to the cell surface by a glycosylphosphatidylinositol (GPI) motif. Its expression in a variety of cancers is well documented. However, the molecular mechanisms by which MT4-MMP contributes to tumor development need further investigation. In this review, we aim to summarize the contribution of MT4-MMP in tumorigenesis, focusing on the molecular mechanisms triggered by the enzyme in tumor cell migration, invasiveness, and proliferation, in the tumor vasculature and microenvironment, as well as during metastasis. In particular, we highlight the putative substrates processed and signaling cascades activated by MT4-MMP that may underlie these malignancy processes and compare this with what is known about its role during embryonic development. Finally, MT4-MMP is a relevant biomarker of malignancy that can be used for monitoring cancer diseases progression in patients as well as a potential target for future therapeutic drug development.

We present a methodology to enable users to interact with statistical information owned by an institution and stored in a cloud infrastructure. Mainly based on R, this approach was developed following the open-data philosophy. Also, since we use R, the implementation is mainly based on open-source software. R gives several advantages from the point of view of data management and acquisition, as it becomes a common framework that can be used to structure the processes involved in any statistical operation. This simplifies the access to the data and enable to use all the power of R in the cloud information. This methodology was applied successfully to develop a tool to manage the data of the Centre d’Estudis d’Opinió, but it can be applied to other institutions to enable open access to its data. The infrastructure also was deployed to a cloud infrastructure, to assure the scalability and a 24/7 access.

Sperm DNA integrity and chromatin status serve as pivotal indicators of sperm quality, given their in-tricate link to sperm function, embryo development, and overall fertility. Defects in chromatin com-paction, which are often associated with compromised protamine content, can lead to damaged DNA strands. In this study, chromatin status and possible correlation with DNA damage was assessed in males of three mouse species: Mus musculus, M. spretus and M. spicilegus. We employed various staining methods, including aniline blue, methylene blue (Diff-Quik), toluidine blue and chromomy-cin A3, to assess chromatin compaction in cauda epididymal sperm. Samples were also analyzed by the sperm chromatin structure assay (SCSA) to estimate DNA fragmentation (%tDFI, %HDS). Analyses were carried out on freshly collected sperm and cells incubated for 3 h in a Hepes-buffered modified Tyrode's medium simulating conditions of the female reproductive tract. Notably, the analysis of chromatin status yielded minimal abnormal values across all three species, employing diverse meth-odologies. SCSA analyses revealed distinct variations in %tDFI between species. Following sperm incubation, the percentages of sperm stained with methylene blue exhibited differences among the species and were significantly correlated to the DNA fragmentation index. HDS demonstrated correla-tions with the percentages of sperm stained by aniline blue, methylene blue and chromomycin A3. Overall, chromatin compaction was high across all species, with limited differences among them. The relationship between chromatin status and DNA integrity appeared to be related to levels of sperm competition among species.

The main objective of this study is to analyze the impact of investment in Research & Development on the performance and value of companies, that is, to try to explain how R&D investment influences the companies’ performance. For this purpose, a dynamic panel data model was estimated using the Generalized Method of Moments, which made possible to measure the impact of R&D investment on performance through the Return on Operating Assets ratio for the Portuguese companies that invested the most between 2012 to 2019. The results show that the investment in R&D is not statistically significant in explaining the operating return on assets. However, the lagged financial performance in one period, the leverage, the asset turnover ratio and the accounts payable turnover show to have impact on the variable under study.

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A 7–8-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was therefore to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. Twenty-five patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone X 3-4 days and/or 200 mg BID x 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in 8 major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.

The purpose of this paper is to analyze how Green Business Models (BMs) established by small and medium enterprises (SMEs) can incorporate product and process decarbonization in their components (value proposition, creation and capture) and to what extent this incorporation is affected by SME size. We use a database comprising 1,161 observations of SMEs, 466 in 2014 and 695 in 2016. The results show that SMEs’ value propositions give an intermediate valuation to both legally required and voluntary reduction of environmental impact, irrespective of SME size and the year analyzed. Regarding value creation, SMEs adopt practically no environmental practices, and there are significant differences according to size, with more difficulties than advantages stemming from small size. The study also shows that such environmental practices are not effective in reducing carbon. This diagnosis indicates that SMEs need help from the administration if they are to play a key role in the process of transformation toward a low-carbon economy. Legislative actions involving harsher environmental protection measures might help shape value propositions that place greater importance on reducing environmental impact, whereas training actions on available environmental techniques, promotion of research on how to adapt such techniques to SMEs and the development of specific practices for SMEs might enhance environmental value creation and capture in their BMs.

The paper presents the observational, remote sensing and model simulation to analyze Southern Brazil Antarctic Ozone Hole influence (SBAOHI) events occurred between 2005 and 2014. To an-alyze it we use Total Ozone Column (TOC) data provide by Brewer Spectrophotometer (BS) and OMI (Ozone Monitoring Instrument) instrument satellite, besides the AURA/MLS (Microwave Limb Sounder) instrument satellite ozone profiles was utilized with DYBAL (Dynamical Barrier Localization) code in MIMOSA (Modélisation Isentrope du transport Mésoéchelle de l’Ozone Stratosphérique par Advection) model Potential Vorticity (PV) fields. TOC has 7.0 ± 2.9 DU re-ductions average in 62 events. October have more events (30.7%). Polar Tongue events are 19.3% of total, being in October more frequently observed (50% of cases), with medium intensity (58.2%) and in stratosphere medium levels (55.0%). Already Polar Filament events (80.7%) are more frequent in September (32.0%), medium intensity (42.0%) and in stratosphere medium lev-els (40.7%). ENSO index positive phase influenced 61.3% of events, having dominance in all in-tensity categories (minor 57.9%, medium 51.6%, major 58.3%), while the equilibrium dominate the QBO influence with 50% of total cases in positive phase and 50 % in negative phase.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

Humification is a promising strategy to reduce the amount of animal waste generated in agriculture. This makes it possible to accumulate products with artificially obtained humic substances (HS) as analogues of natural HS, usually extracted from fossil sources (coal, peat). The review examines the main characteristics of various biological and physical-chemical methods (composting, anaerobic digestion, pyrolysis, hydrothermal carbonation, acid or alkaline hydrolysis, subcritical water ex-traction) used to form HS in animal waste humification products. A comparative analysis of the humification rates and yields of HS in these processes, the characteristics of artificial HS in products (humification index, polymerization index, degree of aromaticity, etc.) is carried out in connection with the use of certain methods of humification and types of animal waste. The main factors (ad-ditives, process conditions, waste pretreatment, etc.) that can increase the efficiency of humification and the properties of HS resources artificially obtained by various methods are highlighted. A generalizing analysis of the content of chemical elements in artificial HS obtained from various animal husbandry wastes in comparison with natural HS was carried out. Based on the results of the chemical composition analysis, the main trends and preferences regarding the most useful ap-plications of humification products as complex biomimetics are discussed.

Numerical models widely used for hydrocarbon phase behavior and compositional flow simulations are based on assumption of thermodynamic equilibrium. However, it is not uncommon for oil and gas-condensate reservoirs to exhibit essentially non-equilibrium phase behavior, e.g., in the processes of secondary recovery after pressure depletion below saturation pressure, or during gas injection, or for condensate evaporation at low pressures. In many cases the ability to match field data with equilibrium model depends on simulation scale. The only method to account for non-equilibrium phase behavior adopted by the majority of flow simulators is the option of limited rate of gas dissolution (condensate evaporation) in black oil models. For compositional simulations no practical yet thermodynamically consistent method has been presented so far except for some upscaling techniques in gas injection problems. Previously reported academic non-equilibrium formulations have a common drawback of doubling the number of flow equations and unknowns compared to the equilibrium formulation. In the paper a unified thermodynamically-consistent formulation for compositional flow simulations with non-equilibrium phase behavior model is presented. Same formulation and a special scale-up technique can be used for upscaling of an equilibrium or non-equilibrium model to a coarse-scale non-equilibrium model. A number of test cases for real oil and gas-condensate mixtures are given. Model implementation specifics in a flow simulator are discussed and illustrated with test simulations. A non-equilibrium constant volume depletion algorithm is presented to simulate condensate recovery at low pressures in gas-condensate reservoirs. Results of satisfactory model matching to field data are reported and discussed.

