Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Introduction: Polycystic Ovary Syndrome (PCOS) is an endocrinologic disorder that affects 5-15 % of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, a characteristic multi-follicular morphology of the ovary, an elevated ratio of LH/FSH, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. Inflammatory processes consist of the acute inflammatory response and resolution processes initiated concomitantly. "Classical" pro-inflammatory lipid mediators like prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. SPM biosynthesis starts from the essential polyunsaturated fatty acids DHA, DPA, or EPA via certain hydroxylated intermediates (18-HEPE, 17-HDHA, 14-HDHA). The present study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Blood samples were taken (20 ml), separated into plasma and serum, and analyzed by HPLC/MS-QQQ. Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as comparator group, were recruited for the study. The main outcome measures were: Pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA; SPMs (Resolvins, Maresins, Protectins, Lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). Ratio [(sum of pro-inflammatory molecules)/sum of SPMs]. Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio [(sum of pro-inflammatory molecules) / (sum of SPMs plus hydroxylated intermediates)] reflecting the inflammatory state was significantly lower in the group of healthy women. Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

The effective integration of aerial remote sensing data and ground multi-source data has always been one of the difficulties of quantitative remote sensing. A new monitoring mode is designed which installs the hyperspectral imager on the UAV and places a buoy spectrometer on the river. Water samples are collected simultaneously to obtain in situ assay data of total phosphorus, total nitrogen, COD, turbidity and chlorophyll during data collection. The cross correlogram spectral matching (CCSM) algorithm is used to match the data of the buoy spectrometer with the UAV spectral data to reduce the UAV data noise significantly. An absorption characteristics recognition algorithm (ACR) is designed to realize a new method for comparing UAV data with laboratory data. This method takes into account the spectral characteristics and the correlation characteristics of test data synchronously. It is concluded that the most accurate water quality parameters can be calculated by using the regression method under five scales after the regression tests of multiple linear regression method (MLR), support vector machine method (SVM) and neural network (NN) method. This new working mode of integrating spectral imager data with point spectrometer data will become a trend in water quality monitoring.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.

Background: Metabolic flux analysis (MFA) is an indispensable tool in metabolic engineering. The simplest variant of MFA relies on an overdetermined stoichiometric model of the cell’s metabolism under the pseudo-steady state assumption, to evaluate the intracellular flux distribution. Despite its long history, the issue of model error in the overdetermined MFA, particularly misspecifications of the stoichiometric matrix, has not received much attention. Method: We evaluated the performance of statistical tests from linear least square regressions, namely Ramsey RESET test, F-test and Lagrange multiplier test, in detecting model misspecifications in the overdetermined MFA, particularly missing reactions. We further proposed an iterative procedure using the F-test to correct such an issue. Result: Using Chinese hamster ovary and random metabolic networks, we demonstrated that: (1) a statistically significant regression does not guarantee high accuracy of the flux estimates, (2) the removal of a reaction with a low flux magnitude can cause disproportionately large biases in the flux estimates, (3) the F-test could efficiently detect missing reactions, and (4) the proposed iterative procedure could robustly resolve the omission of reactions. Conclusion: Our work demonstrated that statistical analysis and tests could be used to systematically assess, detect and resolve model misspecifications in the overdetermined MFA.

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion of interleukin (IL)-1β. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotics carbenicillin on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of gram-positive and gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Aflatoxin M1 (AFM1), a carcinogenic toxin, mainly contaminates cow milk and poses significant challenges to the dairy industry and, thereby, public health in most tropical countries, including Ethiopia. This study aimed to investigate the prevalence and level of AFM1 in raw cow milk collected from Specialized Dairy Farms and Milk Vendors in three Urban Centers: Chiro town, Dire Dawa, and Harar cities in Eastern Ethiopia. 180 milk samples were collected from two major Milk Sources: Specialized Dairy Farms (N=90) and Milk Vendors (N=90) using a simple random sampling technique. AFM1 was analyzed using high-performance liquid chromatography. The study revealed that, 63.9% (115/810) prevalence and 0.179±0.48µg/L mean of AFM1 level in milk, which 39.13% and 26.08% exceed the tolerable limits of EU and FDA respectively. A 40.0% prevalence and 0.344±0.72µg/L average of AFM1 in the milk from Dire Dawa city was significantly higher than the samples from other Urban Centers. However, 30.43% and 29.57% prevalence as well as 0.055±±0.13µg/L and 0.140±0.33µg/L average of AFM1 in milk from Chiro town and Harar city, respectively were not significant. Furthermore, milk samples from Dairy Farms revealed a higher prevalence (57.39%) and level (0.252±0.64µg/L) of AFM1 than Milk Vendors, with a prevalence of 42.61% and an average of 0.107±0.21µg/L. Therefore, this study concludes that substantial milk samples were contaminated by AFM1 and urges the need to enhance farmers' awareness on mitigation.

Species identification and phylogenetic relationships clarification are fundamental goals in species delimitation. Yet these tasks pose challenges when based on morphologies, geographic distribution, and genomic data. Previously, two new species of fern genus Bolbitis, B. × multipinna and B. longiaurita, were described based on morphological traits, are phylogenetically intertwined with B. sinensis and fail to form monophyletic groups. To address the unclear phylogenetic relationships within the B. sinensis species complex, RAD sequencing was performed on 65 individuals from five populations. Our integrated analysis of phylogenetic tree, neighbor net, and genetic structure, indicate that the B. sinensis species complex should not be considered as separate species. Moreover, our findings reveal differences in the degree of genetic differentiation among five populations, ranged from low to moderate, which might be influenced by geographical distance and gene flow. The Fst values also confirmed that genetic differentiation intensifies with increasing geographic distance. Collectively, this study clarifies the complex phylogenetic relationships within the B. sinensis species complex, elucidates the genetic diversity and differentiation across the studied populations, and offers valuable genetic insights that contribute to the broader study of evolutionary relationships and population genetics within the Bolbitis species.

Diabetic retinopathy (DR) is the primary factor leading to vision impairment and blindness in diabetic people. Uncontrolled diabetes can damage the retinal blood vessels. Initial detection and prompt medical intervention are vital in preventing progressive vision impairment. Today's growing medical field poses more significant workload and diagnostic demands on medical professionals. In the proposed study, a convolutional neural network (CNN) is employed to detect the stages of DR. This research is crucial for studying DR because of its innovative methodology incorporating two different public datasets. This strategy enhances the model's capacity to generalize unseen DR images, as each dataset encompasses unique demographics and clinical circumstances. The network can learn and capture complicated hierarchical image features with asymmetric weights. Each image undergoes preprocessing using contrast-limited adaptive histogram equalization (CLAHE) and the discrete wavelet transform (DWT). The model is trained and validated using the combined datasets of Dataset for Diabetic Retinopathy (DDR) and the Asia Pacific Tele-Ophthalmology Society (APTOS). The CNN model is tuned with different learning rates and optimizers. The CNN model with Adam optimizer achieved 70% accuracy and an area under curve (AUC) score of 0.82. The recommended study results may reduce diabetes-related vision impairment by early DR severity identification.

High quantities of biomass produced in greenhouses create environmental problems, as this side stream and its downgraded products are not further used in the production cycle. The aim of our research was the identification and semi-quantification of molecules extracted from vegetative tomato plant residues with sustainable green alternative solvents using vacuum-assisted soxhlet and solid-liquid extraction to evaluate the possibilities for high-value applications. To identify compounds, GC-MS analysis, and the Folin-Cioalteau method was used. In sum, 285 different compounds have been assigned to 383 detected peaks using GC-MS analysis. The solvents 2-MTHF and ethyl acetate, compared to ethanol and hexane, provided better results with a maximum number of 99 ± 8.83 compounds, a maximum total concentration of 5,894.82 ± 586.48 and 3,363.02 ± 71.14 mg NEQ kgdw-1 and a total phenolic content of 2,143.25 ± 155.17 and 1,605.92 ± 66.46 mg GAE kgdw-1, respectively. With 781.2 ± 112.66 and 718.25 ± 54.89 mg NEQ kgdw-1 the compound neophytadiene was the most common terpene in ethyl acetate and 2-MTHF extracts, respectively. It can be concluded that vegetative tomato plant residues contain a high variety of bioactive molecules. Green solvents, such as 2-MTHF and ethyl acetate, enhance the extraction of these molecules from the solid matrix.

Smart manufacturing encompasses a category of manufacturing that employs computer-integrated capabilities and technologies to enhance supply chain optimization, production efficiency, and recyclability. Yet limited studies have been conducted to optimize these prospects from the perspective of low resource countries where such innovative studies have not been adequately explored. This paper aims to examine the implications of smart manufacturing practices (Smart Procurement, Smart Supply Chain, Smart Production Planning and Control, Automation and Industrial Robot, and Supply Chain Configuration) on pro-environmental behaviour and develop a baseline moderated mediation model to explain the relationship between smart manufacturing and pro-environmental behaviour with a role of green dynamic capability, and environmental orientation. This study is anchored on quantitative research approach, deductive reasoning, and explanatory design. Cross – sectional survey data have been obtained from 382 manufacturing companies in Ghana. Our hypotheses have been tested using Structural Equation Modelling and SMART-PLS version 3.8.9. The study has revealed that smart manufacturing practices significantly and positively relate to pro-environmental behaviour. Moreover, green dynamic capability and environmental orientation moderate the relationship between smart manufacturing and pro-environmental behaviour. The implications of the study include the emergence of a baseline model to guide policymakers, practitioners, and academicians to explain the relationship between smart manufacturing and sustainable manufacturing in the context of developing countries. Again, the social implication of the study includes the realisation of decent job and economic growth, responsible consumption and production as well as actions taken to combat climate change.

