The regulation of multiple bacterial phenotypes was found to depend on different cyclic di-nucleotides (CDNs) that constitute intracellular signalling second messenger systems. Most notably, c-di-GMP, along with proteins related to its synthesis, sensing and degradation, was identified as playing a central role in the switching from biofilm to planktonic modes of growth. Recently, this world has been under expansion, with the discoveries of other signalling CNDs in bacteria (c-di-AMP and cGAMP) and also in eukaryotes, novel protein and RNA receptors of CDNs, and the numerous functions related to these molecules. In this work, we comprehensively review and analyse the structural biology data about the systems that bacteria use to synthesise and recognise CDNs, detailing their interactions at molecular level with their products/ligands. Additional interesting observations were made, including that different receptor types can bind CDNs in similar conformations and that, based on genomic data, different CDN second messenger systems may coexist in many organisms. The large amount of sequence and structural data available allows a broad view of the importance of CDNs in bacteria, but how cells coordinate these molecules to ensure adaptation to changing environmental conditions is still open for much further exploration.

As participating molecules in nucleic acids, nucleotides also have signaling functions and act as second messengers in both prokaryotic and eukaryotic cells, the most common example being cyclic AMP (cAMP). In bacteria, a great interest has arisen in studying nucleotide signaling. It has been determined that cyclic di-AMP (c-di-AMP), cAMP, and cyclic di-GMP (c-di-GMP) participate in biological events such as bacterial growth, biofilm formation, sporulation, cell differentiation, motility, virulence, and other. Moreover, these cyclic-di-nucleotides (c-di-nucleotides) produced in pathogenic intracellular bacteria can affect eukaryotic host cells for infection. On the other hand, the nucleotide molecules pppGpp, and ppGpp are alarmones involved in regulating bacterial nutritional stress; they are also considered second messengers. These second messengers can be used as therapeutic agents because of their immunological functions on eukaryotic cells. In this review, different topics on the role of c-di-nucleotides as second messengers in different bacterial processes are addressed.

The toxin-antitoxin (TA) systems have been attracting attention due to their role in regulating prokaryotic cell responses to stress and their biotechnological potential. Much recognition has been given to type II TA system of mesophiles, but so far, limited attention has been given to thermophiles. Here, we are presenting the putative type II TA families encoded on the genomes of four Geobacillus strains. We employed the TA finder tool to mine for TA-coding genes and manually curated the results using various tools. We identified 28 putative TA pairs, distributed over 8 TA families. Among the identified TAs, 15 represent putative novel toxins and antitoxins that have been overlooked or annotated as hypothetical proteins in their genome records. We also identified a potentially new TA composite, AbrB-ParE. Furthermore, we are suggesting the Geobacillus acetyltransferase toxin-antitoxin (GacTA) family which potentially represents one of the unique TA families that has a reverse gene order. Moreover, we are proposing a hypothesis on the regulation of the xre-cog2856 gene expression, which seems to involve c-di-AMP. This study aims for highlighting the significance of studying TAs in Geobacillus, since they have special features. It also aims for facilitating future experimental research.

Cadmium is a highly toxic heavy metal for biological systems. Cupriavidus metallidurans CH34 is a model strain for heavy metal resistance and bioremediation. The aim of this study was to determine the role of the c-di-GMP pathway in the C. metallidurans CH34 response to cadmium in both planktonic and biofilm cells. Increasing cadmium concentrations correlates with an inhibition of biofilm formation and EPS production in C. metallidurans cells. Planktonic and biofilm cells showed similar tolerance to cadmium. During exposure to cadmium an acute decrease of c-di-GMP levels in planktonic and biofilm cells was observed. Transcription analysis by RT-qPCR showed that cadmium induced in planktonic cells and strongly induced in biofilm cells the expression of the urf2 gene and the mercuric reductase encoding merA gene, which belong to the Tn501/Tn21 mer operon. After exposure to cadmium the cadA gene involved in cadmium resistance was equally upregulated in both lifestyles. Bioinformatic analysis and null mutant complementation assays indicated that the protein encoded by the urf2 gene is a functional phosphodiesterase involved in the c-di-GMP metabolism. We propose to rename the urf2 gene as mrp gene for metal regulated phosphodiesterase. An increase of the second messenger c-di-GMP content by the heterologous expression of the constitutively active diguanylate cyclase PleD* correlated with an increase in biofilm formation and cadmium susceptibility. These results indicate that the response to cadmium in C. metallidurans CH34 involves a decrease in c-di-GMP content that inhibits the biofilm lifestyle.

In this paper, several two-dimensional clustering scenarios are given. In those scenarios, soft partitioning clustering algorithms (Fuzzy C-means (FCM) and Possibilistic c-means (PCM)) are applied. Afterward, VAT is used to investigate the clustering tendency visually, and then in order of checking cluster validation, three types of indices (e.g., PC, DI, and DBI) were used. After observing the clustering algorithms, it was evident that each of them has its limitations; however, PCM is more robust to noise than FCM as in case of FCM a noise point has to be considered as a member of any of the cluster.

The advent of social commerce (SC) has transformed the landscape of online consumer behavior, emphasizing the significance of customer-to-customer relations in shaping sustainable relation-ships with customers. This research investigated the intricate relationships between social com-merce dimensions, particularly suggestions and recommendations, forums and communities, and ratings and reviews, and their influence on customer-to-customer value co-creation (C2CVCC) and sustainable customer relationships (SCRs). A questionnaire was designed and administered to 635 respondents. We examined the psychometric properties of the measurements and subse-quently applied Partial Least Squares as a Structural Equation Modeling method (PLS-SEM) for hypothesis testing. The findings reveal that the dimensions of SC significantly impact C2CVCC, with ratings and reviews playing a pivotal role. Furthermore, C2CVCC emerges as a substantial mediator in the path between SC and SCRs. The empirical analysis showcases strong support for the proposed model, with robust path coefficients (β) and p-values confirming direct and indirect effects. These findings offer valuable insights for businesses seeking to leverage SC and customer interactions to enhance SCRs in the digital era. Understanding the dynamics of C2CVCC within the context of SC has become essential for marketers and businesses aiming to thrive in today's competitive online marketplace.

Owing to their extensive biological potential, essential oils (EOs) and their bioactive phytochemicals have gained attention from the scientific community. Within this domain, Terpinen-4-ol (T-4-ol), a bioactive monoterpene alcohol and the major constituent of tea tree oil (TTO), has made its way into translational research. Recent literature on T-4-ol strongly indicates its diverse pharmacological properties, including but not limited to antimicrobial, antivirulent, antioxidant, anti-inflammatory, anti-hypertensive, and anti-cancer effects. Hence, this review provides a comprehensive overview of the multifaceted biological activities exhibited by T-4-ol, emphasizing its medicinal potential for widescale application. The antibacterial and antifungal effectiveness of T-4-ol has been discussed encompassing its role in combating a broad spectrum of bacterial and fungal pathogens, respectively. The review delves into the antivirulent prospects of T-4-ol, shedding light on its ability to attenuate virulence and mitigate bacterial pathogenesis. Scientific literature on the antioxidant and anti-inflammatory activity of T-4-ol highlighting its role in neutralizing reactive oxygen species and modulating inflammatory pathways has also been collated. Furthermore, the review elaborates on the cardioprotective and anti-hypertensive properties of T-4-ol and augments literature on its anti-cancer mechanism against various cancer cell lines. Overall, this review consolidates the existing knowledge on T-4-ol, providing a holistic understanding of its pharmacological abilities. The exploration of these diverse attributes positions T-4-ol as a promising candidate for further research and therapeutic repurposing in various biomedical applications.

The rise of antibiotic-resistant strains of clinically important pathogens is a major threat to global health security. The World Health Organization (WHO) has recognized the urgent need to develop alternative treatments to address the growing list of priority pathogens. Antimicrobial peptides (AMPs) rank among the various suggested options with proven activity and a high potential to be developed into effective agents. Many AMPs are naturally produced by living organisms and protect the host against pathogens as a part of their innate immunity. Various mechanisms associated with their antimicrobial actions include cell membrane disruption, cell wall weakening, protein synthesis inhibition, and interference in nucleic acid dynamics that can induce apoptosis and necrosis. Acinetobacter baumannii is considered a critical pathogen, and severe clinical problems have appeared with isolates resistant to current antibiotic treatments and conventional control procedures such as UV light, disinfectants, and drying. Here, we review the natural AMPs representing the primary candidates for new anti-A. baumannii drugs in a post-antibiotic era and present the use of computational tools to develop the next generation of AMPs with greater microbicidal activity and reduced toxicity.

The supposition is that the usage of fibrin rich in leukocytes and platelets advanced (A-PRF) in ulcerative osteomyelitis of the diabetic foot allows rehabilitation from this critical illness. In this investigation, the focus was to normalize the use of PRF in patients with osteomyelitis not amputated, to use this second generation platelet concentrate as a regeneration enabler. The researchers submitted and utilized A-PRF membranes (1300 g × 8 min) in 7 patients (all diabetics) with osteomyelitis and cutaneous injury for 6 months. The membranes, in combination with the supernatant fluid produced by stress, have been integrated into the skin lesion down to the bone after surgical debridement. The advancement of the lesions after some period of time has been analyzed. All seven subjects had a Probe-to-Bone positive assay; MRI indicated a cortico-periosteal coagulation and/or foci of cortico-spongeous osteolysis contiguous to the lesion. Gram-positive bacterium were identified in our procedures in 52% of cases. Gram+ Cocci, for example, S. Aureus (15.6%), S. Hemolytic (12.1%), S. Viridans (7.1%), and Gram-negative Bacteria, for example, Pseudomonas (10.6%), Proteus (7.8%), Enterobacter (5.7%) are present. Candida Albicans is active in 2.8%. The blood count shows no relevant differences. To date, cutaneous lesions have cured in 6 of the seven subjects treated (one patient for more than five years) without any evidence of infection or recurrence. The results obtained on our subjects indicate that PRF membranes may be a therapeutic option in this problematic disease.

Antimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative E. coli and AMPs is driven by lipopolysaccharides (LPS) that act as kinetic barriers for the binding of AMPs to the bacterial membrane. A combination of SPR and NMR experiments provide evidence suggesting that cationic AMPs first bind to the negatively charged LPS before reaching a binding place in the lipid bilayer. In the event that the initial LPS-binding is too strong (corresponding to a low dissociation rate), the cationic AMPs cannot effectively get from the LPS to the membrane and their antimicrobial potency will thus be diminished. On the other hand, the AMPs must also be able to effectively interact with the membrane to exert its activity. The ability of the studied cyclic hexapeptides to bind LPS and to translocate into a lipid membrane is related to the nature of the cationic charge (arginine vs lysine) and to the distribution of hydrophobicity along the molecule (alternating vs clumped tryptophan).

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

The last 20 years have seen significant advancements in polymeric drug delivery methods. A formulation or a system that makes it possible for a medicinal ingredient to be injected into the body is known as polymeric drug delivery1. The key choice for many novel medication delivery methods is made achievable by biodegradable and bio-reducible polymers. The research's prospects for practical applications have necessitated the field's development—the choice for a lot of new drug delivery systems. The prospects of the research for practical applications are required for the development in the field. Polymeric drug delivery methods have been developed from natural polymers like arginine, chitosan2, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid. Regarding polymeric drug delivery1, synthetic polymers such as poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable, and bioabsorbable polymers have all been considered. Polymeric drug delivery has also been addressed by focusing on drug-free macromolecular therapies, biomimetic and bio-related polymeric systems, and targeting polymeric drug delivery. Pharmaceutical fields are seeing a tremendous rise in the development of polymeric drug delivery methods based on natural and manmade polymers. The successful advancements in the utilization of biocompatible and bio-related copolymers and dendrimers in cancer treatment, including their application as vehicle systems for highly effective anticancer medications3. A new paradigm for the development of polymeric drug and gene delivery systems will be possible through the fusion of viewpoints from the synthetic and biological domains.

Fungal-bacterial co-colonization and co-infections are emerging among TB-suspected patients, yet the underlying mechanisms that enable and arise from their interactions are poorly understood. Understanding how environmental microbes such as fungi and bacteria co-evolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic co-infections. Our previous work has demonstrated that fungal-bacterial interactions can have dramatic impacts on fungal pathogenesis and drug resistance. Here, we, therefore, hypothesize that cross-kingdom synergistic interactions between environmental fungi and bacteria may influence both fungal and bacterial virulence, antimicrobial resistance patterns and aetiology. Through this, we aimed to establish the prevalence of fungal–bacterial microbial communities associated with chronic primary or opportunistic pulmonary infections. Concordantly, through surveilling 302 clinical samples from 151 patients, we established the prevalence of TB (0.7%) to be lower than that of fungi (1.3%) and non-TB bacterial (4.6%) mono-aetiologies Figure 2. However, our main observation was the unexpected taxonomic diversity with a striking twist of fungal-bacterial di-kingdom aetiological conformities. Interestingly, the majority of the patients presented with at least a di or mono-kingdom aetiological pairings. Importantly, fungi and non-TB bacteria formerly regarded as atypical opportunists are now frequently isolated as possible aetiology for chronic pulmonary infection. Hence, we revealed many di-kingdom aetiological pairings here but their significance remains a question of further examination. Among which Acremonium spp + K. pneumoniae (n=5), Acremonium spp +Streptococcus pneumoniae (n=4), Acremonium spp + C. albicans + K. pneumoniae (n=3) were among the most dominant aetiological pairings observed. Interestingly, Acremonium spp + K. pneumoniae pairings were also seen to be the most commonly associated with pulmonary TB both during and after treatment. Isolation from the same infection niche as seen here calls for further investigations into any interaction signatures that may exist between these organisms. Taken together, our data suggest that fungal-bacterial co-existence may influence their virulence attributes and antimicrobial resistance patterns, with relevance to patient outcomes. Therefore, our data reveals an array of fungal-bacterial pairings that may influence the prognosis of chronic pulmonary disease. Importantly, suggesting that the diversity of pulmonary infective fungi and bacteria, and their complex population structures may pose challenges to the analysis and interpretation of conventional data. Thus, there is a need to redirect our diagnostic approaches to encompass polymicrobial aetiology in order to enhance our suspicion index for better management of opportunistic fungal-bacterial co-infections.

Engineering Education needs to be approached in different, innovative ways to meet the needs of society, learners, and education providers. This ranges from new educational programs and innovative pedagogies in individual classrooms, to online and immersive learning, to micro-credentials and modularity along with how to enable rapid adaptation for reskilling and upskilling, to entirely new pathways of restructuring education. Gamification is the application of game elements and digital game design techniques to non-game problems, such as learning challenges. It is about using game-based mechanics, aesthetics, and game thinking to enhance users’ engagement, motivate action, and support learning. At first view, the concept of gamification does not contain game design elements, but with the addition of additional elements such as the video game component that is applied in different contexts, the users are encouraged to participate in learning activities and complete learning challenges successfully. The first step in the process of designing a gamification activity is to think like a game designer. According to Cook (2013), any process can be gamified when the following requirements are covered: (i) the gamified activity is easy to learn, (ii) user progress can be measured, (iii) continuous feedback is provided to users.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

Sleep fragmentation (SF) can increase inflammation and production of reactive oxygen species (ROS), leading to metabolic dysfunction. SF is associated with inflammation of adipose tissue and insulin resistance. Several studies suggested that melatonin may have beneficial metabolic effects by activating AMP-activated protein kinase (AMPK). However, it is unclear whether melatonin affects the AMPK signaling pathway in SF-induced metabolic dysfunction. Therefore, we hypothesize that SF induces metabolic impairment and inflammation in white adipose tissue (WAT), as well as altered intracellular homeostasis. We further hypothesize that these conditions could be improved by melatonin treatment. We conducted an experiment using adult male C57BL/6 mice, which were divided into three groups: control, SF, and SF with melatonin treatment (SF+Mel). The SF mice were housed in SF chambers, while the SF+Mel mice received daily oral melatonin. After 12 weeks, glucose tolerance test, insulin tolerance test, adipose tissue inflammation, and AMPK assessments were performed. The SF mice showed increased weight gain, impaired glucose regulation, inflammation, and decreased AMPK in WAT compared to the controls. Melatonin significantly improved these outcomes by mitigating SF-induced metabolic dysfunction, inflammation, and AMPK downregulation in adipose tissue. The therapeutic efficacy of melatonin against cardiometabolic impairments in SF may be due to its ability to restore adipose tissue homeostatic pathways.

It is at the chemistry-biology interface that this work that we have carried out takes place. Indeed, the expected goal is to develop simple molecules, capable of activating the catalytic action of certain metalloenzymes such as tyrosinase. The official name of an enzyme includes the type of reaction catalyzed, the name of the substrates involved. In this work, we carried out the study of the catalytic activity of the complexes of organotin carboxylates synthesized vis-à-vis the oxidation of 3,5-di-tert-butylcatecchol. The results obtained show that the various complexes exhibit good catalytic activity for the oxidation of 3,5-di-tert-butylcatecchol under mild conditions. The complexes that showed good catalytic activity are the compounds C1 and C2.

Higher body weight is known to negatively impact plasma vitamin C status. However, despite this well-documented inverse association, recommendations on daily vitamin C intakes by health authorities worldwide do not include particular reference values for people of higher body weight. This suggests that people of higher body weight and people with obesity may be insufficient in vitamin C in spite of ingesting the amounts recommended by their health authorities. The current preliminary investigation sought to estimate how much additional vitamin C people with higher body weights need to consume in order to attain a comparable vitamin C status to that of a lower weight person consuming an average Western vitamin C intake. Data from two published vitamin C dose-concentration studies were used to generate the relationship: a detailed pharmacokinetic study with seven healthy non-smoking men and a multiple depletion-repletion study with 68 healthy non-smoking men of varying body weights. Our estimates suggest that an additional intake of 10 mg vitamin C/day is required for every 10 kg increase in body weight to attain a comparable plasma concentration to a 60 kg individual with a vitamin C intake of ~110 mg/day, which is the daily intake recommended by the European Food Safety Authority (EFSA). Thus, individuals weighing e.g. 80 and 90 kg will need to consume ~130 and 140 mg vitamin C/day, respectively. People with obesity will likely need even higher vitamin C intakes. As poor vitamin C status is associated with increased risk of several chronic diseases including cardiovascular disease, these findings may have important public health implications. As such, dose-finding studies are required to determine optimal vitamin C intakes for overweight and obese people.

The significance of Kashmir conflict as one of the world’s longest running conflicts has frequently drawn the attention of both communication and international relations’ scholars which makes it an important issue from the perspective of interdisciplinary approach. The researchers have attempted to assemble a brief history of the Indian held Jammu and Kashmir Conflict from the time of partition in 1947 to the developments which took place till 2019 in the light of the available literature. The paper provides substantial historical context of the important events like instrument of accession, UN resolutions on Kashmir conflict, Simla Accord, Gawkadal Massacre , Lahore Declaration, Kargil War, killing of Burhan Wani, Uri attack and Article 370’s abrogation .