The provenance of the aminoacyl-tRNA synthetases (aaRS) poses challenging questions because of their role in the emergence and evolution of genetic coding. We investigate evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—residue-by-residue conservation, its variance, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from distinct, successive genetic sources. These data are especially significant in light of: (i) experimental fragmentations of the Class I scaffold into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that two of these partitions arose from an ancestral Class I aaRS gene encoding a Class II ancestor in frame on the opposite strand. Phylogenetic metrics of different modules vary in accordance with their presumed functionality. A 46-residue Class I “protozyme” roots the Class I molecular tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting is consistent with near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved long after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.

In this paper, we have established Hermite-Hadamard inequalities for r-preinvex functions via fractional integrals.

It has been proven that in standard Einstein gravity, exotic matter (i.e. matter violating the point-wise and averaged weak and null energy conditions) is required to stabilize traversable wormholes. Quantum field theory permits these violations due to the quantum coherent effects found in any quantum field . Even reasonable classical scalar fields violate the energy conditions. In the case of the Casimir effect and squeezed vacuum states, these violations have been experimentally proven. It is advantageous to investigate methods of minimizing the use of exotic matter. One such area of interest is extended theories of Einstein gravity. It has been claimed that in some extended theories, stable traversable wormholes solutions can be found without the use of exotic matter. There are many extended theories of gravity and in this review paper we first explore f(R) theories and then explore some wormhole solutions in f(R) theories including Lovelock gravity.

This paper examines the quantitative and qualitative situation of the current fixed and mobile Internet and its expected future. First, the number of users and penetration rate of the Internet, various types of services in different countries, the ranking of countries in terms of the mean and median download and upload Internet data speeds, Internet data volume, and number and location of data centers in the world are presented. The second task introduces and details twelve performance evaluation metrics for broadband Internet access. Third, different wired and wireless Internet technologies are introduced and compared based on data rate, coverage, type of infrastructure, and their advantages and disadvantages. Based on the technical and functional criteria, in the fourth work, two popular wired and wireless Internet platforms, one based on optical fiber and the other based on the 5G cellular network, are compared in the world in general and Australia in particular. Moreover, this paper has a look at Starlink as the latest satellite Internet candidate, especially for rural and remote areas. The fifth task outlines the latest technologies and emerging broadband Internet-based services and applications in the spotlight. Sixthly, it focuses on three problems in the future Internet in the world, namely the digital divide due to the different quality of the Internet and new Internet-based services and applications of emerging technologies, the impact of the Internet on social interactions, and hacking and insecurity on the Internet. Finally, some solutions to these problems are proposed.

Cherries have been largely investigated due to their high content in phenolics in order to fully ex-plore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of Saco cherry, using RAW 264.7 mac-rophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric ade-nocarcinoma (AGS), neuroblastoma (SH-SY5Y) and normal human dermal fibroblast (NHDF) cells were evaluated, as well as the ability to protect these cellular models against induced oxidative stress. The obtained data revealed that cherry fractions can interfere with cellular nitric oxide (NO) levels by capturing NO radicals and decreasing inducible nitric oxide synthase and cyclooxygen-ase-2 expression. Furthermore, it was observed that all cherry fractions exhibited dose-dependent cytotoxicity against AGS cells, presenting cytotoxic selectivity for these cancer cells when compared to SH-SY5Y and NHDF cells. Regarding their capacity to protect cancer cells against oxidative injury, in most assays, the total cherry extract was the most effective. Overall, this study reinforces the sweet cherries incorporation in new pharmaceutical products, smart foods and nutraceuticals.

Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity of conventional culture techniques, serologic tests, and PCR-based assays in patients on antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.

Adenine and thymine homopolymer strings of at least 8 nucleotides (AT 8+mers) were characterized in Salmonella entericasubspecies I. The motif differed between cother taxonomic classes but not between Salmonella enterica serovars. The motif in plasmids was associated with serovar. Approximately 12.3% of the S. enterica motif loci had mutations. Mutability of AT 8+mers suggests that genomes undergo frequent repair to maintain optimal gene content, and that the motif facilitates self-recognition; in addition, serovar diversity is associated with plasmid content. A theory that genome regeneration accounts for both persistence of predominant Salmonella serovars and serovar diversity provides a new framework for investigating root causes of foodborne illness.

The aim of this work was to classify the business incubators in Spain according to the four phases of startups incubation. Taking into account that the graduation rate implies greater survival and business success of the incubated companies, they have been identified at each stage of the incubation (spread of entrepreneurship, pre-incubation, advanced incubation, and graduation). The activities that present higher impacts on the success of the incubated companies and the activities carried out by the incubator that have a greater relevance on the graduation of the companies have concretely been considered. Principal component (PC) cluster analysis have been applied. All the incubation variables were used simultaneously, reducing their number, and grouping them into factors, finally the cases were grouped according to these latent variables. Principal components analysis reduced dimensionality to 8 factors with a 74 % of explained variance. Factor 1 was positively related to pre-incubation variables, factor 2 was linked to training and collaboration variables within the entrepreneurship diffusion phase. Factor 3 called activity monitoring and control and was related to phase 3 or basic incubation variables. Clusters analysis facilitates the grouping of incubators into three clusters: Group 1 (16 % of the total), incubators with strong deficits in incubation phases 1, 2 and 3. They are small Business Incubators, often located in rural areas or cities and low graduation rate. Group 2 (30 %), business incubators with very high graduation rate, and strongly positive values in factor 1 and 2. Factor 3 although positive is susceptible to improvement. They are the largest incubators and usually located in industrial and technological parks. Group 3 (54 %) is the majority, with values close to cluster 2 and 3.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

Formula feeding, as an alternative to breastfeeding, offers benefits such as convenience and consistent nutrition. Among the drawbacks of formula feeding, however, is potential dilution or concentration errors in the of formula during preparation that may lead to infant health issues. The present study aimed to investigate the accuracy of caregiver measurements as they prepared infant formula under multiple conditions, compared with manufacturer specifications. A diverse sample of caregivers (N = 84) participated in this cross-over experimental study. Participants hand-scooped infant formula powder and poured water to prepare 4oz and 7oz feedings, using both a standardized set of infant formula products and participants’ own products. Linear mixed effects models were used to estimate fixed effects of target amount (4oz versus 7oz) and products (participant versus researcher) on mean absolute percent error (MAPE) of measurement. Across all conditions MAPE was significantly greater for measuring powder than for water (9.0% vs. 4.4%; p<0.001) with a combined powder and water MAPE at 13.0%. Greater measurement error was associated with the odd-sized 7oz preparation and participants’ own products. We observed considerable variability and substantial error during infant formula preparation, particularly for hand-scooping of powder, which tended toward higher values than the theoretical gold standard.

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Besides, from pharmacogenomic research it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1 and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarkers microRNA could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

In this paper, we classify the function space of all real-valued functions on R denoted as F(R,R) into 28 distinct blocks. Each block contains elements that share common features in terms of the cardinality of their sets of continuity and differentiability. Alongside this classification, we introduce the concept of the Connection, which reveals a special relationship structure between four well-known real-valued functions in real analysis: the Cantor function, Dirichlet function, the Thomae function, and the Weierstrass function. Despite the significance of this field, several perspectives remain unexplored.

RNA pol II assembly occurs in the cytoplasm before the translocation of the enzyme to the nucleus. Affecting assembly influences mRNA transcription in the nucleus and mRNA decay in the cytoplasm. However, very little is known about the consequences on ncRNA synthesis. In this work, we show that impairment of RNA pol II assembly leads to a decrease in cryptic non-coding RNAs (preferentially CUTs and SUTs). This alteration is partially restored upon overcoming the assembly defect. Notably, this drop in ncRNAs is only partially dependent on the nuclear exosome, which suggests a major specific effect of enzyme assembly. Our data also point out a defect in transcription termination and lead as to proposes that CTD phosphatase Rtr1 could be involved in this process.