The study delves into the multifaceted landscape of human-macaque conflict within temple ecosystems, with a specific focus on Bonnet Macaques. In the context of intertwined religious, cultural, and social values, understanding public attitudes towards these commensal species becomes pivotal. The research aims to decipher the socio-economic factors that shape perceptions of human-monkey conflict within temples and to explore public attitudes within sacred groves. To achieve these objectives, a comprehensive questionnaire was administered through household interviews to 100 residents living within both a 1 sq. km and a 2 sq. km radius of the study area, ensuring direct participant interaction. The survey, taking approximately 40 minutes per participant, examined six variables, including occupation, religion, and annual income. The data collected was analysed using SPSS ver. 24 software, employing the chi-square test of independence to explore associations between categorical variables. The findings revealed that occupation and religion emerged as influential factors in shaping perceptions of Bonnet Macaques as problematic. While annual income hinted at significance, age, education, and knowledge of Kysannur Forest Disease (KFD) did not significantly impact Bonnet Macaque perception. Interestingly, age emerged as a significant factor influencing the perception of the monkeys' religious significance, whereas only education and religious affiliation impacted feeding practices towards the monkeys. Surprisingly, other demographic variables such as age, gender, occupation, and income showed no significant influence on monkey feeding practices. These results underscore the intricate interplay of socioeconomic, cultural, and religious factors in shaping public attitudes and behaviours towards Bonnet Macaques. The study further sheds light on the impact of education and religious affiliation on feeding practices, emphasizing the need for nuanced conservation strategies. Recognizing these complexities is crucial for developing culturally sensitive conservation efforts. By acknowledging the influential factors identified in this research, conservation strategies can be tailored to specific communities, fostering harmonious coexistence between humans and Bonnet Macaques in temple ecosystems. This nuanced approach ensures that conservation efforts are not only effective but also respectful of the diverse socio-cultural contexts within which they are implemented.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic crosslinking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers, such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL) or cell-free supernatants of planktonic or flow cell biofilm effluent of wild P. aeruginosa (PAO1), the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and -80 °C and were ready for on-the-spot sensing without the need for recovery. This whole-cell biosensor demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.

Extraction techniques of important bioactive molecules from the major concern of Seafood byproducts are getting emphasis for better valorization. Employing green extraction technologies for efficient and quality production of these bioactive molecules is also strictly required. Hence, understanding the extraction process parameters to effectively design an applicable optimization strategy could make this real. In this review, statistical optimization strategies applied for the extraction process parameters of bioactive molecules from Seafood byproducts are focused. The type of experimental designs, and techniques applied to criticize and validate the effects of independent variables on the extraction output was addressed. Dominant parameters studied were enzyme/substrate ratio, pH, time, temperature and power of extraction instruments. The yield of bioactive compounds, chitin and chitosan, proteins and peptides, enzymes and carotenoids (Astaxanthins) were the most studied responses. Efficiency and/or economic and quality considerations and their selected optimization strategies that favour the production of potential bioactive molecules were also reviewed.

Abstract Background: Analysis of different type of consolidation in dogs and cats relay on parenchymal and vascular criteria. Hypothesis: the vascular criteria of the consolidation it’s possible to perform in dogs and cats and vascularisation is different in shred, tissue, nodule, wedge sign and mass. Animals: 347 cats and 634 dogs with different types of consolidations. Methods: Retrospective study between 2018-2023. Lung ultrasound performed in dogs and cats with different types of consolidations. Characteristic of bronchogram: air dynamic and static bronchogram, fluid bronchogram or absence of bronchogram. Types of vascularisations in consolidation: tree like type, residual, chaotic vascularisation and penetrating from the chest wall to consolidation and “vascular sign”. Conclusion and Clinical Importance: Analysis of bronchogram and type of vascularisation in consolidation is possible to perform in dogs and cat. The analysis of mentioned criteria had an impact on subsequent diagnostic and therapeutic decisions

The occurrence of potential spikes in a cell is a sign of life, and it is called action potential. There is a common notion that neuron signal conduction is the conduction of action potential. Hence, action potential is a typical and essential life activity. However, such potential spikes occur even in simple nonliving systems. According to the experimental observations by Pollack, structured water molecules can generate a negative potential environment. From this observation, the potential spike generation process for both living and nonliving systems caused by ion and water molecule adsorption-desorption process could be explained in this paper. So, taking into consideration the electrically neutral water molecules,the action potential generation mechanism could be explained. It is a fully inanimate model. Hence, the action potential may not be a life activity. Here, the role of water molecules in life is investigated further. It was found that the phase transition of the membrane is involved in the neuron signal conduction, but the membrane phase transition could be due to the change of state of the water molecules, which forms a large-scale structure in the cavities created by a number of lipids.

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

The malaria parasite resides within erythrocytes during one stage of its life cycle. During this intraerythrocytic period, the parasite ingests the erythrocyte cytoplasm and digests approximately two-thirds of the host cell hemoglobin. This digestion occurs within a lysosome-like organelle called the digestive vacuole. Several proteases are localized to the digestive vacuole and these proteases sequentially breakdown hemoglobin into small peptides, dipeptides, and amino acids. The peptides are exported into the host cytoplasm via the chloroquine-resistance transporter and an amino acid transporter has also been identified on the digestive vacuole membrane. The environment of the digestive vacuole also provides appropriate conditions for the biocrystallization of toxic heme into non-toxic hemozoin by a poorly understood process. Hemozoin formation is an attribute of Plasmodium and Haemoproteus and is not exhibited by other intraerythrocytic protozoan parasites. The efficient degradation of hemoglobin and detoxification of heme likely plays a major role in the high level of replication exhibited by malaria parasites within erythrocytes. Unique features of the digestive vacuole and the critical importance of nutrient acquisition provide therapeutic targets for the treatment of malaria.

How did life begin on Earth? And is there life elsewhere in the Cosmos? Challenging questions, indeed. The series of conferences established by NoR CEL in 2013, addresses these very same questions. The basis for this paper is the summary report of oral presentations that were delivered by NoR CEL’s network members during the 2018 Athens conference and, as such, disseminates the latest research which they have put forward. More in depth material can be found by consulting the contributors referenced papers. Overall, the outcome of this conspectus on the conference demonstrates a case for the existence of “probable chemistry” during the prebiotic epoch.

We review a theory that predicts the onset of thermalization in a quantum mechanical coupled non-linear oscillator system, which models the vibrational degrees of freedom of a molecule. A system of N non-linear oscillators perturbed by cubic anharmonic interactions exhibits a many-body localization (MBL) transition in the vibrational state space (VSS) of the molecule. This transition can occur at rather high energy in a sizable molecule because the density of states coupled by cubic anharmonic terms scales as ~ N3, in marked contrast to the total density of states, which scales as exp(aN), where a is a constant. The emergence of a MBL transition in the VSS is seen by analysis of a random matrix ensemble that captures the locality of coupling in the VSS, referred to as local random matrix theory (LRMT). Upon introducing higher order anharmonicity, the location of the MBL transition of even a sizable molecule, such as an organic molecule with tens of atoms, still lies at an energy that may exceed the energy to surmount a barrier to reaction, such as a barrier to conformational change. Illustrative calculations are provided, and some recent work on the influence of thermalization on thermal conduction in molecular junctions is also discussed.

Based on research data from the renovation of old residential areas in Chengdu, China, this study provides empirical evidence regarding the causal relationship between urban renewal and the transformation of residents' pro-environmental behaviors. The research findings demonstrate a significant enhancement in residents' engagement in pro-environmental behaviors due to the renovation of old residential areas. Robustness tests based on replacement samples and two-stage difference-in-difference models also confirm the reliability of the conclusions. The preliminary mechanism test indicates that the mechanism of the impact of renovation of old residential areas on the transformation of residents' pro-environmental behaviors can be attributed to two main factors. Firstly, the improvement of environmental infrastructure provides residents with better conditions for participating in pro-environmental activities. Secondly, there is an elevation in residents' environmental protection awareness, prompting a more voluntary engagement in pro-environmental behavior. This study suggests that decision-makers should fully recognize that urban renewal activities nationwide are not only a process of improving urban hardware and functionality, but also a realistic and vivid "environmental education" course for the whole nation. Taking urban renewal as an opportunity to enhance citizens' awareness of environmental protection will effectively promote the transformation of pro-environmental behaviors among residents.

Background: Micronutrient deficiencies are common at the time of cancer diagnosis and are associated with worse prognosis. Little is known about them in cancer rehabilitation. Methods: Data from routine health related quality of life (HRQOL) were analyzed at an inpatient cancer rehabilitation center. Rehabilitation patients completed the EORTC QLQ-C30 questionnaire before and after multidisciplinary rehabilitation treatment, and three month after discharge. Selenium and zinc status was measured in whole blood at these three time points. In case of selenium deficiency up to 600 µg selenium per day as sodium selenite was supplemented. Results: A total of 271 patients (breast, colon, and pancreatic cancer) were included in the analysis. There was clinically meaningful improvement in many domains of the EORTC QLQ-C30 during rehabilitation. However, effect often waned in the three months after. Prevalence for selenium deficiency varied between 34 to 90 percent depending on cancer type (breast < colon < pancreas). In contrast, zinc deficiency was rare. Daily selenium supplementation of 600 µg was more efficient to correct selenium deficiency compared to 300 µg selenium per day. Rehabilitation and increasing selenium status after rehabilitation were associated with improved global quality of life, physical and emotional functioning, and fatigue. In cancer patients with decreasing selenium status, values of global quality of life, physical and emotional functioning, and fatigue were back to the values at the beginning of rehabilitation. Conclusions: Selenium deficiency is common in cancer patients admitted to a cancer rehabilitation clinic. Selenium supplementation during rehabilitation effectively corrected selenium deficiency in most cases. The positive effects of rehabilitation persisted longer, when selenium status did not decrease after rehabilitation.