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

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

This comprehensive statement explores the concept of educational excellence, emphasizing the limitations of traditional metrics and proposing a holistic model for excellent educational systems. The discussion delves into the ambiguity surrounding excellence, challenges in measurement, and the influence of social, cultural, and economic factors on education. The objectives of the study include shedding light on the nature of excellence, its global significance, and introducing a model for improving school performance. The theoretical framework integrates constructivism, Maslow's Hierarchy of Needs, and Ecological Systems Theory to emphasize student-centered learning, holistic development, and environmental factors. The proposed model envisions an educational ecosystem prioritizing personalized, inclusive, and relevant education, with key components such as student-centered learning, inspirational educators, curriculum innovation, and community involvement. The abstract concludes by highlighting the model's potential implications in transforming education, challenging the status quo, and fostering well-rounded individuals equipped for a rapidly changing world.

This study investigated whether export performance is correlated with innovation. We explicitly considered five types of innovation: a) process innovation; b) product innovation; c) process and product innovation; d) product innovation new to the firm; and e) product innovation new to the market. We en-larged the findings of R&D-export and R&D-investment relations using a vast sample of cross-European firms. We considered innovation as endogenous and determined by R&D through a process characterized by the role of the regional technological environment. Our analysis enabled us to propose an integrated model incorporating R&D, innovation and export, in a framework of simultaneous equations which consider their mutual correlations. To the best of our knowledge, this work is the first in recent years to empirically compute the relation between R&D and tangible investment at the micro level. Econometric results showed that product and process innovation are positively linked to the export intensity of European manufacturing firms. The results also showed complementarity effects between the two kinds of innovation. The av-erage effect on export intensity from carrying out process innovation is larger than that found for product innovation, except in cases where the product is new to the market. When both types of innovation have been carried out, a larger effect results than that found for product or process innovation alone. Furthermore, the average marginal effect on export intensity from innovations of any kind among those studied here is highly positive and significant.

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). ω3-Polyunsaturated fatty acids (ω3-PUFAs) show protective effects against various renal injuries. It was recently reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI. Renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of LC3, Beclin-1, and Atg7; lower amounts of p62; and higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

A solution is presented that describes a region of space, box or warp bubble, where time gets slowed down by an arbitrary factor, while reducing the components of the energy-impulse tensor by any chosen amount.

Biofilm formation is important in the free-living and symbiotic lifestyles of Sinorhizobium meliloti. Here we show that the S. meliloti NspS-MbaA system is homologous to the c-di-GMP modulating NspS-MbaA system described in Vibrio cholerae and modulates biofilm formation, exopolysaccharide (EPS) production and motility in S. meliloti in response to exogenous polyamines. Biofilm and EPS production in quorum sensing-deficient wild type strain 1021 decreased in cultures containing putrescine, 1,3-diaminopropane or spermine, but were unaffected in a 1021 nspS mutant (1021 nspS). Decreases in biofilm formation caused by these polyamines paralleled decreases in EPS production and increases in nspS transcription. Cell aggregation did not differ markedly between strain 1021 and 1021 nspS. The S. meliloti quorum sensing-proficient Rm8530 wild type strain and nspS mutant (Rm8530 nspS) produced similar levels of biofilm under control conditions and 3.2- and 2.2-fold more biofilm in cultures with norspermidine, but these changes did not correlate with EPS production. Rm8530 nspS aggregated up to several fold more than the wild type under most conditions. Changes caused by polyamines in swimming and swarming motility were not generally dependent on NspS-MbaA in either 1021 or Rm8530. We speculate that the S. meliloti NspS-MbaA system could modulate biofilm formation in response to environmental polyamines.

In light of the globally increasing prevalence of diet-related non-communicable diseases (NCDs), new scalable and non-invasive dietary monitoring techniques are urgently needed. Automatically collected digital receipts from loyalty cards have the potential to serve as an objective and automatically traceable digital biomarker for individual food choice behavior and do not require patients to manually log each individual meal item. Until recently, such electronic purchase records were hard to collect for researchers and were only validated in national empirical studies. Multiple quantitative indicators for purchase quality have been suggested, but so far no comparison has validated the potential of these alternative indicators to discriminate between health-beneficial and -detrimental food choices. With the introduction of the General Data Privacy Regulation in the European Union, millions of consumers gained the right to access their purchase data in a machine-readable form, representing a historic chance to leverage purchase data for scalable monitoring of food choices. This study hence is the first study comparing the calibration capacity and validating the discrimination potential of previously suggested purchase indicators for the nutritional quality of purchased groceries, incl. HEI-2015, HETI, GPQI, and FSA-NPS DI. To assess the indicators' potential, 464 study participants were asked to complete a validated food frequency questionnaire (FFQ) and to donate their digital receipts from the loyalty card programs of the two leading Swiss grocery retailers, representing 69\% of the national grocery market. 89 participants fulfilled the eligibility criteria, i.e. completed the FFQ and were frequent users of the loyalty card systems. Compared to absolute food and nutrient intake, correlations between density-based relative food and nutrient intake and food purchase data are stronger. Counterintuitively, although the frameworks of the HETI and the GPQI are centered around food groups, both indicators do not capture food group intake such as vegetables or sweets very well. The FSA-NPS DI has the best calibration and discrimination performance in classifying participants' consumption of nutrients and food groups, and seems to be a superior indicator to estimate nutritional quality of a user's diet based on digital receipts from grocery purchases in Switzerland.

We investigate the value distribution of dierence polynomials of entire and meromorphic functions, which can be viewed as the Hayman's conjecture. And we also study the uniqueness of dierence polynomials sharing a common value.

IHepatitis C virus (HCV) has a high genetic diversity, with seven genotypes with 86 subtypes. This genetic variability confers persistence in the infection and escape of the immune system with evolution to cirrhosis and cancer. Environmental factors can contribute to different disease progression, being essential to assess the viral genotype in the infection and discuss the environmental particularities of Eastern Amazon, and the frequencies of Liver fibrosis between different HCV genotypes in patients living in a region of the Brazilian Eastern Brazilian Amazon. Consists in an observational cross-sectional study. Sociodemographic and clinical data of 76 individuals diagnosed with Hepatitis C between 2019 and 2020 in public health services were selected. Data collected was tabulated in Microsoft Excel 2010TM spreadsheets and analysed in GraphPad Prism 5.0TM. Liver fibrosis was associated with genetic subtypes. Subtype 1b was predominant (42.1%), followed by 1a (13%) and 3a (1.3%). 69.7% of participants had chronic hepatitis, with mild fibrosis (F1/F2) being the most prevalent (38.1%). Severe fibrosis was detected in 75% of individuals infected with the subtype 1b, that is associated with more severe disease. We suggest further studies, to assess other communities in the region, as well as the monitoring of these patients with Liver Elastography to determine the disease evolution and its better management.

This work demonstrates that a plasmid can function as an efficient biocatalyst in mediating the nitroaldol (Henry) reaction at high temperatures in ultrapure water. Compared with ssDNA, the plasmid displayed a remarkable catalytic efficiency (97% yield within 20 min). Aromatic aldehydes which bear strong or moderate electron-withdrawing groups reacted satisfactorily with nitromethane, which afforded the corresponding β-nitroalcohols in good yields within 2 h (up to 98%). By contrast, aliphatic and aromatic aldehydes with electron-donating groups did not react. Moreover, the yield significantly dropped when the size of the carbanion increased, and the yield was only 10% when nitropropane was used as the donor.

The ability to simulate realistically the electronic structure of superconducting materials is important to understand and predict various properties emerging in both the superconducting topological and spintronics realms. We introduce a tight-binding implementation of the Bogoliubov-de Gennes method, parameterized from density functional theory, which we utilize to explore the bulk and thin films of Nb, known to host a significant superconducting gap. The latter is useful for various applications such as the exploration of trivial and topological in-gap states. Here, we focus on the simulations aspects of superconductivity and study the impact of temperature, Cooper-pair coupling and dimensionality on the size of the superconducting order parameter.

Due to the widespread application of (hetero)arylazoles, the development of straightforward functional group-tolerant synthetic methods that enable selective heteroaromatic elaboration under mild conditions aroused considerable attention. Over the last years we were interested in studies aimed to broaden the substrate scope of the direct functionalization of azoles and, in particular, to develop efficient synthetic protocols for the carbon-carbon bond forming reaction by selective palladium-catalyzed Csp2-H bond activation of imidazole derivatives. During these studies, we discovered that the outcome of the Pd-catalyzed arylation of imidazoles with aryl bromides is deeply influenced by the nature of the reaction solvent. Specifically, it is well known that the Pd-catalyzed direct arylation of imidazoles with aromatic halides selectively leads to C-5 monoarylation products when polar aprotic solvents such as DMF (or DMA) are used as a reaction medium, but these solvents are coded as dangerous according to EHS (Environmental, Health, Safety) parameters. Instead, the use of aromatic solvents as the reaction medium for direct arylations, although some of them show good EHS values, is poorly reported, probably due to their low solvent power against reagents and their potential involvement in undesired side reactions. So, with the intention of filling this gap, in this paper, we have developed a selective C-5 arylation procedure in anisole as the solvent, discovering also the unprecedented role of benzoic acid as a promoter of the coupling.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Background: Lithium di-silicate dental ceramics bonding, realized by using different resins, is strictly dependent on micro-mechanical retention and chemical adhesion. The aim of this in vitro study was to investigate the capability of a 1070 nm fiber laser for their surface treatment. Methods: Samples were irradiated by a pulsed fiber laser at 1070 nm with different parameters (Peak Power from 5 kW to 5 kW, RR 20 kHz, speed from 10 to 50 mm/s, total Energy Density from 1.3 to 27 kW/cm²) and the thermal elevation during the experiment was recorded by a Fiber Bragg Grating (FBG) temperature sensor. Subsequently, the surface modifications were analysed by optical microscope, Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Spectroscopy (EDS). Results: With a Peak Power of 5 kW, RR of 20 kHz and speed of 50 mm/s, the microscopic observation of the irradiated surface showed increased roughness with small areas of melting and carbonization. EDS analysis revealed that, with these parameters, there are no evident differences between laser-processed samples and controls. Thermal elevation during laser irradiation ranged between 5 °C and 9 °C. Conclusions: 1070 nm fiber laser can be considered as a good device to increase the adhesion of Lithium di-silicate ceramics.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to interrogate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations and the possible extent of these additional requirements. The relevant data were extracted from the NHANES 2017-2018 datasets, the final cohort of which comprised 2828 non-supplementing adult males and females (aged 18 – 80+ years) with both vitamin C serum concentrations and dietary intake data available. The data was subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: >3.0, 1.36 – 3.0, ≤1.35), weight tertiles (≤72, 72-91, ≥91 kg), BMI tertiles (≤26, 26-32, ≥32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach ‘adequate’ serum concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heaver weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes > 75 mg/day, at intakes < 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population must consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach the same vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. Colitis severity was evaluated using histology and colonoscopy. Mice were mono-inoculated with C. albicans, C. tropicalis or co-challenged with both species. Mice were administered 3% DSS to induce acute colitis. Biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) assay. Abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. Co-challenged mice showed decreased colitis severity compared to mono-inoculated mice. The XTT assay demonstrated a marked decrease of C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface leading to a reduction in biofilm formation.