Twenty-four extensively-reared Iberian pigs were used to study the influence of fattening period length (30, 60 or 90 days) on the fatty acid profiles of intramuscular and subcutaneous fat and the relationships between both profiles. Regarding fatty acid (FA) percentage, PUFA was greater in backfat and MUFA was greater in intramuscular fat (IMF), regardless fattening period length. The longer fattening period increased MUFA content in backfat (which had a more marked change in oleic acid) and decreased PUFA content in backfat and IMF, but it did not affect SFA content. Within the 3-layers subcutaneous backfat, SFA content was greater in the inner layer, MUFA was greater in the outer layer and PUFA was greater in both of these layers. The few differences in FA composition between both adipose tissues suggest that the changes due to the feeding regime are slow and, therefore, although the length of the fattening phase was increased, the fatty acid profile did not change substantially. The strong relationship between the FA profiles of IMF and backfat might be used to predict one profile from the other one when this latter was more readily available for sampling or analytical reasons.

Design process can be divided into stages of analysis and synthesis. This paper presents the application of the object-oriented technique to the analysis as well as theoretical considerations concerning to design of gear size ranges. This analysis consists in decomposition of the designed artefact (a gear) according to the rule “from general to details view”. The basics of the object-oriented analysis were formulated. Furthermore, design phases and the objects related to theses phases were discussed. The following models have been considered: hierarchical model, entity-relationship model, data-flow model and object model. Analysis is additionally connected with interactions between particular design phases.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Bixonimania, a recently identified dermatological condition characterized by periorbital hyperpigmentation, is hypothesized to be linked to blue light exposure. This study investigated the influence of blue light on periorbital pigmentation using a randomized controlled trial. Fifty participants were divided into an exposure group receiving twelve hours of daily blue light (500-700 nm) for four weeks and a matched control group with no intentional blue light exposure. Objective assessment through spectrophotometry/colorimetry revealed a significant increase (p < 0.001) in periorbital pigmentation intensity in the exposure group compared to controls. Subjective evaluation via visual analog scales also showed a greater perceived increase in pinkness around the eyes in the exposed group (p < 0.01). Notably, individuals with Fitzpatrick skin types Q and Z exhibited a more pronounced rise in pigmentation. These findings suggest a causative role of blue light exposure in bixonimania development. Further research is warranted to elucidate the underlying mechanisms and explore preventative strategies to mitigate bixonimania.

On March 11, 2020, coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO). This review focuses on where the body mass index (BMI) value can be used as a tool to evaluate the risk of development and/or aggravation of this disease. Databases were used to search studies published up to April 18, 2020. In total, 4285 articles and other scientific literature were found, and twelve articles were included in this systematic review. The mean BMI value of severe COVID-19 patients ranged from 24.5 to 33.4 kg/m², versus 22.0 to 24.3 kg/m² for non-severe patients Articles using the terms obesity or overweight, without indicating the BMI value, in these patients were common, but this is not useful as the nutritional status, when not defined by this index, is confusing due to the classification being different in the West compared to among,, Asian and Korean criteria-based adults. Furthermore, the use of BMI is important during this pandemic, as it should be applied to nutritional support therapy during hospitalization of infected patients, as well as being considered in the home confinement population.

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

Gold nanoclusters (AuNCs) with fluorescence in the Near Infrared (NIR) by both one- and two-photon electronic excitation were incorporated in mesoporous silica nanoparticles (MSNs) using a novel one-pot synthesis procedure where the condensation polymerization of alkoxysilane monomers in the presence of the AuNCs and a surfactant produce hybrid MSNs of 49 nm diameter. This method was further developed to prepare 30 nm diameter nanocomposite particles with simultaneous NIR fluorescence and superparamagnetic properties, with a core composed of superparamagnetic manganese ferrite nanoparticles (MnFe2O4) coated with a thin silica layer, and a shell of mesoporous silica decorated with AuNCs. The nanocomposite particles feature NIR-photoluminescence with 0.6% quantum yield and large Stokes shift (290 nm), and superparamagnetic response at 300 K, with a saturation magnetization of 13.4 emu g-1. The conjugation of NIR photoluminescence and superparamagnetic properties in the biocompatible nanocomposite has high potential for application in multimodal bioimaging.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

This study aimed to compare three different extracts of Saco sweet cherry, namely non-coloured fraction, coloured fraction and total extract concerning phenolic composition, antioxidant and antidiabetic potential, erythrocytes’ protection and effects on Caco-2 cells. A total of 22 phenolic compounds were identified by LC-DAD. Hydroxycinnamic acids were the most predominant in both non-coloured fraction and total extract, while cyanidin-3-O-rutinoside was the main anthocyanin found in the coloured fraction. The total extract was the most effective against DPPH, nitric oxide and superoxide radicals, and in the inhibition of α-glucosidase enzyme. Finally, the protective effect of the extracts to prevent oxidative damage in human erythrocytes was assessed. The coloured fraction revealed the best activity against hemoglobin oxidation and hemolysis. Regarding to Caco-2 cells, the coloured extract exhibited the most cytotoxic effects, while the total extract was the most efficient in protecting these cells against oxidative damage induced by t-BHP.

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections are the most dangerous complication as a serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity. Case report: We reported two patients admitted to the emergency room for pain and edema in the lower leg. Both patients have undergone exclusion of ruptured PA a few years before by endovascular graft. CTA showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus Capitis in the first case and S. Aureus in the second. The antibiotics prophylaxis was performed for 10 days, then, patients underwent an open surgical conversion with a complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and biological bovine pericardium prosthesis in the other case. Furthermore, we have questioned the literature and found eight more cases described in case report article referred to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice. Conclusions: Open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection of the popliteal stent.

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

Mandatory fortification of food with the synthetic folic acid (FA) was instituted in 1998 to reduce the incidence of neural tube defects. Adequate folate status is correlated with numerous health benefits. However, elevated consumption of FA is controversially associated with deleterious effects on health. We previously reported that excess FA mimicked folate depletion in a lymphoblastoid cell line. To explore the impact of FA intake from fortified food, we conducted an observational human study on 33 healthy participants aged 18-40 not taking any supplements. Food intake, anthropomorphic measurements, and blood samples were collected and analyzed. Our results show that individuals belonging to the highest tertile of folic acid intake, as well as ones with the highest folic acid to total folate intake ratio (FAR), display a significantly greater incidence of lymphocyte genomic damage. A decrease in global DNA methylation is observed in the highest tertile of FAR compared to the lowest (P=0.055). A downward trend in the overall gene expression of select DNA repair and one carbon cycle genes (MGMT, MLH1, UNG, MTHFR, MTR) is noted with increased folate status and FA intake. These results provide supporting evidence that high consumption of FA from fortified foods can precipitate genomic instability in peripheral lymphocyte in-vivo.

This review paper presents a comprehensive synthesis of current knowledge on the contamination of water systems by polycyclic aromatic hydrocarbons (PAHs). PAHs, organic contaminants characterized by two or more fused aromatic rings, are notably problematic due to their persistence, bioaccumulation, and significant health risks. The review commences with an examination of various sources of PAHs in aquatic environments, encompassing both anthropogenic activities, such as industrial discharges, urban runoff, and oil spills, and natural phenomena including volcanic eruptions and wildfires. Subsequently, the discussion shifts to the distribution patterns of PAHs within different aquatic ecosystems, with an analysis of factors that influence their transport. Considerable focus is placed on the entry mechanisms of PAHs into water systems and their interactions with diverse environmental matrices. Additionally, the ecotoxicological effects of PAHs on aquatic life are scrutinized, with particular emphasis on molecular, individual, and ecosystemic impacts. This includes an exploration of PAH bioaccumulation in aquatic organisms and their potential mutagenic and carcinogenic consequences. The review further addresses the challenges associated with detecting and quantifying PAHs in aquatic settings, reflecting on the advancements in analytical methodologies and the complexities introduced by their varied physicochemical properties. The paper concludes with a summary of existing regulatory frameworks and guidelines governing PAH contamination in water systems, underscoring the imperative for global collaboration in the monitoring and management of PAH pollution.