Based on the Graph Model of Conflict Resolution (GMCR), a two-stage decision framework is developed to reveal the essence of brownfield incidents and facilitate the resolution of brownfield conflicts caused by the incidents. More particularly, the forward GMCR is utilized in Stage I, the negotiation stage, to simulate the evolution of a brownfield conflict (BC) and predict its potential resolution via stability analysis. If no acceptable equilibrium can be obtained, the BC progresses into Stage II, the third-party-intervention stage, where the inverse GMCR is used to assist a third party in intervening the conflict to achieve a desirable outcome. To illustrate the practicality of this framework, a recent BC occurred in Changzhou, China, is taken as a case study. Invaluable insights are provided through the computation and investigation of the corresponding preference relationships.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.

A number of chemical modifications were carried out in order to synthesize new compounds based on the triterpenoid betulonic acid. Triazolation reactions were carried out for the synthesis of new 1,2,3-triazole derivatives based on betulonic acid. Chemical changes were made on the carbonyl group at the C-3 position of the initial molecule and on the carboxyl and hydroxyl groups at the C-28 position. Chromatographic methods were used to separate and purify the formed products. Spectroscopic (NMR-, mass-) methods were used to establish the structure of synthesized compounds. As a result of the chemical transformations carried out, a number of new derivatives of betulonic acid were obtained. All synthesized compounds were tested for antimicrobial and cytotoxic activity. As a result, compounds with pronounced antimicrobial activity were identified.

Amongst advantages of using Worldwide Interoperability Microwave Access (WiMAX) technology at the last-mile level as access technology include an extensive range of 50 km Line of Sight (LOS), 5 to 15 km Non-Line of Sight and few infrastructure installations compared to other wireless broadband access technologies. Despite positive investments in ICT fibre infrastructure by developing countries, including Botswana, servicing end-users is subjected to high prices and marginalised. The alternative, the Wi-Fi hotspot initiative by the Botswana government, falls far as a solution for last-mile connectivity and access. This study used OPNET simulation modeller 14,5 to investigate whether Botswana’s national broadband project could adopt WiMAX IEEE 802.16e as an access technology. Several developing countries in Africa and the world use WiMAX technology at access level and gain impressive results. The rampant lack of infrastructure development and the need to provide high-speed technology has necessitated such investigation. Therefore, using the simulation method, this paper evaluates the WiMAX IEEE 802.16e/m over three subscriber locations in Botswana. The results obtained indicate that the deployment of the WiMAX IEEE 802.16e standard can solve most of the deployment issues and access at the last-mile level. Although the findings suggest that WiMAX IEEE 802.16e is more suitable for high-density areas, it could also solve rural areas’ infrastructure development challenges and provide required high-speed connectivity access. However, unlike the Wi-Fi initiative, which requires more infrastructure deployment and less on institutional and regulatory frameworks, the deployment of WiMAX IEEE802.16e requires institutional and regulatory standards.

While immutability is Blockchain's* much celebrated covenant, change is the rule of life. The paradox has seriously limited real-world deployability of Smart Contracts (SC), faltering its mainstream adoption and sustainability. Once implemented, SC remains unstoppable even if its execution makes losses, as evident in the recently exploded $50+B DeFi industry. How do we reconcile the two and make DeFI/Blockchain profitable and sustainable? A DISC (Dynamic Immutable Smart Contract) hypothesis was proposed to resolve the paradox. Using an existing decentralized IoT device framework we test the DISC hypothesis, by designing/implementing a DISC protocol that delivers an algorithmically controlled dynamic off-chain data feed into a self-executing SC. The experiment successfully introduced limited dynamism into SC without compromising its immutability or undermining user control over their SC terms. If consistently reproduced in diverse settings, the DISC protocol could earn an important milestone in the evolution of Blockchain's decentralized economy of the future.

The biophysical consequences of nanoscale curvature have been challenging to resolve due to size-dependent membrane behavior and the experimental resolution limits imposed by optical diffraction. Recent advances in nanoengineering and super-resolution techniques have enabled new capabilities for creating and observing curvature. In particular, draping supported lipid bilayers over lithographically patterned substrates provides a model system for endocytic pits. The experiments and simulations presented below describe the possible detection of membrane curvature through fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), single particle tracking (SPT), and polarized localization microscopy (PLM). FRAP and FCS depend on diffraction-limited illumination and detection. In particular, a simulation of FRAP shows no effects on lipids diffusion due to a 50 nm diameter membrane bud at any stage in the budding process. Simulated FCS demonstrated small effects due to a 50 nm radius membrane bud that was amplified with curvature-dependent lipid mobility changes. However, PLM and SPT achieve sub-diffraction-limited resolution of membrane budding and lipid mobility through the identification of the single-lipid positions with ≤15 nm spatial and ≤20 ms temporal resolution. By mapping the single-lipid step lengths to locations on the membrane, the effects of curvature on lipid behavior have been resolved.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

A numerical application of linear-molecule symmetry properties, described by the D_∞h point group, is formulated in terms of lower-order symmetry groups D_nh with finite n. Character tables and irreducible representation transformation matrices are presented for D_nh groups with arbitrary n-values. These groups are subsequently used in the construction of symmetry-adapted ro-vibrational basis functions for solving the Schrödinger equations of linear molecules as part of the variational nuclear motion program TROVE. The TROVE symmetrisation procedure is based on a set of "reduced" vibrational eigenvalue problems with simplified Hamiltonians. The solutions of these eigenvalue problems have now been extended to include the classification of basis-set functions using ℓ, the eigenvalue (in units of ℏ) of the vibrational angular momentum operator ${\widehat{L}}_z$ . This facilitates the symmetry adaptation of the basis set functions in terms of the irreducible representations of D_nh. ¹²C₂H₂ is used as an example of a linear molecule of D_∞h point group symmetry to illustrate the symmetrisation procedure.

Stem cells are currently being used in many clinical trials for regenerative purposes. These are promising results for stem cells in the treatment of several diseases, including cancer. Nevertheless, there are still many variables which should be addressed before the application of stem cells for cancer treatment. One approach should be to establish well-characterized therapeutic stem cell banks to minimize the variation in results from different clinical trials and facilitate their effective use in basic and translational research.

Epidemiologic studies suggest an inverse correlation between coffee consumption and the occurrence of neurodegenerative diseases, but the role of caffeine and roasting degree are still matter of debate. The objective of this work was to evaluate the effects of caffeinated (light, medium, and dark roast) and decaffeinated instant coffee samples in acetylcholinesterase inhibition and antioxidant assays, as well as in animal models of Parkinson’s disease. Caffeinated coffees inhibited the acetylcholinesterase in much smaller concentrations than decaffeinated coffee. All coffee samples showed antioxidant capacity without relation with the caffeine content. Dopaminergic-like activity in the haloperidol-induced catalepsy test was observed with caffeinated coffee, but not in the decaffeinated sample. The medium roast coffee reduced the number of rotations of rats after methamphetamine administration on the 6-hydroxydopamine unilateral lesion of the medial forebrain bundle. However, the coffee treatment did not avoid the loss of dopaminergic neurons on substantia nigra pars compact and only the smallest dose of coffee was able to avoid the decrease of dopamine levels in the lesioned side of the striatum. Altogether, these results suggest that coffee exerts moderate pro-cholinergic and pro-dopaminergic effects and caffeine seems to be the main responsible for these effects.

Discovery and development of effective strategies to treat emerging and often drug resistant strains of viral and microbial pathogens presents one of the greatest challenges of the 21st century. Despite nearly a century of progress in developments in antimicrobial and antiviral therapies, infectious diseases still account for a substantial proportion of deaths worldwide, including over 100 million globally in the recent pandemic to date. In recent decades, the plague of antimicrobial resistance also represents an additional and alarming signal for both human and animal healthcare and signals a renewed sense of urgency in addressing this issue. This has made the search for novel classes of antibiotics, antivirals and therapeutics found to be capable of bypassing the microbial and viral resistance mechanisms necessary to in order to replenish our current arsenal of antimicrobial and antiviral drugs and update our therapeutic regimens. In addition, the tremendous impact exerted by viral infections and related pathologies on our lives during the recent decade has forced scientists to acknowledge the opportunities and challenges associated with tackling infectious diseases by developing effective antiviral agents endowed with novel mechanisms of action. The discovery of new antimicrobial/antiviral agents, as well as the repurposing of existing drugs and therapeutic options will be crucial to fight the ever-increasing resistance of “superbugs”, pathogenic fungi, viruses, and parasites. Proponents of modern biophoton therapy proposed in this paper can trace its origins to the Russian scientist Alexander Gurwitsch, who a century ago observed ultra-weak emissions of light emerging from an onion root and soon found additional living tissues to be emanating similar energetic phenomena, thus energizing research which continues to the present day and projected toward the development of useful applications of the new-found biological photonic phenomena. The purpose of the present paper is to introduce the past experiences, potential applications and highly successful outcomes of biophotonic therapy as an option to treat infectious diseases including HIV, Hepatitis C, MRSA, and others, with emphasis on efficacy of using biophotonic therapies to treat and ameliorate the drug resistant variants of the above infectious agents, including potential applications for the current COVID-19 pandemic and in preparation for the emergence of the next epidemic or pandemic.

As recently as 2002 programmed aging in mammals was widely thought to be theoretically impossible based on generally accepted concepts regarding the evolution process. However, as described in this article, genetics discoveries, results of selective breeding, and other direct evidence strongly support the idea that aging creates an evolutionary advantage and that therefore complex biological mechanisms evolved that control mammal aging. Like similar life-cycle programs that control reproduction, growth, and menopause the aging program can adjust the aging trait during an individual’s life to compensate for temporary or local changes in external conditions that alter the optimum lifespan for a particular species population. In addition, genetics discoveries strongly support the evolvability concept to the effect that sexually reproducing species can evolve design features that increase their ability to evolve, and that aging is one such feature.