Background and objectives: Since 2013, highly effective direct-acting (DAA) chronic hepatitis C (CHC) antiviral therapy became available, which has cure rates of over 95%. For choice of optimal CHC treatment, assessment of hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage are necessary. Information about distribution of these parameters among CHC patients in Baltic states and especially in Ukraine is scarce. This study was performed to obtain epidemiological data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (Baltic states) and lower-middle income (Ukraine) countries. Materials and Methods: This was an epidemiological, retrospective, cross-sectional study that included 1451 CHC patients. Demographic and disease information from medical charts was collected for each patient during a single visit. Results: Most frequent suspected mode of viral transmission was blood transfusions (17.8%), followed by injection drug use (15.7%); however, in 50.9% of patients exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%) transmission by the injection drug use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1 - 66.4%; GT3 - 28.1; and GT2 - 4.1%. The prevalence of GT1 was the highest in Latvia (84%), and the lowest in Ukraine (63%, p<0.001). Liver fibrosis stages were distributed as follows: F0 - 12.2%, F1 - 26.3%, F2 - 23.5%, F3 – 17.1% and F4 - 20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p <0.001). Conclusions: This study contributes to the knowledge of epidemiological characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Background: Angelica gigas Nakai, Korean dang-gui, has long been widely used in traditional treatment methods. There have been a number of studies of the health effects of A. gigas and related compounds, but studies addressing effects on blood triglycerides (TG) are lacking. To investigate the effects of A. gigas Nakai extract (AGNE) on TG in Korean subjects, we carried out a 12-week, randomized, double-blind, placebo-controlled clinical trial. Methods: Subjects who met the inclusion criterion (130 mg/dL ≤ fasting blood TG ≤ 200 mg/dL) were recruited for this study. One hundred subjects were assigned to the AGNE group (n=50) or the placebo group (n=50), who were given 1g/day of AGNE (as a gigas Nakai extract 200mg/d) in capsules, and the control group for 12 weeks. Outcomes were efficacy TG, lipid profiles, atherogenic index, and safety parameters were assessed initially for a baseline measurement and after 12 weeks. Results: After 12 weeks of supplementation, TG and very low-density lipoprotein cholesterol (VLDL-C) concentration and TG/HDL-C ratio in the AGNE group were significantly reduced compared to the placebo group (p <0.05). No significant changes in any safety parameter were observed. Conclusions: These results suggest that ingestion of AGNE may improve TG and be useful to manage or prevent hypertriglyceridemia.

Same-day desensitization (SDD) is a procedure in which desensitization to the drug suspected of causing the hypersensitivity reaction (HR) is performed on the same day as the patient's reaction. In rapid drug desensitization (RDD), desensitization to the suspected drug is performed after an allergological study. The aim of the study was to analyze the diagnostic capacity of the allergist in Oncology Day Hospital (ODH) to establish the phenotype of the HR, in the context of SDD, based exclusively on clinical biomarkers. This is a study of patients treated with desensitization on the same day they had a HR. Later an allergological study (clinical history, skin test, risk assessment, serological biomarkers, drug provocation test if applicable) was performed prior to the following administrations. A total of 35 successful SDDs were performed. A high concordance (91.5% of patients) was found between the phenotype suspected by the allergist after the initial assessment of the patient prior to SDD and the final phenotype after subsequent allergological study performed in the Allergy Department. The presence of the allergist at the ODH allows, in addition to initial treatment according to phenotype, desensitization on the day of the reaction. This will lead to personalized and precision allergology.

The interconnection between the objectives of territorial development and the agro-ecological transition highlights the value of past knowledge in the sustainable management of resources and agro-ecological systems. However, retrospection in rural areas presents difficulties due to a lack of data. This paper contributes to the search for such knowledge from the past by developing an interactive methodology capable of combining heterogeneous sources of information and the activation of local collective memory. Its effectiveness is based on ensuring the interoperability of information and communication in an environment simultaneously shaped by geoinformatics and 3D geo-visualizations. This virtual environment fosters participation and interactivity, supported by representations of the paleo-landscape. Furthermore, synergies were achieved between information sources and their integration into local spatial systems. The application example involved identifying a rice field that existed from the 15th to the 19th century in Thessaly, Greece. It is an interesting case because the location and organization of cultivation in combination with its spatio-temporal coordination ensures the sustainable use of natural resources. It appears that the interplay between information and communication facilitates community participation and the activation of its collective memory as a source of information that enriches the search and local intelligence.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds would advance rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize the unstable organocopper compounds. The bidentate ligands can chelate to the same copper atom via ?2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via ?1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via ?2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.

The development of photocurable compositions is in high demand for the manufacture of func-tional materials for electronics, optics, medicine, energy, etc. The properties of the final pho-to-cured material are primarily determined by the initial mixture, which needs to be tuned for each application. In this study we propose to use simple systems based on di(meth)acrylate, polyimide and photoinitiator for the preparation of new photo-curable compositions. It was es-tablished that a fluorinated cardo copolymide (FCPI) based on 2,2-bis-(3,4-dicarboxydiphenyl)hexafluoropropane dianhydride, 9,9-bis-(4-aminophenyl)fluorene and 2,2-bis-(4-aminophenyl)hexafluoropropane (1.00:0.75:0.25 mol) has excellent solubility in di(met)acrylates. This made it possible to prepare solutions of FCPI in such monomers, to study the effect of FCPI on the kinetics of their photopolymerization in situ and the properties of the resulting polymers. According to the obtained data, the solutions of FCPI (23 wt.%) in 1,4-butanediol diacrylate (BDDA) and FCPI (15 wt.%) in tetraethylene glycol diacrylate were tested for the formation of the primary protective coatings of the silica optical fibers. It was found that the new coating of poly(BDDA–FCPI23%) can withstand prolonged annealing at 200°C (72 h), which is comparable or superior to the known most thermally stable photo-curable coatings. The proposed approach can be applied to obtain other functional materials.

The metalloporphyrin heme acts as the oxygen-complexing prosthetic group of hemoglobin in blood. Heme has been noted to survive for many millions of years in fossils. Here we investigate its stability and degra-dation under various conditions expected to occur during fossilization. Oxidative, reductive, aerobic, and anaerobic conditions were studied at neutral and alkaline pH values. Elevated temperatures were applied to accelerate degradation. High-performance liquid chromatography coupled to tandem mass spectrome-try (HPLC-MS/MS) identified four main degradation products. The vinyl residues are oxidized to formyl and further to carboxylate groups. In the presence of air or H2O2, cleavage of the tetrapyrrole ring occurs, and hematinic acid is formed. The highest stability of heme was observed under anaerobic reductive condi-tions (half-life 9.5 days), while the lowest stability was found in the presence of H2O2 (half-life 1 min). We confirmed that the iron cation plays a crucial role in degradation, since protoporphyrin IX, lacking iron, re-mained significantly more stable. Under anaerobic, reductive conditions, the above-mentioned degradation products were not observed, suggesting a different degradation pathway. To our knowledge, this is the first molecular taphonomy study on heme, which will be useful for understanding its fate during fossiliza-tion.

A new di-mannitol adipate ester-based zinc metal alkoxide (DMAE-Zn) was synthesized as a bi-functional PVC thermal stabilizer for the first time. The materials were characterized with Fourier-transform Infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). Characterization results confirmed the formation of Zn-O bonds in DMAE-Zn; and that DMAE-Zn had a high decomposition temperature and a low melting point. The thermal stability of DMAE-Zn on PVC also was tested by conductivity test, thermal aging test, and UV-visible spectroscopy (UV-VIS) test. PVC stabilized by DMAE-Zn had a good initial color and excellent long-term stability. UV-VIS also showed that the conjugated structure in PVC stabilized by DMAE-Zn was almost all of the triene, suggesting that the addition of DMAE-Zn would suppress the formation of conjugated structures above tetraene. Dynamic processing performance of PVC samples tested by torque rheometer indicated that, having a good compatibility with PVC chains in the amorphous regions, DMAE-Zn contributed good plasticizing effect to PVC. DMAE-Zn thus effectively demonstrates bi-functional roles, e.g., thermal stabilizers and plasticizers to PVC. Furthermore, FT-IR, HCl absorption capacity test, and complex ZnCl₂ test were also used to verify the thermal stability mechanism of DMAE-Zn for PVC.