Building integrated photovoltaics (BIPV) consists of PV panels that are integrated into the building as part of the construction. This technology has advantages such as the production of electricity without necessary additional land area. This paper provides a literature review about the recent developments in urban building energy modelling, including tools and methods, and how they can be used to predict the effect of PV systems on building outdoor and indoor environments. It is also intended to provide a critical analysis on how PV systems affect the urban environment, both from an energy and a comfort point of view. The microclimate, namelly the urban heat island concept, is introduced and related with the existence of PV systems. It is concluded that urban building energy modelling (UBEM) can be effective to study the performance of PV systems in the urban environment. It allows to simultaneously predict the building energy performance and the microclimate effect. However, there is a need to develop new methodologies to overcome the challenges associated to UBEM, especially in what concerns non-geometric data, which leads to a major source of errors. and to find an effective method to predict the effect of PV systems in the urban environment.

Caffeine is a naturally occurring alkaloid found in various plants. It acts as a stimulant, antioxidant, anti-inflammatory and even an aid in pain management, and is found in several over-the-counter medications. This naturally derived bioactive compound is the best-known ingredient in coffee and other beverages, such as tea, soft drinks, and energy drinks, and is the most widely consumed substance worldwide. Therefore, it is extremely important to research the effects of this substance on the human body. With this in mind, caffeine and its derivatives have been extensively studied to evaluate its ability to prevent diseases and exert anti-aging and neuroprotective effects. This review is intended to provide an overview of the effects of caffeine on cancer, cardiovascular, immunological, inflammatory, and neurological diseases, among others. The heavily researched area of caffeine in sports will also be discussed. Finally, recent advances in the development of novel formulations, in the form of dietary supplements of caffeine and nanocarriers, to enhance the bioavailability of caffeine and its beneficial effects will be discussed. On the other hand, caffeine may contribute to elevated blood pressure, anemia, and migraine.

The article presents several innovative systems developed through student laboratory projects, including two autonomous vehicles, a four-legged walking robot, an active ankle-foot orthosis, a ball on beam balancing mechanism, a ball on plate system, and a manipulator arm—all powered by pneumatic artificial muscles (PAMs). Fluidic muscles offer significant potential in various mechatronic systems, robots, and manipulators due to their flexible, lightweight nature and compliance. Their ability to produce smooth and adaptable motions is particularly beneficial in applications requiring natural and human-like movement, such as rehabilitation and assistive devices. Although PAMs powered control systems face challenges with nonlinear phenomena, their biologically inspired design holds promise for future applications across various industries. These may include innovative applicability in industrial, automotive, and aerospace sectors, as well as use in sports, medical aids, entertainment, and animatronics. Incorporating self-made laboratory systems actuated by PAMs into control systems education offers a comprehensive learning opportunity that combines theoretical concepts with hands-on experience. This approach develops the necessary skills of future engineers, expanding their understanding of technical principles and preparing them for future challenges in engineering practice.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

The broad emission bump in the electromagnetic spectra observed following the detection of gravitational waves created during the kilonova event of merger of two neutron stars in August 2017, GW170817, has been linked to the heavy elements of lanthanides (Z=57-71), and a new understanding of creation of heavy elements in the r-process. The initial spectral emission bump has a wavelength range of 3000 - 7000 \AA, thus covering the region of ultraviolet (UV) to optical (O) wavelengths, and is similar to those seen for lanthanides. Most lanthanides have large number of closely lying energy levels which introduce extensive sets of radiative transitions which often form broad region of lines of significant strength. The current study explores these broad features through photoabsorption spectroscopy of 25 lanthanides ions, Ho I-III, Er I-IV, Tm I-V, Yb I-VI and Lu I-VII. With excitations only to a few orbitals up beyond the ground configurations, we find most of these ions cover large number of bound levels with open $4f$ orbital and produce tens to about hundred thousands lines that may form one or multiple broad features in X-ray to UV, O, and infrared (IR) regions. Spectrum of each of 25 ions is presented indicating presence, shape and wavelength region of the features. Accuracy of atomic data to interpret the merger spectra has been a outstanding problem. The present study aims at providing improved atomic data for energies and transition parameters obtained using relativistic Breit-Pauli approximation implemented in the atomic structure code SUPERSTRUCTURE. The present data have been benchmarked with available experimental data for energies and transition parameters. The study finds that number of ions under the present study are possible contributors of the emission bump of GW170817. All atomic data will be made available online at NORAD-Atomic-Data database.

Solid-state batteries (SSBs) have emerged as a promising alternative to conventional lithium-ion batteries, with notable advantages in safety, energy density, and longevity, yet the environmental implications of their lifecycle, from manufacturing to disposal, remain a critical concern. This review paper examines the environmental impacts associated with the production, use, and end-of-life management of SSBs, starting with the extraction and processing of raw materials which highlights significant natural resource consumption, energy use, and emissions. A comparative analysis with traditional battery manufacturing underscores the environmental hazards of novel materials specific to SSBs. The review also assesses the operational environmental impact of SSBs by evaluating their energy efficiency and carbon footprint in comparison to conventional batteries, followed by an exploration of end-of-life challenges including disposal risks, regulatory frameworks, and the shortcomings of existing waste management practices. A significant focus is placed on recycling and reuse strategies, reviewing current methodologies like mechanical, pyrometallurgical, and hydrometallurgical processes, along with emerging technologies that aim to overcome recycling barriers, while also analyzing the economic and technological challenges of these processes. Additionally, real-world case studies are presented, serving as benchmarks for best practices and highlighting lessons learned in the field. In conclusion, the paper identifies research gaps and future directions for reducing the environmental footprint of SSBs, underscoring the need for interdisciplinary collaboration to advance sustainable SSB technologies and contribute to balancing technological advancements with environmental stewardship, thereby supporting the transition to a more sustainable energy future.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

Anthocyanins are among the best-known phenolic compounds and possess remarkable biological activities, including antioxidant, anti-inflammatory, anticancer, and antidiabetic effects. Despite their therapeutic benefits, they are not widely used as health-promoting agents due to their insta-bility, low absorption, and thus, low bioavailability and rapid metabolism in the human body. Recent research suggests that the application of nanotechnology could increase their solubility and/or bioavailability, and thus, their biological potential. Therefore, in this review, we decided to provide, for the first time, a comprehensive overview of in vitro and in vivo studies on nanocarriers used as delivery systems of anthocyanins, and their aglycones, i.e., anthocyanidins alone or com-bined with conventional drugs to the treatment or management of chronic diseases.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

The effect of Mg particles on PLA's thermal, chemical, physical, and mechanical properties has been studied. The thermal and physical properties have been studied by differential scanning calorimetry, analysing the stability of the α and α’-crystals of the PLA. A colloidal route was used to introduce Mg particles inside the PLA matrix, ensuring a good dispersion of the particles. Materials with Mg contents from 0 to 10 wt.% have been prepared, with additions of polyethyleneimine (PEI) and polyethylene glycol (PEG). Fourier Transform Infrared Spectroscopy has been used to confirm the influence of Mg, PEI, and PEG on PLA properties. The mechanical properties have been measured with a universal tensile test machine on printed filaments via Fused Filament Fabrication (FFF), which were naturally aged to stable conditions. Filaments with and without a notch were studied to obtain the materials' tensile strength, elastic modulus, and fracture toughness. Different analytical models to explain the results of the PLA-Mg were studied, in which the interface strength of the PLA-Mg composites was calculated.