Abstract: Kiwifruit, a perennial horticultural crop known for its nutritional value, faces significant challenges due to biotic and abiotic stresses, affecting its yield and quality. Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we investigated the expression patterns of kiwifruit LRR-RLPs under various stress conditions, including pathogen stress, heat stress, waterlogging stress, and copper stress. Through genome and transcriptome analyses, we identified a total of 101, 164, and 105 LRR-RLPs in Actinidia Chinensis 'Hongyang', Actinidia eriantha 'Huate', and Actinidia chinensis 'Red5' kiwifruit, respectively, classified into 9 subgroups based on phylogenetic relationships. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Using RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP genes in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.

Background: Despite continuous improvements in revascularization techniques, refractory angina without potential revascularization options remains a relevant clinical issue with significant impact on patient’s quality of life. Recently, a novel device, the Coronary Sinus Reducer (CSR), has been introduced into clinical practice as a therapeutic option for patients with disabling angina pectoris. In this single-center, observational study, we evaluated the mid-term (3-month) safety and efficacy of the CSR in a real-world cohort. Methods: The study population consisted of 55 patients with refractory angina without potential revascularization options, predominantly men (87.3%) with a high cardiovascular risk factor burden and advanced angina (baseline CCS angina class 3.15 ± 0.6). In terms of procedure safety, all patients underwent successful device deployment with only one periprocedural complication. Results: At the 3-month follow-up we observed statistically significant improvement in angina control measured CCS class and SAQ-7 Total questionnaire along with increased abolition of physical limitation – 6-MWT (233.3 ± 107.1 vs 305.2 ± 126.8; p<0.0001). Additionally, we observed significant improvement in terms of quality of life measurements SF-36, the EQ-5D-5L questionnaire, and the EQ-VAS. Conclusions: Our real-world data suggest that CSR implantation is a relatively safe procedure and appears to be particularly effective in relieving angina symptoms and improving quality of life in subjects with refractory angina.

Faced with increasing climate challenges, this pioneering study introduces groundbreaking approaches to ensure the resilience of potato crops in east-central Poland. Our research aimed to develop an innovative, cost-effective system tailored to the diverse local conditions of this region. Conducted between 2018 and 2020, the study analyzed integrated and organic production systems across different soil types and potato varieties. The experiment was conducted using a randomized block design with three replications in two locations. Integrated practices, enhanced by mineral fertilization and chemical protection, notably delayed the onset of late blight by 16 days and extended the critical infection period by 17% compared to their organic counterparts. Remarkably, the integrated systems resulted in a 49% increase in total production and a 52% increase in commercial yields, demonstrating their effectiveness in enhancing crop resilience. Different potato varieties exhibit varied responses to cultivation systems, influencing both yield and disease resistance. Further investigation into these varietal responses can help optimize cultivation practices, leading to improved efficiency and sustainability in potato farming. Location and soil conditions have a significant impact on potato yield and the spread of potato blight. Further research into specific soil properties and the adaptation of varieties to local conditions can contribute to increased productivity and stability in potato production. This study not only paves the way towards sustainable agriculture but also highlights the crucial role of soil diversity in shaping resilient farming practices.

This study presents a comprehensive approach to trim optimization as a energy efficiency improvement measure, focusing on reducing fuel consumption for one RO-RO car carrier. Utilizing Computational Fluid Dynamics (CFD) software, the methodology incorporates Artificial Neural Networks (ANN) to develop a mathematical model for estimating key parameters such as brake power, daily fuel oil consumption (DFOC) and propeller speed. The complex ANN model is then integrated into a user-friendly software tool for practical engineering applications. The research outlines a seven-phase trim optimization process and discusses its potential extension to other types of ships, aiming to establish a universal methodology for CFD-based engineering analyses. Based on trim optimization results, the biggest DFOC goes up to 10.5% at 7.5m draft and up to 8% for higher drafts. Generally, in every considered case, it is recommended to sail with the trim towards the bow, meaning that the ship’s weight (ballast) should be adjusted to tilt slightly forward.

Twice-exceptional learners face a unique set of challenges arising from the intersection of extraordinary talent and disability. Neurobiology research has the capacity to complement pedagogical research and provide support for twice-exceptional learners. Very few studies have attempted to specifically address the neurobiological underpinnings of twice-exceptionality. However, neurobiologists have built a broad base of knowledge in nervous system function spanning from the level of neural circuits to the molecular basis of behavior. It is known that distinct neural circuits mediate different neural functions, which suggests that 2e learning may result from enhancement in one circuit and disruption in another. Neural circuits are known to adapt and change in response to experience, a cellular process known as neuroplasticity. Plasticity is controlled by a bidirectional connection between the synapse, where neural signals are received, and the nucleus, where regulated gene expression can return to alter synaptic function. Complex molecular mechanisms compose this connection in distinct neural circuits, and genetic alterations in these mechanisms are associated with both memory enhancements and psychiatric disorder. Understanding the consequences of these changes at the molecular, cellular, and circuit levels will provide critical insights into the neurobiological bases of twice-exceptional learning.

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

Molecular transport and quantum tunneling of H2 and H2O molecules through nanoporous gra-phene is studied using computational modeling and first principles density functional theory. It is demonstrated that molecules with sufficiently high kinetic energies can tunnel through the na-nopores. It is also demonstrated that molecules can be trapped in front of the nanopore or behind it. These investigations help us learn the behavior of molecules in and around nanopores of gra-phene. They also help us learn fundamentals of molecular tunneling. We believe, nanoporous gra-phene can play important roles for gas separation and nanofiltration.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

Nodule bacteria (rhizobia) represent a suitable model to address a range of evolutionary prob-lems including the tradeoff between genetic polymorphism and natural selection. Rhizobia possess the complicated genomes in which symbiotically specialized (sym) genes differ in their natural histories from core genes encoding for housekeeping functions. Diversification of sym genes is responsible for the rhizobia microevolution which depends on the host-induced natural selection. For the rhizobia speciation, diversification of core genes is responsible for which the selective factors are unclear. In this paper we demonstrate that in the goats’ rue rhizobia (Neorhizobium galegae) populations collected at North Caucasus and composed of two host-specific biovars orientalis and officianalis (N2-fixing symbionts of Galega orientalis and G. officinalis, respectively), evolutionary mechanisms are different for core and sym genes. In both N. galegae biovars, core genes are more polymorphic than sym genes. In bv. orientalis, evolution of core genes occurs under the impacts of driving se-lection (dN/dS > 1), while evolution of sym genes is close to neutral (dN/dS ≈ 1). In bv. officinalis, evolution of core genes is neutral, while for sym genes, it is dependent on purifying selection (dN/dS < 1). A marked phylogenetic congruence of core and sym genes revealed using the ANI analysis may be due to a low intensity of gene transfer within and between N. galegae biovars. Polymorphism of both gene groups and the impacts of driving selection on the core gene evolu-tion are more pronounced in bv. orientalis than in bv. officianalis reflecting the diversities of re-spective host plant species. In bv. orientalis, highly significant (P0 < 0,001) positive correlation was revealed between the p-distance and dN/dS values for core genes, while in bv. officinalis this cor-relation is lowly significant (0,05 < P0 < 0,10). For sym genes, correlation between the p-distance and dN/dS values is negative in bv. officinalis but is not revealed in bv. orientalis. These data along with the functional annotation of core genes implemented using the Gene Ontology tools sug-gests that evolution of bv. officinalis is based mostly on adaptation for in planta niches while in bv. orientalis evolution presumable depends on adaptation for soil niches. New insights into the tradeoff between natural selection and genetic diversity are presented suggesting that the gene polymorphism may be extended by driving selection only in the ecologically versatile organ-isms capable to support a broad spectrum of gene alleles in their genepools.

Oil-tea (Camellia oleifera) is a woody oil crop whose nectar includes galactose derivatives that are toxic to honey bees. Interestingly, some mining bees of the genus Andrena can entirely live on nectar (and pollen) of oil tea and are able to metabolize these galactose derivatives. We present the first next-generation genomes for five and one Andrena species that are respectively specialized and non-specialized oil-tea pollinators, and combining with published genomes of six other Andrena species which did not visit oil-tea, we performed molecular evolution analyses on genes involved in metabolism of galactose derivatives. Six genes (NAGA, NAGA-like, galM, galK, galT, and galE) involved in galactose derivatives metabolism were identified in the five oil-tea specialized species, but only five (with the exception of NAGA-like) were discovered in the other Andrena species. Molecular evolution analyses revealed that NAGA-like, galK and galT in oil-tea specialized species appeared under positive selection. RNASeq analyses showed that NAGA-like, galK, and galT were significantly up-regulated in the specialized pollinator A. camellia compared to the non-specialized pollinator A. chekiangensis. Our study demonstrated that the genes NAGA-like, galK, and galT had played an important role in the evolutionary adaptation of the oil-tea specialized Andrena species.

In this brief review, the concepts of quantum tunneling and parity violation are introduced in the context of chiral molecules. A particle moving in a double well potential provides a good model to study the behavior of chiral molecules, where the left well and right well represent the L and R enantiomers, respectively. If the model considers the quantum behavior of matter, the concept of quantum tunneling emerges, giving place to a stereomutation dynamics between left- and right-handed chiral molecules. Parity-violating interactions, like the electroweak one, can be also considered, making possible the existence of an energy difference between the L and R enantiomers, the so-called parity-violating energy difference (PVED). Here we provide a brief account of some theoretical methods usually employed to calculate this PVED, also commenting on relevant experiments devoted to experimentally detect the aforementioned PVED in chiral molecules.

Metastasis is the main cause of anti-cancer therapies failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses, relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial to mesenchymal transition (ETM) thus promoting the colonization of distant sites that in turn sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short reviews we will give an overview of the most recent advances related to three main large families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, integrin antagonists and small interfering (siRNAs). Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis.

Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key polyphenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids was the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal and limited human studies for a dual preventative role of OO polyphenols in diabetes and cancer, especially that they share similar risk factors. Putative anti-oxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO phenolics, have produced paradoxical results making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anti-cancer and anti-diabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes.