In the paper, by virtue of the Faá di Bruno formula and two identities for the Bell polynomial of the second kind, the authors find a closed form for the Stirling polynomials in terms of the Stirling numbers of the first and second kinds.

Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P &lt; 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (P&lt;0.01) and CRP was increased (P&lt;0.05) in the presence of chorioamnionitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age. In those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants born exclusively for maternal indications.

Motivated from the theory of Hilbert-Schmidt morphisms between Hilbert C*-modules over commutative C*-algebras by Stern and van Suijlekom [J. Funct. Anal., 2021], we introduce the notion of p-absolutely summing morphisms between Hilbert C*-modules over commutative C*-algebras. We show that an adjointable morphism between Hilbert C*-modules over monotone closed commutative C*-algebra is 2-absolutely summing if and only if it is Hilbert-Schmidt. We formulate version of Pietsch factorization problem for p-absolutely summing morphisms and solve partially.

A series of MgAl-layered double hydroxide (MgAl-HT), the calcined form at 500^oC (MgAlO_x) and the re-hydrated one at 25^oC (MgAl-HT-RH) were synthesized. Physicochemical properties of the catalysts were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM). Surface area of the as-synthesized, calcined and re-hydrated catalysts was determined by N₂ physisorption at -196^oC. CO₂-teperature programmed desorption (CO₂-TPD) was applied to determine the basic sites of catalysts. The catalytic test reaction was carried out using benzaldehyde and their derivatives with nitromethane and their derivatives. The Henry products (1-15) were obtained in a very good yield using MgAl-HT-RH catalyst either by conventional method at 90^oC in liquid phase, or under microwave irradiation method. The mesoporous structure and basic nature of re-hydrated solid catalyst were responsible for their superior catalytic efficiency. The robust nature was determined by using the same catalyst for five times, where the product % yield was almost unchanged significantly.

Soil amendments with composted organic materials are recommended to increase soil organic matter (SOM), promote soil fertility, and the Circular Economy. Growing areas of hedged olive groves in southern Iberia peninsula generate huge amounts of olive leaves whose potential as soil organic amendment is not fully studied. An experimental field trial in a hedged olive grove (cv. “Cobrançosa”) was set up near Portalegre, Portugal, to test a compost of olive leaves plus sheep manure (2:1) applied in the row, at soil surface. Three nominal rates (0 or control, 2.5 and 5.0 kg m-2) were used, in a complete randomized block setup (3 treatments, 3 replicas, 9 plots) and soil chemical properties of layers 0-5, 5-15, and 15-30 cm deep were annually monitored. Results (mainly in layer 0-5 cm) showed increases in total N, carbon of the particulate organic matter (POM-C), permanganate oxidizable carbon (POX-C), extractable phosphorus, and zinc, after one year, and increases in soil organic carbon (SOC), C-stock, pHKCl, extractable phosphorus, and zinc, after two years. POX-C was the most sensitive SOM-related indicator, showing increases up to 30 cm deep after one year. This compost improved soil fertility, but should be monitored over longer periods of time, namely for SOC and extractable zinc content.

A recent review of global vitamin C status indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here we provide a narrative of potential factors influencing vitamin C status. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use. Dietary intake can be influenced by cultural aspects such as staple foods and traditional cooking practices. Environmental factors can also affect vitamin C intake and status; these include geographic region, season and climate, as well as pollution. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various non-communicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time, therefore we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global recommended dietary intakes for vitamin C.

Cervical injuries from athletic activities are rare; they can have severe consequences if not diagnosed and managed promptly. The choice of diagnostic imaging modality is pivotal in ensuring timely and accurate diagnosis. We detail the case of a 19-year-old female athlete who sustained a C2 Durel Type II Subclass C fracture during a short-track speed skating championship. Initial evaluation using X-ray imaging at the athletic center medical facility did not detect the injury, allowing her to continue competing. Persistent pain led to further evaluation at our institution, where MRI and CT scans confirmed the fracture. Approximately 45 days post-injury, the patient underwent a successful surgical intervention utilizing O-arm CBCT navigation for C1-C2 dorsal fusion. Post-surgery, she embarked on a comprehensive rehabilitation program and fully recovered within 12 weeks. This case underscores the limitations of relying solely on X-ray imaging for diagnosing cervical fractures post-trauma. Our findings advocate prioritizing CT scans as a primary diagnostic tool in such scenarios, emphasizing the need for a robust diagnostic approach to ensure athlete safety and well.

2,5-Di(hydroxymethyl)furan (DHMF) is a high-value chemical block than can be synthesized from 5-hydroxymethylfurfural (HMF), a platform chemical that results from the dehydration of biomass-derived carbohydrates. In this work, the HMF biotransformation capability of different Fusarium species was evaluated and F. striatum was selected to produce DHMF. The effects of the inoculum size, glucose concentration and pH of the media over DHMF production were evalu-ated by a 23 factorial design. A substrate feeding approach was found suitable to overcome the toxicity effect of HMF towards the cells when added at high concentrations (>75 mM). The pro-cess was successfully scaled-up at bioreactor scale (1.3 L) with excellent DHMF production yields (95%) and selectivities (98%). DHMF was purified from the reaction media with high recovery and purity by organic solvent extraction with ethyl acetate.

In this case series, we examine the impact of the Titan-iR Pro® deep spectrum biotherapeutic device on brain function in healthy individuals. Here we present 15 participants, aged 26-68 years, who enrolled in this open-label study, designed to assess the effect of a single 15-minute course of deep spectrum biotherapy on brain function. Although symptom-free upon enrollment, participants had diverse medical histories with some displaying early signs of cognitive decline. As part of the evaluation, all participants engaged in electroencephalogram (EEG) recording sessions that focused on assessing event-related potential (ERP) evaluations, including audio P300 amplitudes and latencies (speeds), neurocognitive testing, and physical reaction times. Following the Titan-iR Pro intervention an improvement in EEG-based cognitive markers was observed. These results underscore the importance of further investigation into the potential of advanced and deep spectrum photobiomodulation in the prevention and treatment of cognitive decline and other neurological disorders.

Nowadays, digitalization and automation in both industrial and research activities is a driving force for innovations. In recent years, Machine Learning (ML) techniques - the subset of Artificial Intelligence - have been widely applied as a key tool to automize and digitalize numerous in-dustrial processes. ML models can predict specific features, like materials' lifetime in a heating device, based on recently trained algorithms with applied input data. The results of ML algorithms are easy to interpret and can significantly decrease the time of research and decision-making, thus, substituting the trial-error approach. This work presents the state of the art in the application of Machine Learning in the investigation of MgO-C refractories for the steel industry. Also, the work presents an overview of the most commonly used ML algorithms in refractory engineering. So far published results confirm the high performance of ML, e.g., for prediction of oxidation behaviour, optimum graphite content and wear rate of MgO-C refractories, or for clustering materials based on various fused and sintered MgO sources into groups with similar corrosion resistance, thus, permitting to reduce expensive fused raw materials content. Most of the presented works were positively validated via experiment.

Nonalcoholic fatty liver disease (NAFLD) is a liver metabolism-associated steatohepatitis caused by non-alcoholic factors. NAFLD is currently the most prevalent liver disease in the world, affecting one-fourth of the world's population, and its prevalence increases with age. There are no approved drugs specifically for the treatment of NAFLD, and one important reason hindering drug development is the lack of effective biomarkers. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. Coincidentally, hepatocytes are responsible for the major CRP production, and the levels of CRP increase with age. Therefore, CRP is not only a potential marker, but also acts as a key factor driving liver aging and NAFLD. Herein, we reviewed the biological function and production mechanism of CRP and the relationship between CRP and NAFLD. We also comprehensively described the potential molecular mechanisms of CRP-mediated signaling in aging-associated NAFLD. Finally, we proposed possible therapeutic approaches based on the mechanism of CRP signaling in the pathogenesis of NAFLD. We hope this study can provide new insights into the development of aging associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

Consider a uniquely ergodic $C^*$-dynamical system ba\-sed on a unital $*$-endomorphism $\Phi$ of a $C^*$-algebra. We prove the uniform convergence of Cesaro averages $\frac1{n}\sum_{k=0}^{n-1}\lambda^{-n}\Phi(a)$ for all values $\lambda$ in the unit circle which are not eigenvalues corresponding to "measurable non continuous" eigenfunctions. This result generalises the analogous one in commutative ergodic theory presented in [19], which turns out to be a combination of the Wiener-Wintner Theorem (cf. [22]) and the uniformly convergent ergodic theorem of Krylov and Bogolioubov (cf. [15]).

We cultured Parmelina carporrhizans and P. quercina in Corn Meal Agar and 0.2% glucose Malt Yeast Agar for 160 days. Chemosyndrome of natural thalli and mycobiont cultures were analyzed by HPLC. Lecanoric acid, atranorin, chloratranorin and ergosterol were detected in P. carporrhizans thalli, while lecanoric acid, chloratranorin and aliphates were found in P. quercina thalli. The secondary methabolites pattern between thalli and mycobiont culture was completely different in both species. Both species secreted the phenalenone myeloconone C in culture media and was also detected in P. quercina mycobiont aggregates. Interestingly, the phenolic compounds produced by the mycobiont culture of P. carporrhizans are related to those produced by natural thallus by the same biosynthetic pathway, while the chemosyndrome of P. quercina mycobiont implies switch of biosynthetic pathway from acetate-polymalonate pathway to shikimic acid pathway, with pulvinic acid as major compound of mycobiont culture. The role of Myelochonone C, confluentic acid and pulvinic acid produced by mycobiont culture is discussed as possible adaptive vantage in field as photoprotective agent or as byproduct result of stressing artificial culture conditions.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4’-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. 1D-NMR and 2D-NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The excluding of aryl fragment from triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied and considerable fluorosolvatochromism was stated. Moreover, electrochemical investigation and DFT calculations have been performed, their results are consistent with the experimental observation.