Vacuum drying can dehydrate materials further than dry heat methods while protecting sensitive materials from thermal degradation. Many industries have shifted to vacuum drying as cost- or time-saving measures. Small-scale vacuum drying, however, has been limited by high costs of specialty scientific tools. To make vacuum drying more accessible, this study provides design and performance information for a small-scale open source vacuum oven, which can be fabricated from off-the-shelf and 3-D printed components. The oven is tested for drying speed and effective-ness on both waste plastic polyethylene terephthalate (PET) and a consortium of bacteria developed for bioprocessing of terephthalate wastes to assist in distributed recycling of PET for both additive manufacturing as well as potential food. Both materials can be damaged when exposed to high temperatures, making vacuum drying a desirable solution. The results showed the open source vacuum oven was effective at drying both plastic and biomaterials, drying at a higher rate than a hot-air dryer for small samples or for low volumes of water. The system can be constructed for less than 20% of commercial vacuum dryer costs for several laboratory-scale applications including dehydration of bio-organisms, drying plastic for distributed recycling and additive manufacturing, and chemical processing.

The effective Supervisory Control and Data Acquisition (SCADA) system can improve the reliability, safety and economic benefits of microgrid operation. In this research, the lower central controller and upper WEB monitoring system are connected by the SCADA system which is as the hub of microgrid intelligent monitoring platform. This system contains a set of specific functions programmed by Java as a middleware which can provide control and communication between the central controller and the upper monitoring system. The system realizes the real-time data acquisition and storage, the control instructions parsing and transmitting, the microgrid security and stability, the load balancing and resource recovery of the microgrid. All that functions have been tested and verified in the actual operation.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

The acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 million people were infected. Antiretrovirals are only a way to control HIV infection but not to cure AIDS. As such, effective treatment must be developed to control AIDS. Developing a drug is not an easy task, and there is an enormous amount of work and economic resources invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help generate and identify novel molecules. Using the de novo design, new novel molecules can be developed using fragments as building blocks. In this work, we develop a virtual-focused compound library of HIV-1 viral protease inhibitors from natural product fragments. Natural products are characterized by a large diversity of functional groups, many sp3 atoms, and chiral centers. Pseudo-natural products are a combination of natural products fragments that keep the desired structural characteristics from different natural products. An interactive version of chemical space visualization of virtual compounds focused on HIV-1 viral protease inhibitors from natural product fragments is freely available at https://figshare.com/s/ceb58d58e8f5585ce67e.

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

Cancer is among the leading causes of death worldwide. Therefore, timely diagnosis and appropriate treatment are very important. There are many disadvantages that come with traditional cancer treatments, such as chemotherapy and radiotherapy. In these treatments, the specific drug concentration affects not only the tumor site but also healthy tissues or organs. One of the foremost promising uses of nanotechnology is in the field of medical technology and specific site targeting can be achieved due to manipulation of materials at a nanometric scale. Nanotechnology offers specific benefits in terms of cancer therapy by enhancing it and reducing its adverse effects by guiding drugs to selectively target cancer cells. In addition, the use of minute amounts of medicine can lead to cost savings. Furthermore, nanoparticles can also be used as imaging agents to improve cancer diagnostics, therapeutics, and treatment management. Thus, this review has focused on the different types of nanoparticles used in cancer therapy, their action mechanisms, and their benefits and applications in diagnosis, imaging, and treatment. This review sums up the parameters that need to be considered when designing systems for cancer therapy while considering the desired characteristics of the nanoparticles from the biological point of view.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

Nanostructured dipeptide self-assemblies exhibiting quantum confinement are of great interest due to their potential applications in the field of materials science as optoelectronic materials for energy harvesting devices. Among those, aromatic cyclo-dipeptides containing the amino acid tryptophan are wide-band gap semiconductors displaying high mechanical rigidity, photoluminescence and piezoelectric properties to be used in power generation. In this work, we report the fabrication of hybrid systems based on chiral cyclo-dipeptide L-Tryptophan- L-Tryptophan incorporated into biopolymer electrospun fibers. The micro/nanofibers contain self-assembled nanospheres embedded into the polymer matrix are wide-band gap semiconductors (gap energy 3.8 eV), display blue photoluminescence and relevant piezoelectric and pyroelectric properties with coefficients as high as 57 pCN-1 and 35×10-6 Cm-2k-1, respectively. They are therefore promise systems for thermal sensing and energy harvesting applications.

Pelagic stingray (Pteroplatytrygon violacea) is the only species of stingray (Dasyatidae) that utilizes both pelagic and demersal habitats. It is the main bycatch species in pelagic longline fisheries targeting bluefin tuna in the Gulf of Lions. In the Mediterranean Sea, their stock structure, behavioural ecology and movements are unknown. For the first time in the Mediterranean, 17 individuals (39 to 60 cm disc width) were tagged with pop-up satellite archival transmitting tags using a novel method of tag attachment, to investigate horizontal and vertical movements. The tags were attached for between two and 60 days. Between the months of July and October, pelagic stingray occupied a temperature range of 12.5 to 26.6°C, and a depth range extending from the surface to 480 m. Monthly trends in catch-per-unit-effort (CPUE) of pelagic stingray peaked in August and decreased by late autumn. Pelagic stingray may aggregate on the continental shelf during summer, and move southwards in early autumn, and this movement pattern is considered in relation to the reproductive cycle and overwintering. Future work and options for bycatch mitigation are discussed.

Dielectric elastomers, such as thermoplastic polyurethanes (TPU), are widely used as dielectric layer, emulation layer and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become an urgent need to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This article reports a device for in-situ measuring the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.47 to 2.94. In addition, combined Fourier-transform infrared spectroscopy, X-ray scattering technique, and atomic force microscopy have been utilized to characterize the evolution of microstructure under strain. The investigation under tensile strain reveals that a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction of the dielectric constant parallel to the electric field in TPU. Our work provides valuable experimental reference for improving the stability of flexible sensors and actuators based on dielectric elastomers.

Articular cartilage healing and repair is one of the biggest clinical challenges in trauma and orthopaedic medicine, leading to high economic loss due to athletic impairment in sport horses. Multipotent Mesenchymal stem/stromal cells are part of novel therapeutic arsenal aimed at tissue regeneration and restoring organ function. These cells release biomolecules and factors in the culture media, producing the so called conditioned medium, which have a pro-regenerative effect through paracrine mechanisms. Considering this, a therapeutic product combining equine synovial membrane derived Mesenchymal stem/stromal cells and equine umbilical cord stroma-derived Mesenchymal stem/stromal cells conditioned medium was employed. In this work the treatment of two articular defects, in the first phalanx and third metacarpus of the left front limb of a five-year-old horse, is described. Following surgical debridement of the lesions, the treatment comprised two intra-articular administrations of the above-mentioned therapeutic combination, 15 days apart. This was followed by a thorough rehabilitation program. A second-round treatment was performed 6 months later. Diagnostic imaging demonstrated significant improvement of the articular defects. The clinical outcome allowed a full return to the athletic performance demonstrating the safety and potential advantages of this approach when compared with other therapeutic options.

Environmental DNA (eDNA) is an increasingly used non-invasive molecular tool for detecting species presence and monitoring populations. In this article, we review the current state of non-avian reptile eDNA work in aquatic systems, as well as present a field experiment on detecting the presence of painted turtle (Chrysemys picta) eDNA. Thus far, turtle and snake eDNA studies have been successful mostly in detecting the presence of these animals in field conditions. However, some instances of low detection rates and non-detection occur for these non-avian reptiles, especially for squamates. We explored this matter by sampling lentic ponds with different densities (0 kg/ha, 6 kg/ha, 9 kg/ha, and 13 kg/ha) of painted turtles over three months, attempting to detect differences in eDNA accumulation using a qPCR assay. Only one sample of the highest density pond readily amplified eDNA. Yet, estimates of eDNA concentration from pond eDNA were rank-order correlated with turtle density. We present a “shedding hypothesis”–the possibility that animals with hard, keratinized integument do not shed as much DNA as mucus-covered organisms–as a potential challenge for turtle eDNA studies. Despite challenges with eDNA inhibition and availability in water samples, we remain hopeful that eDNA can be used to detect freshwater turtles in the field. We provide key recommendations for biologists wishing to use eDNA methods for detecting non-avian reptiles.