Infection with Ebola virus (EBOV) is responsible for haemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluc-based protein complementation assay (NPCA) and isolated two compounds disrupting the interaction of the EBOV protein fragment VP35IID with the N terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, we support further testing of the compounds in other species, as well as against further negative sense RNA viruses.

A basic problem in all postulated pathways of prebiotic chemistry is the low concentration which generally is expected for interesting reactants in fluid environments. Even though compounds like nucleobases, sugars or peptides principally may form spontaneously under environmental conditions, they will always be rapidly diluted in an aqueous environment. In addition, any such reaction leads to side products which often exceed the desired compound and generally hamper the first steps of a subsequent molecular evolution. Therefore, a mechanism of selection and accumulation of relevant prebiotic compounds seems to be crucial for molecular evolution. A very efficient environment for selection and accumulation can be found in the fluid continuum circulating in tectonic fault zones. Vesicles which form spontaneously at a depth of approximately 1 km present a selective trap for amphiphilic molecules, especially for peptides composed of hydrophilic and hydrophobic amino acids in a suitable sequence. The accumulation effect is shown in a numeric simulation on a simplified model. Further, possible mechanisms of a molecular evolution in vesicle membranes are discussed. Altogether, the proposed scenario can be seen as an ideal environment for constant, undisturbed molecular evolution in and on cell-like compartments, the latter offering preferential starting conditions for a subsequent RNA world.

Childhood obesity has become a global epidemic, with significant increases in prevalence over recent decades. While excessive calorie consumption and physical inactivity are known factors, emerging research highlights the role of Endocrine-Disrupting Chemicals (EDCs), particularly obesogens, in obesity's pathogenesis. This review explores the historical context of the environmental obesogens hypothesis, their sources, mechanism of action, impact on prenatal and postnatal development and epigenetics. Additionally, it discusses the long-term consequences of childhood obesity and proposes prevention strategies that will mitigate the negative health effects. Obesogens were found to disrupt hormonal balance and metabolic processes through various mechanisms such as altering gene expression, hormonal interference, and inflammation. Especially significant, was exposure during critical windows of development which correlates with increased risk of obesity in childhood or adolescence. Long-term effects of childhood obesity include chronic health conditions and psychosocial issues. A comprehensive approach is necessary to address childhood obesity, encompassing genetic, environmental, and lifestyle factors. Prevention strategies should focus on reducing obesogens exposure, promoting healthy lifestyles, and implementing regulatory policies. Future research should investigate obesogens-diet interactions, microbiome impacts, and combined obesogens effects. Long-term human studies are also crucial for validating findings from animal models and allow for inform decision-making to combat the obesity pandemic.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

This article introduces the Theory of Inverse Discrete Dynamical Systems (TIDDS), a novel methodology for modeling and analyzing discrete dynamical systems via inverse algebraic models. Key concepts such as inverse modeling, structural analysis of inverse algebraic trees, and the establishment of topological equivalences for property transfer between a system and its inverse are elucidated. Central theorems on homeomorphic invariance and topological transport validate the transfer of cardinal attributes between dynamic representations, offering a fresh perspective on complex system analysis. A significant application presented is an alternative proof of the Collatz Conjecture, achieved by constructing an associated inverse model and leveraging analytical property transfers within the inverted tree structure. This work not only demonstrates the theory's capability to address and solve open problems in discrete dynamics but also suggests vast implications for expanding our understanding of such systems.

This article introduces the Theory of Inverse Discrete Dynamical Systems (TIDDS), a novel methodology for modeling and analyzing discrete dynamical systems via inverse algebraic models. Key concepts such as inverse modeling, structural analysis of inverse algebraic trees, and the establishment of topological equivalences for property transfer between a system and its inverse are elucidated. Central theorems on homeomorphic invariance and topological transport validate the transfer of cardinal attributes between dynamic representations, offering a fresh perspective on complex system analysis. A significant application presented is an alternative proof of the Collatz Conjecture, achieved by constructing an associated inverse model and leveraging analytical property transfers within the inverted tree structure. This work not only demonstrates the theory's capability to address and solve open problems in discrete dynamics but also suggests vast implications for expanding our understanding of such systems

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

The highly specialized structure and function of neurons depend on a sophisticated organization of the cytoskeleton, which supports a similarly sophisticated system to traffic organelles and cargo vesicles. Mitochondria sustain crucial functions by providing energy and buffering calcium where is needed. Accordingly, the distribution of mitochondria is not even in neurons and is regulated by a dynamic balance between active transport and stable docking events. This system is finely tuned to respond to changes in environmental conditions and neuronal activity. In this review, we summarize the mechanisms by which mitochondria are selectively transported in different compartments taking into account the structure of the cytoskeleton, the molecular motors and the metabolism of neurons. Remarkably, the motor proteins driving the mitochondrial transport in axons have been shown to mediate also their transfer between cells. This so-named intercellular transport of mitochondria is opening new exciting perspectives in the treatment of multiple diseases.

In this study, we aim to evaluate how cyclodextrin molecules affect the hydrophilicity and selec-tivity of PVDF membrane. Herein, we prepared PVDF-PVP(1-x) β-CDx membranes, with x rang-ing from 0 to 1 wt%. The membranes were deeply characterized by means of X-ray diffraction (XRD), attenuated total reflectance infrared (ATR-IR), Raman spectroscopies, Thermal gravimet-ric analysis (TGA), Contact angle measurement (CA), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The study unequivocally demonstrates the effectiveness of the addition of β-CD molecules on membranes' structural, morphological, and dielectric properties. Adding 0.25wt% β-CD enhanced hydrophilicity, with CA decreasing from 72.6° to 56° and roughness decreasing from 81 to 29 nm. The PVDF-PVP(1-x) β-CDx membranes were then fully characterized using electrochemical impedance spectroscopy (EIS) to determine their dielectric properties, which clearly showed that the presence of β-CD induced polarization of the mem-brane. The separation of various dyes with different sizes and charges was utilized. These dyes included methylene blue (MB, positive, 0.504 nm), methyl red (MR, neutral, 0.487 nm), rose Bengal (RB, negative, 0.588 nm), and brilliant blue (BB, negative, 0.798 nm). Based on our re-search, we found that the membrane's selectivity is determined by both exclusion factors (such as size and dielectric properties) and inclusion inside the β-CD cage. We found that using alpha-CD instead of beta-CD led to the disappearance of dye inclusion. These findings strongly sug-gest that β-CD molecules can be a viable solution for dye removal from wastewater.

Behavior analysis is a widely used non-invasive tool in the practical production routine, as the animal acts as a biosensor capable of reflecting its degree of adaptation and discomfort to some environmental challenge. Predominantly, conventional statistics use occurrence data for behavioral evaluation and well-being estimation, disregarding the temporal sequence of events. The Generalized Sequential Pattern (GSP) algorithm is a data mining method that identifies recurrent sequences that exceed a user-specified support threshold, whose potential has not yet been investigated for broiler chickens in enriched environments. Enrichment aims to increase environmental complexity with promising effects on animal welfare, stimulating priority behaviors and potentially reducing the deleterious effects of heat stress. The objective was to validate the application of the GSP algorithm to identify temporal correlations between heat stress and the behavior of broiler chickens in enriched environments through proof of concept. Video image collection was carried out automatically for 48 continuous hours, analyzing a continuous period of seven hours, from 12:00 PM to 6:00 PM, during two consecutive days of tests for chickens housed in enriched and non-enriched environments under comfort and stress temperatures. Chickens at comfort temperature showed high motivation to perform the behaviors of Preening (P), Foraging (F), Lying down (Ld), Eating (E), and Walking (W) whose sequences &lt;{Ld,P}&gt;; &lt;{Ld,F}&gt;; &lt;{P,F,P}&gt;; &lt;{Ld,P,F}&gt; and &lt;{E,W,F}&gt; were the only ones observed in both treatments. All other sequential patterns (comfort and stress) were distinct, suggesting that environmental enrichment alters the behavioral pattern of broiler chickens. Heat stress drastically reduced the sequential patterns found at the 20% threshold level in the tested environments. The behavior of lying laterally "Ll" is a strong indicator of heat stress in broilers and was only frequent in the non-enriched environment, which may suggest that environmental enrichment provides the animal with better opportunities to adapt to stress-inducing challenges, such as heat.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

Grazing incidence X-Ray Diffraction spectroscopy was employed to characterize crystallinity of Iron, Nickel, Copper and Tungsten, prepared by sparking discharge process in presence of 0.4 T magnetic field at ambient temperature 25 °C. Iron thin film preserved crystallinity even after one year of ageing. Nickel exhibit higher crystallinity when sparked in nitrogen gas flow from the one sparked in oxygen. Tungsten was successfully crystalized after just 40 minutes of sparking inside of magnetic field.

We present a precise and universal method for anticipating the thermodynamic characteristics of polyatomic molecules. Unlike conventional computational approaches that rely on numerous experimental spectroscopy or calorimetry data, our model only utilizes a small number of molecular constants. We accurately predicted the values of entropy, enthalpy, specific heat, and Gibbs free energy for boron trifluoride, which were in excellent accordance with the available experimental data. This investigation introduces a new approach to deal with the anharmonic vibrations of polyatomic molecules

Coating of organic molecules from the solution phase can result in directional crystal growth under certain conditions, even on a smooth isotropic surface and without the need of any kind of graphoexpitaxial preparation of the substrate. Based on reviewing the results from a variety of coating techniques and conditions, we identify the condition that the coating speed should equal the growth speed of the fastest growing crystal plane as crucial for achieving a high degree of directional crystallization.