Bermudagrass (Cynodon spp.) is one of the drought-resistant warm-season turfgrasses adapted to the southern and transitional zones in the United States. Multiple hybrid varieties have been developed and released for use as a turfgrass and others are in pipeline. Increasing genetic di-versity of commercial varieties is vital to tackle stress tolerance. A DNA profiling study of 21 experimental selections from the Oklahoma State University (OSU) turfgrass breeding program and 11 cultivars was conducted using 51 simple sequence repeat (SSR) primer pairs that spread across the bermudagrass genome. Pairwise genetic relationship analysis among the genotypes using 352 polymorphic bands showed genetic similarity coefficients ranging from 0.59 to 0.89. Cluster analysis using the un-weighted paired group method with arithmetic average (UPGMA) method grouped the entries into six clusters. Correlation analysis identified different levels of pairwise genetic relationship among the entries that largely reflected parental relationship. Di-rectional breeding and selection for cold hardiness or drought resistance created progeny that had distinct genetic diversity in the tested bermudagrasses. It is evident that an increase in genetic diversity of the existing cultivar pool with the release of one or more of the experimental selec-tions for commercial use will strengthen and improve bermudagrass systems.

We recently formulated Modular Dvoretzky, Type-Cotype, Khinchin-Kahane and Grothendieck Inequality problems in the Appendix of \textit{[arXiv:2302.03718v1]}. For the sake of wide accessibility we give a separate treatment of them.

Vitamin C is an essential nutrient that must be obtained through the diet in adequate amounts to prevent hypovitaminosis C and the potentially fatal deficiency disease scurvy. Global vitamin C status and prevalence of deficiency has not previously been reported, despite vitamin C’s pleiotropic roles in both non-communicable and communicable disease. This review highlights the global literature on vitamin C status and the prevalence of hypovitaminosis C and deficiency. Related dietary intake is reported if assessed in the studies. We also explore if global vitamin C status has changed over time. Overall, the review illustrates the shortage of high quality epidemiological studies of vitamin C status in many countries, particularly low- and middle-income countries. The available evidence indicates that vitamin C deficiency is common in low- and middle-income countries and not uncommon in high income settings. Further high quality studies are required to confirm these findings, including in the countries not yet represented, and to fully understand associations with a range of disease processes. Our findings suggest a need for interventions to prevent deficiency in a range of at risk groups and regions of the world.

In this paper, we observe that if X is a set and (Bin(X), □) is the semigroup of binary systems on X, then its center ZBin(X) consists of the locally-zero-semigroups and that these can be modeled as (simple) graphs and conversely. Using this device we show that we may obtain many results of interest concerning groupoids by reinterpreting graph theoretical properties and at the same time results on graphs G may be obtained by considering them as elements of centers of the semigroups of binary systems (Bin(X), □) where X = V(G), the vertex set of G.

With the rise of long-read sequencers and long-range technologies, delivering high-quality plant genome assemblies is no longer reserved to large consortia. Indeed, sequencing techniques but also computer algorithms have reached a point where the reconstruction of assemblies at the chromosome-scale is now feasible at the laboratory scale. Current technologies, and especially long-range technologies, are numerous and selecting the most promising one for the genome of interest is crucial to obtain optimal results. In this study, we resequenced the genome of the yellow sarson, Brassica rapa cv. Z1, using the Oxford Nanopore PromethION sequencer and assembled the sequenced data using current assemblers. To reconstruct complete chromosomes, we used and compared three long-range techniques, optical mapping, Omni-C and Pore-C sequencing libraries commercialized by Bionano Genomics, Dovetail Genomics and Oxford Nanopore Technologies respectively, or a combination of the three, in order to evaluate the capability of each technology.

In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.

This study focused on the characterization of lactic acid bacteria (LAB) in a renowned traditional Italian cheese, Pecorino di Farindola, to select an autochthonous culture and investigate its po-tential for the improvement of safety and functional properties. Two hundred and six LAB isolated throughout production and maturation from nine cheese lots of three farms were identified by 16S rRNA gene sequencing and tested for the presence of genes encoding virulence factors, vancomycin resistance (for enterococci), biogenic amines (BAs) and bacteriocin production, for antimicrobial activity, and for the capacity to survive in the gastro-intestinal tract (GIT) based on tolerance to low pH and bile salts and adhesion to CaCo-2 cells. A Lacticaseibacillus paracasei isolate was used in cheese making and determined a decline of spiked Listeria monocytogenes and Escherichia coli O157 faster than in control cheese. The autochthonous bacterial groups were numerically unaffected, apart from lactobacilli that were recovered in higher numbers in the cheese with added L. paracasei. Based on Repetitive Extragenic Palyndrome (Rep) PCR profiles, the added strain possibly dominated until day 88 in cheese. Results encourage further trials with autochthonous cultures to efficiently inhibit hazardous bacteria and enrich a functional microbiota in Pecorino di Farindola and similar cheeses.

A series of novel N-n-butyl-1,8-naphthalimide derivatives were synthesized via a three-step reaction involving nucleophilic substitution and acylation. All of the compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis, and the crystal structure of N-n-butyl-4-[N’,N’-bis(2`,4`-dichlorobenzoyl)ethylamino]-1,8-naphthalimide was determined. The π-π stacking interactions and hydrogen bonds between the two molecular core planes (naphthalimide ring) and the van der Waals forces between the flexible n-butyl groups resulted in a 3D long-chain structure. The UV-vis and fluorescence properties of the title compounds were investigated. The results indicated that the monosubstituted 1,8-naphthalimide derivatives bearing an electron-donating group on the benzene ring or a structure with a larger conjugative effect exhibited enhanced fluorescence properties.

Nanotechnology sparks discussions and concerns about the impacts of new nanomaterials on health and the environment. It holds importance in various domains due to its unique struc-tures. Carbon dots (C-dots) are versatile nanomaterials with applications in bioimaging, sensing, catalysis, polymers, solar cells, and more. They offer desirable characteristics such as stability, cost-effectiveness, biocompatibility, and high photoluminescent quantum yield. C-dots have the potential to replace expensive fluorophores in solar cells. They are catego-rized as carbon quantum dots, graphene quantum dots, and carbonized polymer dots. C-dots have outstanding optical and photoelectric properties with low toxicity. Bottom-up and top-down approaches are used for the synthesis of carbon dots (CDs), with each method im-pacting their physicochemical characteristics. The choice of synthesis method depends on de-sired properties and application requirements. Researchers combine these methods and ex-plore new approaches to enhance synthesis efficiency and tailor CD properties. CDs have di-verse chemical structures with modified oxygen, polymer-based, or amino groups on their surface. Various characterization methods such as HRTEM, XPS, and optical analysis (PL, UV) are used to determine CD structure. Carbon dots (CDs) are cutting-edge fluorescent nano-materials with remarkable qualities such as biocompatibility, low toxicity, environmental friendliness, high water solubility, and photo-stability. They are easily adjustable in terms of their optical properties, making them highly versatile in various fields. CDs find applications in bio-imaging, nanomedicine, drug delivery, solar cells, LEDs, photo-catalysis, elec-tro-catalysis, and other related areas.

The purpose of the study is to show the effect of the intake of vitamin C obtained from a diet rich in fruit and vegetables or vitamin C supplements on the level of vitamin C in the plasma. The level of vitamin C in plasma were determined before the study (T1), and after five months (T2). Moreover, a medical record was carried out and a questionnaire on the habits such as general eating and specific consumption of food rich in vitamin C. Both of them were completed before and after five months. In addition, related anthropometric analyses were carried out. The results of the first determination of vitamin C level in plasma were between 1.0 and 16.0 mg/L and the results of the second determination of vitamin C in plasma were between 4.9 and 14.1 mg/L. Furthermore, it was identified that 50% of the questioned people had a low fruit intake. Raw vegetables were consumed by fewer people, the intake being higher during the main meals. The correlation of plasma vitamin C with the eating habits of the subjects to the study points out an interdependence between the consumption of fruit and vegetables and the level of vitamin C in the plasma.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.

Aging is a complex process associated with tissue degeneration and an increased risk of age-related diseases. This study aimed to evaluate the impact of Terasen®, a nutraceutical containing standardized extracts of Euterpe oleracea, Myrciaria dubia, and purified oil of Bixa orellana and Astrocaryum aculeatum on the lifespan of Caenorhabditis elegans, a widely used model organism for aging research. The findings demonstrated that Terasen® exhibited significant antioxidant activity and influenced the feeding behavior of C. elegans, leading to a reduced pharyngeal pumping rate and a decreased number of offspring produced by treated individuals. Notably, Terasen® also displayed a remarkable ability to extend the lifespan of C. elegans. These findings suggest that Terasen® may possess promising anti-aging effects in vivo, warranting further investigation.

The involvement of NK and other cytotoxic cells is considered the first defense' line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells, the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers, some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. Despite having demonstrated multiple correlations, it should be noted that immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.

Modified nucleobases are potentially useful building blocks when containing catalytically active functionalities and could be introduced in chiral tridimensional molecules such as nucleic acids, which creates the premises for the development of novel catalytic species. Herein we describe the synthesis of a novel β-C-nucleoside bearing a diol group at anomeric position, amenable as metal ligand or as organo-catalyst. The abasic ligand was successfully prepared and inserted into complementary DNA strand.