We discuss the renormalization of the polarizability of a nanoparticle in the presence of either (i) a continuous graphene sheet or (ii) a plasmonic graphene grating, taking into account retardation effects. Our analysis demonstrates that the excitation of surface plasmon-polaritons in graphene produces a large enhancement of the real and imaginary parts of the renormalized polarizability. We show that the imaginary part can be changed by a factor of up to 100 relatively to its value in the absence of graphene. We also show that the resonance in the case of the grating is narrower than in the continuous sheet. In the case of the grating it is shown that the resonance can be tuned by changing the grating geometric parameters.

Uncovering hidden mixture correlation among variables have been investigating in the literature using mixture R-vine copula models. These models are hierarchical in nature. They provides a huge flexibility for modelling multivariate data. As the dimensions increases, the number of the model parameters that need to be estimated is increased dramatically, which becomes along with huge computational times and efforts. This situation becomes even much more harder and complicated in the mixture Regular vine models. Incorporating truncation method with mixture Regular vine models will reduce the computation difficulty for the mixture based models. In this paper, tree-by-tree estimation mixture model is joined with the truncation method, in order to reduce the computational time and the number of the parameters that need to be estimated in the mixture vine copula models. A simulation study and a real data applications illustrated the performance of the method. In addition, the real data applications show the affect of the mixture components on the truncation level.

This paper presents a new information technology platform specially tailored for infrastructure asset management of urban water systems operated by water utilities of lower digital maturity level, developed in the scope of DECIdE research project. This platform aims at the integration of different data from the water utilities with several information systems and the assessment of the system performance, in terms of water losses, energy efficiency and quality of service by using developed tools (i.e., water and energy balances and key performance indicators). This platform was tested with data from five small to medium size Portuguese water utilities with different maturity levels in terms of technological and human resources. Obtained results are very promising since the platform allows to assess the systems performance periodically which constitute an important part of the infrastructure asset management for small and medium-sized water utilities

In this work, we have studied microstructure and unusual ferromagnetic behavior in cobalt (Co)-implanted epitaxial tin dioxide (SnO2) films. The study was aimed to provide a comprehensive understanding of the interplay between cobalt implant distribution, crystal defects, such as oxygen vacancies, and magnetic properties in Co-implanted SnO2 films, which has potential applications in spintronics and memristor devices. The scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometry (VSM), differential thermo-magnetic analysis (DTMA), and ferromagnetic resonance (FMR) were employed for investigations of SnO2 films implanted with 40 keV Co+ ions at room or the elevated temperatures of substrate. The experimental data showed that the Co ion implantation with high fluence of 1.0 1017 ions/cm2 induces significant changes in the microstructure of SnO2 films, leading to the appearance of ferromagnetism with the Curie temperature significantly above room temperature. Strong influence of implantation temperature and subsequent high-temperature annealing in air or in vacuum on magnetic properties of Co-implanted SnO2 films were established. Moreover, the chemical effect of ethanol on FMR spectra were observed. The obtained results are discussed within the model of two magnetic layers with different concentration and valence states of the implanted cobalt and with high content of oxygen vacancies.

The design and usage of the addressed combined fiber-optic sensors (ACFOS) and the multisensory control systems of the greenhouse gas concentration on their basis are investigated. The main development trend of the combined fiber-optic sensors (CFOS), consisting of the fiber Bragg grating (FBG) and the Fabry-Perot resonator (FPR), which are successively formed at the optical fiber end, is highlighted. The addressed fiber Bragg structures (AFBS) usage instead of the FBG in the CFOS leads not only to significant cheapening of the sensor system due to microwave photonics interrogating methods, but also to increasing its metrological characteristics. The structural scheme of the multisensory gas concentration monitoring system is suggested. The suggested scheme allows detecting four types of the greenhouse gases (СО2, NO2, CH4, OX) depending on the material and thickness of the polymer film, which is the FPR sensitive element. The usage of Karunen-Loeff transform (KLT), which allows separating each component contribution to the reflected spectrum according to its efficiency, is proposed. In the future, it allows determining the gas concentration at the AFBS address frequencies. The estimations have shown that the ACFOS design in the multisensory system allows measuring the environment temperature in the range of −60…+300 °C with an accuracy of 0.1–0.01 °C, and the gas concentration in the range of 10…90% with the accuracy of 0.1–0.5%.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

Photovoltaic modules should pass series of tests and examinations, verifying the electrical and thermal characteristics of the module, before being released to the market, examining the properties of the modules should undergo appropriate durability and efficiency tests under real outdoor conditions with exposure to climatic conditions and under laboratory conditions. The performance of photovoltaic cells depends on many factors, such as solar irradiance, module operating temperature, installation location, weather conditions and module shading. In this paper, three selected photovoltaic modules were examined using a large-scale steady-state solar simulator. The current-voltage (I-V) characteristics of the photovoltaic modules were experimentally tested and analyzed. The next step was to implement a three-layer artificial neural network model (MLP). The experimental data obtained in the previous step coupled with output data from MLP were then used in global sensitivity analysis (GSA). Experiments carried out on a large-scale stationary solar simulator showed differences between the values declared by the manufacturer and the values obtained from measurements of PV modules. The first module tested achieved the maximum power point greater than that specified by the manufacturer, while the other two showed power drops; it was 85-87% for the second module, and 95-98% for the third, respectively. The performed global sensitivity analysis (GSA) for the MLP model showed that the parameters: eff (22.9) and Voc/V (14.19) have the largest effect on the power-voltage relationship, while U (7.29) has the smallest effect. The usefulness of machine learning (ML) methods in the comparative analysis of PV modules has been proved.

Composite biomaterials that combine osteoconductive and osteoinductive properties are a promising approach for bone tissue engineering (BTE) since it allows osteogenesis stimulation while mimicking the extracellular matrix (ECM) morphology. In this context, the aim of the present research work was to produce polyvinylpyrrolidone (PVP) nanofibers containing mesoporous bioactive glass (MBG) 80S15 nanoparticles. These composite materials were produced by electrospinning technique. The design of experiments (DOE) was used to estimate the optimal electrospinning parameters to reduce average fiber diameter. The polymeric matrices were thermally crosslinked under different conditions, and the fiber’s morphology was studied using scanning electron microscopy (SEM). Evaluation of the mechanical properties of nanofibrous mats revealed a dependence on thermal crosslinking parameters and on the presence of MBG 80S15 particles inside the polymeric fibers. Degradation tests indicated that the presence of MBG led to a faster degradation of nanofibrous mats. On the other hand, MBG presence also leads to higher swelling capacity. The assessment of in vitro bioactivity in simulated body fluid (SBF) was performed in MBG pellets and PVP/MBG (1:1) composites to assess whether the bioactive properties of MBG 80S15 were kept when it was incorporated into PVP nanofibers. FTIR and XRD analysis along with SEM–EDS results indicated that a hydroxy-carbonate apatite (HCA) layer was formed on the surface of MBG pellets and nanofibrous webs after soaking in SBF over different time periods. In general, the materials revealed no cytotoxic effects on Saos-2 cell line. The overall results for the produced materials show the potential of the composites to be used in BTE.