New setting is introduced to study “closing numbers” and “super-closing numbers” as optimal-super-resolving number, optimal-super-coloring number and optimal-super-dominating number. In this way, some approaches are applied to get some sets from (Neutrosophic)n-SuperHyperGraph and after that, some ideas are applied to get different types of super-closing numbers which are called by optimal-super-resolving number, optimal-super-coloring number and optimal-super-dominating number. The notion of dual is another new idea which is covered by these notions and results. In the setting of dual, the set of super-vertices is exchanged with the set of super-edges. Thus these results and definitions hold in the setting of dual. Setting of neutrosophic n-SuperHyperGraph is used to get some examples and solutions for two applications which are proposed. Both setting of SuperHyperGraph and neutrosophic n-SuperHyperGraph are simultaneously studied but the results are about the setting of n-SuperHyperGraphs. Setting of neutrosophic n-SuperHyperGraph get some examples where neutrosophic hypergraphs as special case of neutrosophic n-SuperHyperGraph are used. The clarifications use neutrosophic n-SuperHyperGraph and theoretical study is to use n-SuperHyperGraph but these results are also applicable into neutrosophic n-SuperHyperGraph. Special usage from different attributes of neutrosophic n-SuperHyperGraph are appropriate to have open ways to pursue this study. Different types of procedures including optimal-super-set, and optimal-super-number alongside study on the family of (neutrosophic)n-SuperHyperGraph are proposed in this way, some results are obtained. General classes of (neutrosophic)n-SuperHyperGraph are used to obtains these closing numbers and super-closing numbers and the representatives of the optimal-super-coloring sets, optimal-super-dominating sets and optimal-super-resolving sets. Using colors to assign to the super-vertices of n-SuperHyperGraph and characterizing optimal-super-resolving sets and optimal-super-dominating sets are applied. Some questions and problems are posed concerning ways to do further studies on this topic. Using different ways of study on n-SuperHyperGraph to get new results about closing numbers and super-closing numbers alongside sets in the way that some closing numbers super-closing numbers get understandable perspective. Family of n-SuperHyperGraph are studied to investigate about the notions, super-resolving and super-coloring alongside super-dominating in n-SuperHyperGraph. In this way, sets of representatives of optimal-super-colors, optimal-super-resolving sets and optimal-super-dominating sets have key role. Optimal-super sets and optimal-super numbers have key points to get new results but in some cases, there are usages of sets and numbers instead of optimal-super ones. Simultaneously, three notions are applied into (neutrosophic)n-SuperHyperGraph to get sensible results about their structures. Basic familiarities with n-SuperHyperGraph theory and neutrosophic n-SuperHyperGraph theory are proposed for this article.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Background: Although the link between environmental lead exposure and several patterns of cardiovascular disease (CVD) has been reported, its association with silent myocardial infarc-tion (SMI) has not been explored. We aimed to assess the association between blood lead levels (BLL) and risk of SMI. Methods: This analysis included 7283 (mean age 56.1±2.52 years, 52.5% women) participants from the Third National Health and Nutrition Examination Survey who were free of clinical CVD. Ascertainment of BLL done using graphite furnace atomic absorption spectrophotometry. SMI defined as ECG evidence of MI without history of MI. Multivariable lo-gistic regression analysis was used to examine the association between SMI and BLL. Results: SMI was detected in 120 participants corresponding to an unweighted prevalence of 1.65%. Par-ticipants with higher levels of BLL had higher prevalence of SMI (0.4%, 0.9%, and 2.4% across BLL tertiles; p-value

Utilizing lignocellulosic biosourced platforms, we synthesized novel cyanostilbene (CS) deriva-tives featuring the 3,4-dimethoxyphenyl moiety. These derivatives were investigated for their emission properties in both solution and solid states. The two simple CS derivatives exhibit very weak luminescence in solution but significant luminescence in the solid state, indicating distinct Aggregation-Induced Emission (AIE) characteristic. Furthermore, combining these two CS units, without conjugation and with quasi perpendicular orientation, results in Dual-State Emission (DSE) fluorophore showing luminescence both in solution and solid states. X-ray crys-tallography studies on the solid-state compounds reveal a structure-emission relationship, demonstrating that the colour emission correlates with the conformations adopted by the mol-ecules in the solid state, which influence the type of stacking.

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence in adult normal tissues and benign lesions. This unique expression pattern positions FAP as a prospective biomarker for targeted tumor radiodiagnosis and therapy. The advent of FAP-based radiotheranostics is anticipated to revolu-tionize cancer management. Among various types of FAP ligands, peptides and antibodies, have shown advantages over small molecules, exemplifying prolonged tumor retention in human volunteers. Within its scope, this review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides, on tumor imaging and therapy. Additionally, it incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

It has been well known for a long time that inert gases, such as xenon (Xe), have significant biological effects. As these atoms are extremely unlikely to partake in direct chemical reactions with bio-molecules, such as proteins, lipids and nucleic acids, there must be some other mode of action to account for the effects reported. It has been shown that the topology of proteins allows for cavities and hydrophobic pockets, and it is through an interaction with such protein structures that inert gases are thought to have their action. Recently, it has been mooted that the relatively inert gas molecular hydrogen (H2), also may have its effects through such a mechanism, and so influencing protein structures and actions. H2 is thought to also act through interaction with redox active compounds, particularly the hydroxyl radical (·OH) and peroxynitrite (ONOO-), but not nitric oxide (NO·), superoxide anions (O2·-) or hydrogen peroxide (H2O2). However, instead of having a direct interaction with H2, is there any evidence that these redox compounds can also interact with Xe pockets and cavities in proteins, so either having an independent effect on proteins or interfering with the action of inert gases. This suggestion with be explored here.

Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 7 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. We focused on articles hypothesizing the identification and study of compounds that induce proliferation and osteogenic differentiation of the two d-DSC populations, representing an interesting issue for regenerative medicine. The reconstruction of bone defects in fact is still a challenge for personalized medicine.

Oxidative stress is an elevated intracellular level of free oxygen radicals that cause lipid peroxidation, protein denaturation, DNA hydroxylation, and apoptosis, ultimately negotiating cells viability. Antioxidants can scavenge such free radicals, thus reducing the oxidative stress and eventually prevent cellular damage. Medicinal plants, fruits, and spices remain the prioritized sources of antioxidants and antimicrobial properties since the time immemorial, but in contrast to plants, microorganisms can be grown at a faster rate under controlled conditions. They are non-toxic, non-carcinogenic, and biodegradable as compared to synthetic antioxidants. Microorganisms including actinomycetes, archaea, bacteria, protozoa, yeast, and fungi are auspicious source of vital bioactive compounds. The list comprises ample of bioactive components from microorganisms. One of them is bacteriocins, which are ribosomally synthesized antimicrobial peptides product of Eurotium sp., Streptomyces parvulus, S. thermophiles, Lactococcus lactis, etc. It has a great potential as next-generation antibiotics targeting the multiple-drug resistant pathogens. Pneumocandins are antifungal lipohexapeptides derived from the fungus Glarea lozoyensis, and inhibit 1,3-β-glucan synthase of the fungal cell wall and act as a precursor for the synthesis of caspofungin. It is widely used against invasive fungal infections and has been recently approved by the FDA. Taxol (paclitaxel), a chemotherapeutic drug derived from the bark of Taxus brevifolia can also be produced by endophytic fungi Taxomyces andreanae and Nodulisporium sylviforme. It is known to inhibit several fungi such as Pythium, Aphanomyces and Phytophthora. Hispidin and its derivate isolated from P. hispidus, reduce inducible nitric oxide synthase (iNOS) expression, obstruct the transcriptional activity of NF-κB, and also decrease the production of reactive oxygen species (ROS) in macrophages. Astaxanthin, known as an “aquatic” carotenoid produced by H. pluvialis, also has excellent ROS quenching activity. This study mainly focuses on fascinating antioxidant and antimicrobial compounds that have been scarcely investigated in microorganisms and discuss the promise and challenges of microorganisms as providers of health benefits.

To resolve the controversial issues of UV-light-initiatedcornealcollagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen riboflavin (RF) concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), riboflavin concentration, diffusion and drops pre-operation and interoperation administration, concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square-root of light intensity, and light dose, respectively. The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.

We conduct a thematic analysis of a U.S. adult sample’s self-reported motives and perception of environmental activists’ motives to engage in pro-environmental behavior via a qualitative online survey. We identified themes using a two-stage coding procedure, whereby the research team first helped to code all content into one or more of 17 inductive content categories, then the lead investigator examined themes in each of the categories and created 5 themes based on both inductive and theoretical (e.g., moral foundations theory) considerations: a) harm and care, b) purity, c) waste and efficiency, d) spreading awareness, and e) self-interest (mostly non-financial). Endorsement of themes were qualitatively similar across individuals’ own self-described motives and perceptions of environmental activists’ motives.

Cellular biomolecular condensates termed ribonucleoprotein (RNP) granules often are enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules is not well understood. In this study, we performed single molecule fluorescence imaging experiments of mRNAs in live cells in the presence of two types of RNP granules, stress granules (SG) and processing bodies (PB), which are distinct in their molecular composition and function. We developed a photobleaching- and noise-corrected colocalization imaging algorithm that was employed to determine the accurate positions of individual mRNAs relative to the granule’s boundaries. We found that mRNAs are often localized at granule boundaries, an observation consistent with recently published data. We suggest that mRNA molecules become spontaneously confined at the RNP granule boundary similar to the adsorption of polymer molecules at liquid-liquid interfaces, which is observed in various technological and biological processes. We also suggest that this confinement could be due to a combination of intermolecular interactions associated with, first, the screening of a portion of the RNP granule interface by the polymer and, second, electrostatic interactions due to a strong electric field induced by a Donnan potential generated across the thin interface.

The neocortex is an exquisitely organized structure achieved through complex cellular processes from the generation of neural cells to their integration into cortical circuits after complex migration processes. During this long journey, neural cells need to stablish and release adhesive interactions through cell surface receptors known as cell adhesion molecules (CAMs). Several types of CAMs have been described regulating different aspects of neurodevelopment. Whereas some of them mediate interactions with the extracellular matrix, others allow contacts with additional cells. In this review, we will focus on the role of two important families of cell-cell adhesion molecules (C-CAMs), classical cadherins and nectins, as well as in their effectors, in the control of fundamental processes related with corticogenesis, with especial attention in the cooperative actions among the two families of C-CAMs.