Hepatitis C virus (HCV) core protein is a multifunctional protein that is involved in proliferation, inflammation and apoptosis mechanism of hepatocytes. HCV core protein genetic variability has been implicated in various outcomes of HCV pathology and treatment. In the present study, we aimed to analyze the role of HCV core protein in tumor necrosis factor α (TNFα)-induced death under the viewpoint of HCV genetic variability. Immortalized hepatocytes (IHH), and not the Huh7.5 hepatoma cell line, stably expressing HCV subtype 4a and HCV subtype 4f core proteins showed that only HCV 4a core protein could increase sensitivity to TNFα-induced death. Development of two transgenic mice expressing the two different core proteins under the liver-specific promoter of transthyretin (TTR) allowed for the in vivo assessment of the role of core in TNFα-induced death. Using the TNFα-dependent model of lipopolysaccharide/D-galactosamine (LPS/Dgal) we were able to recapitulate the in vitro results in IHH cells in vivo. Transgenic mice expressing HCV 4a core protein were more susceptible to the LPS/Dgal model while mice expressing HCV 4f core protein had the same susceptibility as their littermate controls. Transcriptome analysis in liver biopsies from these transgenic mice gave insights into HCV core molecular pathogenesis, while linking HCV core protein genetic variability to differential pathology in vivo.

Abstract: Carbohydrates form the major source of energy in Asian diets. A lower carbohydrate diet became the recommended golden standard for healthy lifestyle. However, the effects of low-carbohydrates diet on health in apparently healthy individuals have been poorly studied, especially in relation to insulin resistance syndrome (IRS). A total of 120 healthy weight participants with no previous history of a major medical condition and an average BMI of ≤ 25kg/m2 were recruited. Self-reported dietary intake and objective physical activity by accelerometry were tracked for seven days. Participants were divided into three categories according to their dietary intake of carbohydrates. Blood samples were collected for metabolic markers analysis. HOMA of insulin resistance (HOMA-IR), β-cell function (HOMA-B) and C-peptide were used to evaluate glucose homeostasis. The consumption of low carbohydrates (less than 45% of total energy) significantly correlated with higher HOMA-IR, Lower HOMA-β % compared to moderate carbohydrate intake (between 45% to 65%). However, only the HOMA-β % was significantly influenced by carbohydrates intake. Moreover, low carbohydrates intake was significantly associated with elevated C-peptide secretion. The substitution of carbohydrates with other macronutrients, such as fat and proteins in the Atkins/ketogenic diet, resulted in a pronounced induction of IRS-related inflammatory markers; FGF2, IP-10, IL-6, IL-17A, MDC and reduction of IL-13. Overall, the presented data highlight, for the first time, that low carbohydrate intake results in significant glucose homeostasis imbalance that may be driven by a heightened state of inflammatory response.

Vitamin C is important in preventing and slowing the progression of many diseases. There is significant evidence linking periodontal disease and vitamin C. We aimed to systematically review studies addressing the relationship between vitamin C and periodontal disease and the preventive ability of vitamin C against periodontal disease. Electric searches were performed using PubMed, EMBASE, Cochrane Library, and Web of Science. Studies addressing the relationships between periodontal disease and vitamin C in adults aged over 18 years were included. Quality assessment was done using Critical Appraisal Skills Program guideline and GRADE-CERQual. Seventy hundred and sixteen articles were retrieved and fifteen articles (7 cross-sectional studies, 2 case-control studies, 2 cohort studies, and 4 randomized controlled trial [RCT]) were selected by reviewing all articles. Vitamin C intake and blood level were negatively related to periodontal disease in all 7 cross-sectional studies. Subjects who suffer from periodontitis presented lower vitamin C intake and lower blood vitamin C level than subjects without periodontal disease in the two case-control studies. Patients with lower dietary intake or lower blood level of vitamin C showed greater progression of periodontal disease than did the controls. Intervention using vitamin C administration improved gingival bleeding in gingivitis but not in periodontitis. Alveolar bone absorption was also not improved. The present systematic review suggested that vitamin C contributes to reduced risk of periodontal disease.

Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on dsRNAs. Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here, we performed high-throughput RNA sequencing of wild-type and ADAR mutant C. elegans worms after heat-shock to analyze the effect of heat-shock stress on the expression pattern of genes. We found that ADAR regulation following heat-shock does not directly involve heat-shock related genes. Our analysis also revealed that lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes following heat-shock in ADAR mutant worms. The same group of genes is downregulated in ADAR mutant worms under permissive conditions, which is likely, considering that A-to-I editing protects endogenous dsRNA from RNA-interference (RNAi). Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shed new light on the dynamics of gene expression under heat-shock in relation to ADAR function.

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

In the face of climate change, bringing more useful alleles and genes from wild relatives of wheat is crucial to develop climate-resilience varieties. We used two populations of backcrossed recombinant inbred lines (BIL1 and BIL2), developed using two intra-specifically diverse Aegilops tauschii accessions from lineage 1 and lineage 2, respectively, and backcrossing to common wheat cultivar ‘Norin 61’. The study aimed to identify quantitative trait loci (QTL) associated with heat stress (HS) tolerance. The two BILs were evaluated under heat stress environments in Sudan for phenology, plant height (PH), grain yield (GY), biomass (BIO), harvest index (HI), and thousand kernel weight (TKW). Grain yield was significantly correlated with BIO and TKW under HS; therefore, stress tolerance index (STI) was calculated for these traits as well as for GY. A total of 16 heat tolerant lines were identified based on GY and STI-GY. The QTL analysis performed using inclusive composite interval mapping identified a total of 40 QTLs in BIL1 and 153 QTLs in BIL2 across all environments. We detected 39 QTLs associated with GY-STI, BIO-STI, and TKW-STI in both populations (14 in BIL1 and 25 in BIL2). The QTL associated with STI were detected on chromosomes 1A, 3A, 5A, 2B, 4B, and all the D-subgenomes. We found that QTL detected only under HS for GY on chromosome 5A, TKW on 3B and 5B, PH on 3B and 4B, and grain filling duration on 2B. The higher number of QTLs identified in BIL2 for heat stress tolerance suggests the importance of assessing the effects of intraspecific variation of Ae. tauschii in wheat breeding as it could modulate the heat stress responses/adaptation. Our study provides useful genetic resources for uncovering heat-tolerant QTLs for wheat improvement for heat stress environments.

In globe artichoke both the edible portion and the waste biomass are recognized as valuable sources of bioactive compounds. For this study, heads with 30 cm-long floral stems, including 2-3 leaves, were harvested from five genotypes which included two traditional vegetatively-propagated varietal types (‘Brindisino,’ and ‘Violetto di Foggia,’) and three "seed"-propagated hybrids (‘Tempo,’ ‘Opal,’ and ‘Madrigal’). The study aimed to determine the total and individual polyphenolic concentrations (measured spectrophotometrically and by HPLC) and antioxidant activity (AA) in different artichoke parts, namely the "hearts" (H), head waste (HW), stem waste (SW), and leaf waste (LW). ‘Brindisino’ SW exhibited the highest accumulation of luteolin (26,317 mg kg−1 F.W.), while ‘Tempo’ H displayed the highest cynarin content (190 mg kg−1 F.W.). ‘Tempo’ HW and H showed the highest levels of apigenin (640 mg kg−1 F.W.), and the greatest source of chlorogenic acid was found in the HW of ‘Opal’ and the H of ‘Brindisino’ (4,300 mg kg−1 F.W.). The hybrids generally exhibited lower total polyphenolic concentrations than the traditional genotypes, particularly evident in the LW. The SW demonstrated the highest concentration of total polyphenols (18,000 mg kg−1 F.W.), followed by the edible H and non-edible HW (12,000 mg kg−1 F.W.), while the LW exhibited the lowest concentration (2,000 mg kg−1 F.W.). Interestingly, the AA did not precisely align with the total polyphenolic concentration, showing slight variations between the examined parts and genotypes.

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

Aim. The purpose of the work was the development of a machine learning model for diagnosing the stage of liver fibrosis in patients with chronic viral hepatitis C according to the data of routine clinical examination. Materials and methods. A total of 1240 patients with chronic viral hepatitis C was examined. A set of data obtained from 689 patients balancing by the stage of liver fibrosis was used for developing and testing machine learning models. 9 routine clinical parameters were selected as the most important predictors for determining the likelihood of liver fibrosis the 3–4 stages presence: age, height, weight and body mass index of the patient, the number of platelets in the clinical blood test, levels of alanine transaminase, aspartate transaminase, gamma-glutamyltransferase, and total bilirubin in a biochemical blood test. Results. The accuracy of the developed method for determining the 3–4 stages of liver fibrosis in patients with chronic viral hepatitis C in comparison with the «gold standard» of diagnosis (liver biopsy) was 80.56% (95% CI: 69.53–88.94%), sensitivity — 66.67%, specificity — 94.44%. Conclusion. The developed method is an alternative to more expensive and geographically inaccessible studies. The method does not require the purchase of additional equipment or software, as well as additional laboratory tests, when used in real clinical practice. The introduction of the method into clinical practice can help to solve the problem of low material and territorial availability of diagnostic tests and allow determining the stage of liver fibrosis in patients with chronic viral hepatitis C.

The following article analyzes Italian companies with more than 10 employees that use online sales tools. The data used were acquired from the ISTAT-BES database. The article first presents a static analysis of the data aimed at framing the phenomenon in the context of Italian regional disparities. Subsequently, a clustering with k-Means algorithm is proposed by comparing the Silhouette coefficient and the Elbow method. The investigation of the innovative and technological determinants of the observed variable is carried out through the application of a panel econometric model. Finally, different machine learning algorithms for prediction are compared. The results are critically discussed with economic policy suggestions.