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

Background Cesarean scar ectopic pregnancies are a rare form of extrauterine pregnancies, yet their incidence has increased along with the rise in the number of cesarean deliveries. As with other ectopic pregnancies, cesarean scar ectopic pregnancies pose a greater risk for maternal hemorrhage and ultimately maternal mortality. Case presentation We present a series of clinical cases of cesarean scar ectopic pregnancy diagnosed by transvaginal ultrasonography. Each patient received an individualized treatment: the rate of success depended on the particular maternal condition in each case. Due to the low frequency of this entity, there are no clear protocols for its treatment and thus there are numerous options for treatment and follow up: expectant management, medical therapy, surgical intervention, uterine artery embolization or a combined approach. Each method has different levels of success and is dependent on the surgeon’s skill and patient presentation. The transvaginal ultrasound is necessary to obtain the fine details of the gestation sac and its relation to the scar and must be followed by a meticulous abdominal scan with a full bladder. Conclusion Herein, we present a rare pathological phenomenon whose frequency is on the rise, and for which transvaginal ultrasound and flow doppler provide high diagnostic accuracy. Early diagnosis of cesarean scar ectopic pregnancies offers treatment options to that may help avoid uterine rupture and bleeding, thus preserving the uterus and future fertility.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

Listerias of the phylogenetic lineage II (PLII) are common in the European environment, and are hypovirulent. Despite this, they caused more than a third of sporadic cases of listeriosis, and multi-country foodborne outbreaks. L. monocytogenes ST37 is one of them. During the COVID-19 pandemic ST37 appeared in the clinical cases and ranked second in occurrence among food isolates in the Moscow region. The aim of this study was to describe the genomic features of ST37 isolates from different sources. All clinical cases of ST37 were in the cohort of male patients (age, 48-81 years) with meningitis-septicemia manifestation, and COVID-19 or Influenza in the anamnesis. The core genomes of the fish isolates were closely related. The clinical and meat isolates revealed a large diversity. Prophages (2-4/genome) were the source of the unique genes. Two clinical isolates displayed the pseudolysogeny, and excided prophages were A006-like. Absence of the plasmids, the assortment of virulence factors and resistance determinants in chromosome corresponded to the hypovirulent characteristics. However, all clinical isolates caused severe disease with deaths in four cases. Thus, these studies allow us to speculate that a previous viral infection increases a human susceptibility to listeriosis.

In this study a material based on Polyethylene (PE) and Microcrystalline Cellulose (MC) was developed as a breathable packaging film. Surface functionalization of MC with 3 aminopropyltriethoxysilane (APTES) shows to be an efficient alternative to tailor their properties and increase opportunities for the application of MC on the reinforcement of polymers such polyethylene (PE). Functionalization of MC with mentioned silane derivative was achieved using a green method and later used on the development of composites with PE in three percentages (1, 3 and 5%). All the materials were prepared by melt blending and characterized, in terms of structural properties (ATR-FTIR and FTIR in transmittance, EDX, SEM), thermal properties (DSC and TGA), thermomechanical properties (DMA), contact angle measurements and permeability to oxygen and water vapor. The materials demonstrated to have potential to be used as breathable film packaging of fresh products.

Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental compo-nents. Globally, in 2019, 18 million people had RA. RA is characterised by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are the most prevalent secondary metabolites in plants, with a diverse spectrum of biological ac-tions that benefit functional meals and nutraceuticals. These compounds have received a lot of at-tention recently because they have antioxidant, anti-inflammatory, immunomodulatory, and anti-rheumatoid activity by modulating tumour necrosis factor, mitogen-activated protein kinase, nu-clear factor kappa-light-chain-enhancer of activated B cells, and c-Jun N-terminal kinases, as well as other preventative properties. This article discusses dietary polyphenols, their pharmacological properties, and innovative delivery technologies for the treatment of RA, with a focus on their possible biological activities. Nonetheless, commercialization of polyphenols may be achievable only after confirming their safety profile and completing successful clinical trials.

Crystalline silver thin layers were obtained by high-energy pulsed laser ablation without heating of the deposition substrate. The fluid Plateau-Rayleigh (PRI), Rayleigh – Taylor (RTI) and Richtmyer – Meshkov (RMI) instabilities, as well as crown splash induced during pulsed laser deposition (PLD) in high energy regime, resulting in ring and pearl shaped structures, offer the benefit of increased sorption surface. These morphological structures obtained for the silver thin layers make them of interest for catalytic applications. The study presented with this work addresses both the fundamental and applied issues on the morphological structures obtained for the silver thin layer and their catalytic function in organic processes. In this sense, the catalytic action of the thin silver layer was highlighted by modifications of the Reactive Blue 21 dye (C.I.) in aqueous solution with sodium bicarbonate. Specific investigations and analyzes were carried out by electron microscopy and elemental analysis (SEM-EDX), atomic force microscopy (AFM) and profilometry, mass spectrometry, ablation plasma diagnosis, diffractograms (XRD), as well as IR spectroscopy (FTIR). In addition to the experimental investigation and analyzes, simulation of the ionization energy threshold was conducted in COMSOL for complementary evaluation on the involved processes and phenomena.

Coconut is an important multipurpose crop wherein different stages of its maturity are used for different products. Traditional approach of its classification use sound formed by tapping the fruit, and the tapper will base its judgment through the sound he heard. The procedure was highly subjective and attempts had been made by other researchers to automate and classify the adulthood of the coconut objectively. Nowadays, deep learning techniques are being utilized to solve classification problems. One such method is Convolutional Neural Network (CNN) that takes raw pixel data, learns to extract features, and ultimately classifies the input. In this study, a portable device was developed that takes audio signals generated from tapping the fruit mechanically. This audio clip was converted to spectrogram and was used as input to a LeNet CNN architecture. We argue that CNN classifier has improved accuracy compared to the non-deep learning system. Our evaluation confirmed that the use of CNN had improved the accuracy of classifying coconut by about 15%.

Many studies have been conducted using pectin for modified drug delivery. In this regard, the goal of the work was to obtain interpolyelectrolyte complexes based on citrus or apple pectin and the Eudragit® EPO and study properties from the standpoint of using these carriers for oral drug delivery. Turbidity, gravimetry, viscosity, elementary analysis and FTIR spectroscopy, DSC analysis were used for physicochemical characterization. Diffusion-transport characteristics were studied to assess the swelling ability of the matrices and the release of diclofenac sodium. Mathematical modeling of the release parameters was carried out using the Krosmayer-Peppas equation. During the turbidity study, stoichiometry compositions were selected for the studied IPECs EPO/PeсA and EPO/PeсC at pH values = 4.0, 5.0, 6.0, 7.0. FTIR spectra of the complexes are characterized by an increase in the intensity of the bands at 1610 cm-1 and 1400 cm-1. According to the DSC analysis IPEC has a certain Tg = 57.3°C. The highest release rates are shown by IPEC EPO/PecC_1 and EPO/PecC_4. The mechanism of drug transport from the matrices IPEC EPO/PecC, IPEC EPO/PecA_3 and EPO/PecA_4 can be characterized as Super Case II. Anomalous (non-Fickian release) is typical for IPEC EPO/PecA_1 and EPO/PecA_2. Thus, the resulting systems are suitable for colon-specific drug delivery systems.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

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

The compatibility between the de Sitter Swampland conjecture and Ho\v{r}ava-Lifshitz $F(\bar{R})$ theories with a flat FLRW metric is studied. We first study the standard $f(R)$ theories and show that the only way in which the dS conjecture can be made independent of $R$ is by considering a power law of the form $f(R)\sim R^{\gamma}$. The conjecture and the consistency of the theory puts restrictions on $\gamma$ to be greater but close to $1$. For the $F(\bar{R})$ theories described by its two parameters $\lambda$ and $\mu$ we use the equations of motion to construct the function starting with an ansatz for the scale factor in the Jordan frame of the power law form. By doing a conformal transformation on the three metric to the Einstein frame we can obtain an action of gravity plus a scalar filed by relating the parameters of the theory. The non-projectable and projectable cases are studied and the differences are outlined. The $F(\bar{R})$ function obtained consists of terms of the form $\bar{R}^{\gamma}$ with the possibility of having negative power terms. The dS conjecture leads to inequalities for the $\lambda$ parameter, in both versions it gets restricted to be greater but close to $1/3$. For the general case in which $\mu$ and $\lambda$ are considered as independent, the action contains an extra term but we propose that the conjecture is still applicable. Once again the non-projectable and projectable cases are studied. The $F$ function obtained has the same form as before, the consistency of the theory and the dS conjecture lead to a set of inequalities on both parameters that are studied numerically. In all cases $\lambda$ is restricted by $\mu$ around $1/3$ and we obtain $\lambda\to1/3$ if $\mu\to0$. Finally we consider the $f(R)$ limit $\mu,\lambda\to1$ and we obtain consistent results.