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Nucleobase-containing molecules are compounds essential in biology due to the fundamental role of nucleic acids, and in particular G-quadruplex DNA and RNA in life. Moreover, some molecules different from nucleic acids isolated from different vegetal sources or microorganisms show nucleobase moieties in their structure. Nucleoamino acids and peptidyl nucleosides belong to this molecular class. Closely related to the above, nucleopeptides also known as nucleobase-bearing peptides are chimeric derivatives of synthetic origin and more rarely isolated from plants. Herein the self-assembly properties of a vast number of structures, belonging to the nucleic acid and nucleo amino acid/nucleopeptide family, is explored in the light of the recent scientific literature. Moreover, several technologically relevant properties such as the hydrogelation ability of some of the nucleobase-containing derivatives are reviewed in order to open the door to future experimental investigations of newly-inspired nucleobase-driven hydrogels. Nucleobase-containing molecules, such as mononucleosides, DNA, RNA, quadruplex (G4)-forming oligonucleotides and nucleopeptides, are paramount in gel and hydrogel formation owing to their distinctive molecular attributes and ability to self-assemble in biomolecular nanosystems with the most diverse applications in different fields of biomedicine and nanotechnology. In fact, these molecules and their gels present numerous advantages, underscoring their significance and applicability in both material science and biomedicine. Their versatility, capability for molecular recognition, responsiveness to stimuli, biocompatibility, and biodegradability collectively contribute to their prominence in modern nanotechnology and biomedicine. In this review, we emphasize the critical role of nucleobase-containing molecules of different nature in pioneering novel materials with multifaceted applications highlighting their potential in therapy, diagnostics, and new nanomaterials fabrication as required in order to address the numerous current biomedical and nanotechnological challenges.

(1) Background: We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules on celiac disease. We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of celiac disease; (2) Methods: CD200, CD200R and Elafin distribution was determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection; (3) Results: We characterized the expression and function of the CD200–CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200, CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type Th1 and Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752, were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD; (4) Conclusions: In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will led to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.

Drug functionalization through formation of hydrophilic groups is the norm in phase I metabolism of drugs for modification of drug action. The reactions involved are mainly oxidative catalyzed mostly by CYP isoenzymes. The benzene ring, as phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e. the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e. the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retaining, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues have been presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design and drug development.

Addressing nautical bottlenecks is crucial to optimize the utilization of inland waterways and maximize economic benefits of transports. To maximize economic benefits, a study was conducted to validate a Key Performance Indicator (KPI)-based framework. This framework offers a structured approach to assess the impact of resolved nautical bottlenecks on the economic benefits of inland waterway transport (IWT). To validate the applicability of the KPI framework, interviews with eleven experts were conducted. The goal was to prioritize each KPI based on their insights. The results of the interviews shed light on the relevance and coherence of both the individual KPIs and the overall KPI framework. The experts confirmed the importance of measures related to transportation efficiency, such as reduced transit times, increased vessel throughput, and enhanced reliability. The validated KPI-based framework serves as a valuable tool for policymakers, industry stakeholders, and researchers. It enables the assessment of the effects of resolving nautical bottlenecks in inland waterway systems. Future research should focus on quantifying the multifaceted impacts, making this framework even more useful for decision-making processes concerning investments in infrastructure upgrades and maintenance.

Introduction: The trophoblast derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. The aim of this study was to establish relationship between concentrations of soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of the fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices were determined in 41 uncomplicated singleton pregnancies. Results: The sHLA-G levels were unchanged both in amniotic fluid and in serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β=0.63, p<0.01). Significant correlation was found between serum sHLA-G level and abdominal measurement (β=0.41, p<0.05) and estimated fetal weight (β=0.41, p<0.05). The amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p<0.01 and VFI: β = -0.44, p<0.01, respectively) were negatively interrelated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p<0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator for placental function, whereas the sHLA-G level in serum can be a prognostic modality for feto-placental insufficiency.

Macrophages are the key effector cells of innate immunity which show two polarized states: M1, classically activated and M2, alternatively activated. Tumor-associated macrophages (TAMs) which usually show M2 polarization, are immunosuppressive cells that enhance tumor metastasis and invasion. Also, enrichment of TAMs is known to be closely associated with poor prognosis of cancer patients. Therefore, TAMs are considered to be promising targets for immunotherapy. Importantly, tumor-derived exosomes emerged as a crucial player in immune regulation which can remodel the tumor microenvironment towards immunosuppressive state. Of note, few studies have shown that exosomes could induce polarization of macrophages towards M2 type in tumor condition, while others showed activation of M1 or mixed phenotype. Considering the role of TAMs in cancer, there is an urgent need to decipher the exosome-mediated cross-talk between tumor cells and macrophages.For this, we used murine model of Dalton’s lymphoma (DL), wherein, firstly, we evaluated increased exosome burden by assessing exosome level in serum as well as in various tissues of tumor-bearing host. Next, proteomic profiling of lymphoma-derived exosomes was done which revealed the presence of immunomodulatory proteins. Of note, these proteins were known to alter the macrophage polarization. In order to assess the effect of these exosomes on macrophages, we performed in vitro study using RAW264.7 cells. In vitro study revealed that frequent uptake of exosomes mediated a morphological change in macrophages which reduced their phagocytic activity. In parallel, exosomes increased reactive oxygen species (ROS) level and inhibited LPS-induced nitric oxide (NO) level in macrophages. Also, exosomes upregulated the expression of arginase-1 (an M2 marker) in macrophages but decreased the LPS-induced nitric oxide synthase 2 (NOS2) (an M1 marker) expression. Moreover, we observed a pro-tumoral cytokine profile in macrophages incubated with exosomes. Our study suggests that exosome load increases in lymphoma-bearing hosts systemically. Importantly, lymphoma-derived exosomes mediate the activation of macrophages towards pro-tumoral M2 type. Our results give an insight into the exosome-mediated tumor and immune cell cross-talk which could serve as an important prospect for targeting in cancer immunotherapy.

In CNS drug discovery, estimation of brain exposure of lead compounds is critical for their optimization. Compounds need to cross the blood-brain barrier (BBB) to reach the pharmacological targets in the CNS. The BBB is a complex system involving passive and active mechanisms of transport and efflux transporters such as P-glycoproteins (P-gp) and breast cancer resistance protein (BCRP), which play an essential role in CNS penetration of small molecules. Several in vivo, in vitro and in silico methods are available to estimate human brain penetration. Preclinical species are used as in vivo models to understand the unbound brain exposure by deriving the Kp,uu parameter, the brain/plasma ratio of exposure corrected with the plasma and brain free fraction. MDCK-mdr1 (Madin Darby canine kidney cells transfected with the MDR1 gene encoding for the human P-gp) assay is the most commonly used in vitro assay to estimate compound permeability and human efflux. The in silico methods to predict brain exposure, such as CNS MPO, CNS BBB scores and various Machine Learning models, help save costs and speed up compound discovery and optimization at all stages. These methods enable the screening of virtual compounds and building of a CNS penetrable compounds library as well as optimization of lead molecules for CNS penetration. Therefore, it is crucial to understand these methods' reliability and ability to predict CNS penetration. We review the in silico, in vitro and in vivo data and their correlation with each other and assess published in silico approaches to predict the BBB penetrability of compounds.

This work considers the task of representation learning on the attributed relational graph (ARG). Both the nodes and edges in an ARG are associated with attributes/features allowing ARGs to encode rich structural information widely observed in real applications. Existing graph neural networks offer limited ability to capture complex interactions within local structural contexts, which hinders them from taking advantage of the expression power of ARGs. We propose Motif Convolution Module (MCM), a new motif-based graph representation learning technique to better utilize local structural information. The ability to handle continuous edge and node features is one of MCM’s advantages over existing motif-based models. MCM builds a motif vocabulary in an unsupervised way and deploys a novel motif convolution operation to extract the local structural context of individual nodes, which is then used to learn higher-level node representations via multilayer perceptron and/or message passing in graph neural networks. When compared with other graph learning approaches to classifying synthetic graphs, our approach is substantially better in capturing structural context. We also demonstrate the performance and explainability advantages of our approach by applying it to several molecular benchmarks.

Many industrial processes, several natural processes involving non-living matter, and all the processes occurring within living organisms take place in solution. This means that the molecules playing active roles in the processes are present within another medium, called solvent. The solute molecules are surrounded by solvent molecules and interact with them. Understanding the nature and strength of these interactions, and the way in which they modify the properties of the solute molecules, is important for a better understanding of the chemical processes occurring in solution, including possible roles of the solvent in those processes. Computational studies can provide a wealth of information on solute-solvent interactions and their effects. Two major models have been developed to this purpose: a model viewing the solvent as a polarizable continuum surrounding the solute molecule, and a model considering a certain number of explicit solvent molecules around a solute molecule. Each of them has its advantages and challenges, and one selects the model that is more suitable for the type of information desired for the specific system under consideration. These studies are important in many areas of chemistry research, from the investigation of the processes occurring within a living organism to drug design and to the design of environmentally benign solvents meant to replace less benign ones in the chemical industry, as envisaged by the green chemistry principles. The paper presents a quick overview of the modelling approaches and an overview of concrete studies, with reference to selected crucial investigation themes.