In the following article I analyze the determinants of regular internet users in the Italian regions. The data is analyzed both in terms of static analysis and also through the application of the k-Means algorithm optimized with the Elbow method. Subsequently, an econometric model is presented for estimating regular internet users in the Italian regions based on variables that reflect the state of technological innovation and digital culture. The results are analyzed and discussed in light of the implications that digitalisation has for triggering economic growth.

in the following article I analyze the trend of cultural and creative employment in the Italian regions between 2004 and 2022 through the use of ISTAT-BES data. After presenting a static analysis, I also present the results of the clustering analysis aimed at identifying groupings between Italian regions. Subsequently, an econometric model is proposed for estimating the value of cultural and creative employment in the Italian regions. Finally, I compare various machine learning models for predicting the value of cultural and creative employment. The results are critically discussed through an economic policy analysis.

In the following article I take into consideration the role of knowledge workers in the Italian regions. The analysed data refers to the ISTAT-BES database. The metric analysis consists of an in-depth analysis of the trends of the regions and macro-regions, followed by clustering with the k-Means algorithm, the application of machine learning algorithms for prediction, and the presentation of an econometric model with panel methods date. The results are also critically discussed in light of the North-South divide and the economic policy implications.

Artificial intelligence and Quantum science supports path-breaking technologies for main technological change. The investigation goal of this study is to examine their scientific and technological development to explain drivers of these disruptive technologies. Analyses of data, based on publications and patents in quantum science and artificial intelligence, with a technometric model show that that quantum science and technology has a growth rate of 1.07, artificial Intelligence ha a rate of growth of 1.37, whereas the interaction of quantum science and artificial intelligence generates a convergent technological trajectory that has an accelerated rate of growth of 1.58, higher than trends of these technologies taken individually. These findings here clarify one of the fundamental determinants of the evolution of path-breaking technologies that can support decision making of policymakers, technology analysts and R&amp;D managers to direct R&amp;D investments towards fruitful inter-relationships between radical technologies that foster scientific and technological change in knowledge economies.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, like empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate–induced VC in mouse VSMCs to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate–induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE−/− mice on a high-phosphate diet.

This study develops a vitamin C controlled-release system trackable via color changes as a function of vitamin C release. The system is composed of coaxial microfibers prepared via coaxial electrospinning, with a core of poly(ethylene oxide) (PEO) incorporating vitamin C, and a shell composed of polycaprolactone (PCL) containing polydiacetylene (PDA) as the color-changing material. The shell thickness was controlled by adjusting the amount of PCL ejected during electrospinning, allowing the regulation of the release rate of vitamin C. When vitamin C added to PEO penetrated the PCL layer, the color of PDA changed from blue to red, indicating a color change. The results of this study can be applied to devices that require immediate detection of vitamin C release levels.

In this study, we used Chlorella vulgaris (C.vulgaris) grown in the dairy wastewater as biomass to produce a third-generation biodiesel. The lipids were extracted from the biomass and the biodiesel obtained by transesterification. Following ASTM and EN guidelines, the biodiesel was assessed along with its density, viscosity, heating value, and flash point. Gas chromatography was used to evaluate the concentration, composition, and type of fatty acid methyl esters. The results showed a biodiesel yield of 93% with a composition of 33% saturated, 28% monounsaturated, and 37% polyunsaturated. Engine testing was carried out to monitor the levels of CO, CO2, NOx, and smoke emissions as well as to assess the biodiesel performance. Results demonstrate the possibility of producing third-generation biodiesel from C. Vulgaris cultivated in dairy wastewater. The proposed process valorize the dairy wastewater and might represent an alter-native approach for biodiesel production and the disposal of the wastewater.

Various implementations of the Move with Interleaving transform are discussed in this paper, with the transformation itself explained briefly at first. The transform has an expected time complexity of O(n), where n represents the length of the sequence being transformed. The importance of implementation also grows as the sequences become longer. The paper explains three different implementations: the first uses the standard vector, the second employs a lookup table, and the third utilises a dynamic linked list with a pool of released records. The experiments were conducted on 32 greyscale raster images of various contexts and sizes. All three solutions were implemented in both C++ and Java, and then executed on three different platforms: a personal computer running MS Windows and Linux, and a Raspberry Pi 2 with Linux. The implementation based on the dynamic linked list was the fastest, and outperformed the vector-based implementation by more than 1800%. While direct comparisons between results on the Raspberry Pi and those on the modern personal computer may not be straightforward, a consistent pattern prevails: the dynamic linked list implementation outperformed the other two consistently, and the C++ code was faster than the code written in Java. The difference was most evident on the Raspberry Pi.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose of 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrates that ACN inhibited c-Myc expression through CNOT2 and MID1IP1 and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

Using a safe subset of C++ is a promising direction for increasing the safety of the programming language while maintaining its performance and productivity. In this paper, we examine how close existing C/C++ code is to conforming to a safe subset of C++. We examine the rules presented in existing safe C++ standards and safe C++ subsets. We analyze the code characteristics of 5.8 million code samples from the Exebench benchmark suite and 5 modern C++ applications using a static analysis tool. We find that raw pointers, unsafe casts, and unsafe library functions are used in both C++ code at large and modern C++ applications. In general, C++ code at large does not differ much from modern C++ code, and continued work will be required to transition from existing C/C++ code to a safe subset of C++.

Osteoclasts (OCs) are the multinucleated, bone-resorbing giant cells originally differentiated from a monocyte/macrophage lineage. OC differentiation and maturation, also called osteoclastogenesis, are strictly regulated by a variety of signaling pathways primarily induced by the interactions of two prerequisite cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-κB ligand (RANKL) to their respective surface receptors, c-fms and RANK, in OC precursors (pre-OCs). Rab11 has emerged as the spatiotemporal regulators of intracellular vesicular transport in the endosomal recycling system; however, how it regulates osteoclastogenesis is incompletely understood. OC-triggered bone resorption is best characterized to be immensely dependent upon lysosomal function, the intracellular acidic organelles containing more than 50 acid hydrolases secreted into bone matrix microenvironment (BME). On the contrary, it is little known about the lysosomal function on modulating the turnover of c-fms and RANK surface receptors via Rab GTPase-mediated vesicular transport, thereby dictating osteoclastogenesis. In this review, I briefly describe the mechanism underlying lysosome-induced osteoclastogenesis via the Rab11-mediated modulation of the surface receptors in OCs.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Liposome-mediated delivery is a possible means to overcome several shortcomings with C. elegans as a model for identifying and testing drugs that retard aging. These include interactions between drugs and the nematodes’ bacterial food source, and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in C. elegans. Liposome encapsulation led to enhanced effects on lifespan, using smaller quantities of compound, and enhanced uptake of three dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, indicating that liposomes cannot ensure uptake of any compound. Of six compounds previously reported to extend lifespan (vitamin C, N-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT) and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially-mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection, and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for C. elegans. They also show how nematode-bacteria interactions can determine the effects of compounds on C. elegans lifespan in a variety of ways.

COVID-19 infection in the pediatric population usually leads to a mild illness, however, a rare but serious complication of MIS-C has been seen in children. MIS-C usually presents 2-4 weeks after COVID-19 infection or exposure, and rare reports have been documented in neonates. Vaccinations for COVID-19 have been approved for children 6 months and above in the United States, and recent reports suggest significantly low prevalence and risk of complications of MIS-C in vaccinated children compared to unvaccinated children. Vaccinations for COVID-19 are safe and recommended during pregnancy and prevent severe maternal morbidity and adverse birth outcomes. Evidence from other vaccine-preventable diseases suggests that through passive transplacental antibody transfer, maternal vaccinations are protective against infections in infants during the first 6 months of life. Various studies have demonstrated that maternal COVID-19 vaccination is associated with the presence of anti-spike protein antibodies in infants, persisting even at 6 months of age. Further, completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy is associated with reduced risk for COVID-19–associated hospitalization among infants aged 6 months or less. Therefore, it can be hypothesized that maternal COVID-19 vaccination can reduce the risk of and severity of MIS-C in infants. In this article, we review the literature to support this hypothesis.

Food-grade titanium dioxide (E171) contains variable percentages of TiO2 nanoparticles (NPs) posing awareness about its potential effects on human and animal health. Despite many studies, the actual relationship between the physicochemical properties of E171 NPs and their interaction with biological targets is still far from clear. We evaluated the acute toxicity of E171 in invertebrate and vertebrate animals. In the nematode C. elegans, E171 up to 1.0 mg/mL did not affect worm’s viability and lifespan but significantly impaired pharyngeal function, reproduction, and development. We also focused our attention on the fate of E171 after its penetration inside the circulatory tree, investigating whether its intravenous administration to mice could result in an acute over-absorption to filter organs. A significant increase of hepatic Ti concentration and the formation of microgranulomas were observed. Interstitial inflammation and parenchymal modification were found in lung coupled with Ti accumulation, probably due to the propensity of TiO2 NPs to agglomerate, as demonstrated by transmission electron microscopy experiments showing that the incubation of E171 with serum promoted the formation of compact clusters. Overall, these data emphasize, once again, the actual risk for human and animal exposure to E171.

This study aimed to investigate the efficacy of DìRelaxTM, a nutraceutical formulated to reduce anxiety in dogs. The CBARQ questionnaire, some clinical investigations, and the impossible task test were performed in dogs before and after the treatment. Results showed an ameliorative effect on the performances of treated dogs during the solvable phases, with a significant decrease of the time needed to solve the task. No behavioral difference was found between treated and untreated anxious dogs during the unsolvable phase. According to the results from the C-BARQ questionnaire, some of the behaviors appear improved. In general, this study suggests that DiRelaxTM can be safely administered with no adverse effects and can exercise a beneficial effect on anxious dogs by enhancing their cognitive abilities.