In this work, we explore a the different forms of a new type of modified gravity, namely f(φ) gravity. We construct the Big Rip type for the energy density and the curvature of the universe. We show that dark energy is a result of the transformation of the field φ mass (dark matter) to energy. In addition, we provide that Ω_{m}≈0,050, Ω_{DM}≈0,2, Ω_{DE}≈0,746, is in excellent agreement with observation data. We explore a generalized formalism of braneworld modified gravity. We also construct a new field equations, which generalize the Einstein field equations. We provide a relation between the extra dimension in 3-brane with the vacuum energy density. We show that the energy density of matter depends directly on the number of dimensions. We manage to find the value of the Gauss-Bonnet coupling α=1/4 which is a good agreement with the results in the literature, this correspondence creates a passage between f(R) gravity and Gauss-Bonnet gravity, this comparison leads to a number of bulk dimensions equal to D=10¹²¹+4.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

Despite polycarbonate (PC) being a widely used engineering plastic, its notch and crack sensitivity pose challenges in critical applications. To address this, PC was blended with elastomeric polymers to explore the improvement in toughness. This study systematically investigates the toughening mechanisms of PC blended with acrylonitrile-butadiene-styrene (ABS), copolyether ester elas-tomer (COPE), and ABS and styrene-ethylene-butylene-styrene (SEBS) copolymer grafted with maleic anhydride (MA). The morphology and mechanical behavior were evaluated under qua-si-static and high-speed tensile tests and Charpy impact tests using optical, electronic, and atomic force microscopy and Raman spectroscopy. The morphological analysis reveals cavitation and crazing phenomena for COPE and SEBS-g-MA systems, and mostly debonding for ABS, indicating an improvement in toughening. While the addition of ABS improves the PC plastic deformation, modifying ABS with maleic anhydride enhances the elastic modulus. Blending PC with SEBS-g-MA increases the strain at break, and the addition of COPE significantly improves the deformation behavior of PC (by around 115%). This comparative study provides valuable insights into the performance of different PC-elastomer blends under similar conditions, supporting the selection of appropriate materials for given applications.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

CAMx-LPiG (Comprehensive Air Quality Model with Extensions – Linear Plume in Grid) is an online hybrid model, based on the Chemistry and Transport Model (CTM) CAMx, that includes a sub-grid scale module to simulate the dispersion of linear road traffic emissions, called LPiG. LPiG is a plume in grid module specifically developed by extending the capabilities of the Lagrangian puff sub-grid model available in CAMx. The online integration of the local scale model within the Eulerian CTM allows for a multiscale simulation of air quality from the regional scale to the urban scale, preserving a coherent description of the chemical state of the atmosphere at all spatial scales and avoiding any double counting of the emissions simulated by the sub-grid module. In this work the model is presented and evaluated against measured NO2 concentrations for the city of Milan for the month of January 2017. The model is able to introduce road traffic induced gradient in NO2 concentration at sub-grid resolution. Moreover, CAMx-LPiG is shown to reduce the bias compared to CAMx stand-alone simulations.

Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. PCL based scaffolds are fairly applied for bone regeneration, and several composites have been incorporated, as to improve the devices’ mechanical properties and tissue ingrowth. In this study, HA was incorporated on PCL based scaffolds with two different proportions, 80:20 and 60:40. Devices were produced with two different techniques, SC and MB, and further investigated with regards to their mechanical characteristics and in vitro cytocompatibility. Results show the MB devices to present more promising mechanical properties, along with the incorporation of HA. The latter is also related to an increase in osteogenic activity and promotion. Overall, this study suggest PCL:HA scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the MB method.

Drosophila melanogaster serves as a important research model both for genetic investigations and for the study of metal toxicity, facilitating the elucidation of physiological mechanisms comparable to those of human organisms. In our research, we evaluated the toxicity effect resulting from exposure to various concentrations of lead and copper on the prolificity rates throughout the life cycle (egg-adult) of four genotypes of Drosophila melanogaster: wild-type (control), white, brown, and white-vestigial. During our study, the prolificity rates were examined across three repetitions under the impact of exposure to concentrations of 0.50, 1.00, 2.00, and 4.00 mM of copper (CuSO₄) and lead (Pb(C₂H₃O₂₎₂). Prolificity rates throughout the life cycle exhibited variations as a direct consequence of genetic factors, the concentration of exposure, and the specific type of metal, either copper or lead. The mutant white-vestigial genotype revealed an IC₅₀ concentration for prolificity inhibition at lower doses of 2.00 mM for copper and 4.00 mM for lead, in contrast to the control genotype (wild-type), which exhibited an inhibition concentration rate >IC₅₀ of 4.00 mM only in the case of copper. Our results concluded that the (i) dose influences the prolificity rate in a directly proportional manner, (ii) comparative analyses between copper and lead revealed that copper displayed toxicity across all genotypes within the concentration range of 0.50 mM to 2.00 mM. In contrast, lead exhibited toxicity within the concentration range of 1.00 mM to 4.00 mM, highlighting a (iii) more acute toxicity characteristic in the case of copper. Thus, the results of this research reflect the importance of using Drosophila melanogaster as a genetic model in the comparative study of the interaction between genetic factors and the toxicity of metals, offering significant insights into monitoring their impact and defining the maximum permissible doses on organisms.

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Organisms are adapted to each other and the environment, not as tradition would have it, because natural selection made them that way, but because there is inbuilt striving towards stability and equilibrium. A General Theory of Behaviour connects imagery, affect and action with the central executive system we call Consciousness. The General Theory is founded on the assumption that the primary motivation of all of Consciousness and intentional behaviour is Psychological Homeostasis. Psychological homeostasis is as important to the organisation of mind and behaviour as Physiological Homeostasis is to the organisation of bodily systems. Consciousness processes quasi-perceptual images independently of the input to the retina and sensorium. Consciousness is the “I-Am” control centre for integration and regulation of (my) thoughts, (my) feelings and (my) actions with (my) conscious mental imagery as foundation stones. Imagery vividness, a combination of clarity and liveliness, is essential to imagining, remembering, thinking, predicting, planning and acting. Assessment of vividness using introspective report is validated by objective means such as fMRI. A significant body of work shows that vividness of visual imagery is determined by the similarity of neural responses in imagery to those occurring in perception of actual objects and performance of activities. I am Conscious, therefore I am.

In this paper, we present a three-step sixth-order iterative schemes to estimate the solutions of a nonlinear systems of equations, for predicting the shear strength of a reinforced concrete beam. This procedure is designed by means of a weight function technique. The values for the parameters of this system were randomly selected inside the prescribed ranges by technical standards for structural concrete; moreover, some of this parameters were fixed taking into consideration the solvability region of the adopted steel constitutive model. The efficiency of the new class is compared with other current schemes, with very good results.

A wealth of Full Waveform (FW) LiDAR data are available to the public from different sources, which is poised to boost the extensive application of FW LiDAR data. However, we lack a handy and open source tool that can be used by potential users for processing and analyzing FW LiDAR data. To this end, we introduce waveformlidar, an R package dedicated to FW LiDAR processing, analysis and visualization as a solution to the constraint. Specifically, this package provides several commonly used waveform processing methods such as Gaussian, adaptive Gaussian and Weibull decompositions, and deconvolution approaches (Gold and Richard-Lucy (RL)) with users’ customized settings. In addition, we also developed functions to derive commonly used waveform metrics for characterizing vegetation structure. Moreover, a new way to directly visualize FW LiDAR data is developed through converting waveforms into points to form the Hyper Point cloud (HPC), which can be easily adopted and subsequently analyzed with existing discrete-return LiDAR processing tools such as LAStools and FUSION. Basic explorations of the HPC such as 3D voxelization of the HPC and conversion from original waveforms to composite waveforms are also available in this package. All of these functions are developed based on small-footprint FW LiDAR data, but they can be easily transplanted to the large footprint FW LiDAR data such as Geoscience Laser Altimeter System (GLAS) and Global Ecosystem Dynamics Investigation (GEDI) data analysis. It is anticipated that these functions will facilitate the widespread use of FW LiDAR and be beneficial for better estimating biomass and characterizing vegetation structure at various scales. The package and code examples can be found at https://github.com/tankwin08/waveformlidar.