Climate changes challenges people’s life and sustainability. Environmental problems seem to derive from human behavior. Dentistry has a high environmental footprint that needs to be controlled worldwide. Thus, the change of behavior of dentists is a necessary condition to improve the environmental situation. In this study we use a system dynamics approach to analyze pro-environmental behavior in dentists. Systemic modelling in this case, allow us to make a clear prediction of how the population of non-eco dentists will change in the future if certain factors will be affected and how much time will be needed by the system of a group of dental professionals to become eco- dentists. The ECODENT model was designed with Vensim software. It was based on the influence of WOM (word of mouth) spread of information among colleagues and stakeholders (e.g. patients, auxiliary staff and community) and other factors such as dental income, state support, CaPex and OpEx, education hours, level of urbanization and time to react. By changing each one of them we can observe the changes in the groups of non-eco and eco dentists as well as the flow of the phenomenon. It is tested that by augmenting WOM parameter, state economic support or education hours, while diminishing CaPex and OpEx, changes in pro-environmental behaviors of dentist will be reported in a shorter time. The ECODENT model can be used to further study pro-environmentalism in different dental groups and associations and design relevant eco-friendly educational programs.

LSM4 is an essential yeast gene encoding a component of different LSM complexes involved in the regulation of mRNA splicing, stability and translation. In previous papers we reported that the expression in S. cerevisiae of the K. lactis Lsm4 gene lacking the C-terminal Q/N-rich domain in a Lsm4 null strain S. cerevisiae (Sclsm4D1) restored cell viability. Nevertheless, in this transformed strain we observed some phenotypes which are typical markers of regulated cell death, Reactive Oxygen Species and oxidated RNA accumulation. In this paper we report that a similar truncation operated in the S. cerevisiae LSM4 gene confers to cells the same phenotypes observed with the K.lactis LSM4D1 gene. Up to now there was no evidence on the direct involvement of LSM4 in autophagy. Here we found that the Sclsm4D1 mutant showed defects in the induction of autophagy and it was very sensitive to nitrogen starvation or treatment with low doses of rapamycin, an inducer of autophagy. Moreover, both during nitrogen starvation and ageing, the Sclsm4D1 mutant accumulated cytoplasmic autophagy-related structures, suggesting a role of Lsm4 in Phagophore Assembly Site (PAS) processing and/or vacuolar autophagosome internalization

The prevalence of food allergy has increased in recent years, especially in children. Food allergen avoidance and symptomatic drugs in case of an allergic reaction remain the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanuts, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.

Indoor dusts are collectively formed from anthropogenic and atmospheric activities. Particle matter 10 (PM10) is inhalable and causes significant inflammation by interaction with the pulmonary epithelial barrier. The mediators involved in bronchial epithelial cells response to dust are remined unknown. The air-liquid interface of our lung on chip model was exposed to indoor dust collected from highly polluted houses in Delhi, India. The media were collected after 4 days and cytokine levels were measured. We found that the concentration of IFN, IFNγ, Interleukin-6 (IL-6), IL1b, TNFa, and Granulocyte monocyte colony stimulating factor (GM-CSF) were significantly increased after exposure to indoor dust. IFN type I pathways were a major response from dust exposure. Further investigation is needed to determine the mechanism of action and targets of dust in bronchial epithelial cells.

According to Hofstede’s theory of cultural dimensions, cultures differ in cultural values and norms; values and norms that may influence differences in trendsetting, creative traits and behaviors, and pro-environmental behaviors. Further, because men and women have been socialized within particular cultures, gender differences may exist in trendsetting, creative traits and behaviors, and pro-environmental behaviors. Trendsetters have characteristics that are interrelated with creative traits and behaviors, perhaps inclining them to endorse pro-environmental behaviors. However, the interrelationships among these variables remain unexplored. Thus, the purpose of this study was to examine these three variables among college students in South Korea and the United States, specifically looking at cultural and gender differences. Participants were 225 Korean college students and 221 U.S. college students. Questionnaires included demographic items and scales measuring trendsetting, creative traits and behaviors, and pro-environmental behaviors. Data analyses included descriptive statistics, Cronbach’s alpha reliability, MANOVA, ANOVA and SNK posthoc test. Results show that U.S. (vs Korean) students indicated greater trendsetting and creative traits and behaviors but not greater pro-environmental behaviors. Fashion trendsetting groups in both Korea and the U.S. differed in creative traits and behaviors and pro-environmental behaviors. Among Korean trendsetting groups, reluctant adopters scored lowest on creative traits and behaviors and pro-environmental behaviors. Among U.S. trendsetting groups, trendsetters scored highest on creative traits and behaviors and pro-environmental behaviors; reluctant adopters scored lowest on pro-environmental behaviors. Theoretical and practical implications are provided for researchers and marketers.

This article delves into the pro-cyclicality of Loan Loss Provisions (LLPs) and earnings management, along with equity management, in Portuguese banks against the backdrop of implementing the IFRS 9's Expected Credit Loss (ECL) model. It concentrates on how LLPs mirror economic cycles and financial management practices, providing valuable insights into the operational dynamics of the Portuguese banking sector, marked by distinct economic and regulatory challengesThe research examined a sample of five Portuguese commercial banks, chosen from a group of seventeen in the Portuguese Banking Association. Data spanning from 2013 to 2022 were manually gathered. A multiple linear regression model was employed to scrutinize the relationship between LLPs and variables indicative of economic cycles and the earnings and equity management. The methodology aligns with the approaches of Araújo et al. (2018), Beatty and Liao (2014), and Casta et al. (2019). The analysis indicates a pro-cyclicality in LLPs within the Portuguese context, with a positive response of LLPs to economic indicators like unemployment. Contrarily, the extent of earnings and equity management under the ECL model was less marked compared to the Incurred Credit Loss (ICL) model, suggesting the impact of more stringent regulatory measures. The research corroborates the pro-cyclicality of LLPs in Portuguese banks under the ECL framework, underscoring the necessity for ongoing monitoring and refinement of models for forecasting and recognizing credit losses. The findings point to an area for improvement in financial management practices, despite regulatory enhancements, to promote transparency and ensure financial stability.

The main objective of this paper is to assess pro-environmental behavior, climate change perception, anxiety, hope and despair in different political orientations. Specific aims included to validate all the instruments; to assess whether the factor structure of the scales were valid across political orientations; to evaluate their reliability; to assess differences concerning age, gender and political orientation; to know the variables that explain pro-environment behavior; and to evaluate the moderating role of climate change perception, despair and hope in the relationship between climate change anxiety and pro-environmental behavior. Confirmatory factor analysis (CFAs), multi-group CFAs (to measurement invariance), multiple linear regressions and moderations were performed. Results showed that pro-environment behavior and climate change hope achieved the four levels of invariance across different political orientations; climate change anxiety achieved the three first levels of invariance; climate change perception and climate change despair achieved configural invariance. Climate change anxiety personal experience, climate change perception total, reality and consequences present higher values in left political orientation that in right or center. Climate change anxiety variables contribute most to explaining pro-environmental behaviors. Hope, despair and climate change perception consequences moderate de relationship between climate change anxiety and pro-environment behavior. These results open up new avenues of investigation, namely, to understand why high levels of anxiety lead to more pro-environment al behaviors.

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

Work on callings has burgeoned in the past 20 years, yet recent reviews exposed a lack of conceptual clarity and disagreements around its definition, components and measures. One lingering point of contention revolves around the element of prosociality: Is a calling orientation primarily motivated by self-interest, prosocially orientated, or a mix of both? This conceptual paper reviews and examines the pro-self and prosocial component of a calling outlook, by examining and comparing the ways in which they feature in different calling subtypes: Classic, neoclassic, and modern callings. Our analysis suggests that these subtypes vary in where they are located on a pro-self – prosocial continuum: Classic callings are located on the prosocial side of the axis, modern callings are located on pro-self side of the axis, and neoclassic callings can be situated in the middle of the con-tinuum, integrating self-orientated and other-orientated motivations. Our analysis further suggests that these calling subtypes draw on divergent value systems: Classic callings are propelled by self-transcendent values, modern callings are driven by self-actualization motivations, and neoclassic callings integrate both value systems. We therefore argue that the subjective experiences of pursuing a calling within each subtype pathway differ, alt-hough they may culminate in similar outcomes. The paper offers a novel framework for analyzing people’s calling that draws on their values.

Methane (CH4) has attracted attention as not only synthetic natural gas, but also one of the hy-drogen carriers in terms of energy density. On the other hand, there exist bacterial ecosystems in nature that can decompose organic compounds to produce CH4 and CO2. In this study, Clostridi-um cellulovorans was first cultivated with pig manure (PM) as an unused biomass. Regarding the measurement of organic acids by high-performance liquid chromatography (HPLC), acetate and butyrate were increased in the C. cellulovorans medium containing 0.5% PM, while formate and lactate were decreased in it. Next, in comparison with carbon sources such as glucose, cellobiose, and acetate, cocultivation of C. cellulovorans and Methanosarcina mazei or microbial flora of me-thane production (MFMP) was performed in the C. cellulovorans medium. These results revealed that 0.5% acetate as the sole carbon source produced CH4 only by cocultivating C. cellulovorans and MFMP. Furthermore, MFMP was only cultivated with 1% acetate or 1% methane as a carbon source after precultivated with 0.5% glucose medium for 12 h. As a result, methane productivity of MFMP with 1% methanol medium was approximately eight times higher than that with 1% acetate medium. Finally, next-generation sequencing (NGS) analysis of MFMP after cultivation with 1% acetate or 1% methane was carried out. Interestingly, Methanofollis (0.211%) belonging to H2/CO2 -using methanogens (CO2 reduction pathway) was dominant in the 1% acetate medium for 72 h cultivation, whereas Methanosarcina siciliae (1.178%), M. barkeri (0.571%), and Methano-follis (0.490%) were major species in 1% methanol medium for 72 h cultivation. Since Methano-sarcina spp. are belonging to acetoclasts (acetoclastic pathway), methanol could promote to grow Methanosarcina spp. rather than acetate. Therefore, it seemed Methanosarcina spp. may play a key methanogenesis in MFMP. Thus, these results will provide important information for low cost biomethane production.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing in the world population. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems, as well as regulate the expression of multiple genes and, therefore, proteins involved in starvation-satiety processes, activation of brown adipose tissue, increased lipolysis, decreased lipogenesis, and inflammation, beneficial changes in metabolism and improved insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of the bioactive compound.