The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

Benzo[a]pyrene (B[a]P), is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant and neurotoxicant that contribute to the development of cancer. Microtubules are polymers of tubulin that form part of the cytoskeleton and target for anticancer drugs. Furthermore, NPY significantly increased the percentage of cells in S and G2/M phases. However, little is known about the specific role of NPY in proliferation and the underlying protective mechanism remains unclear. Hence, the aim of this work was to investigate the effect of B[a]P on SH-SY5Y neuroblastoma cells and to explore the potential mechanism for alteration of tubulin-microtubule equilibrium causing mitotic arrest and NPY expression. The present findings showed B[a]P treatment significantly increase number of SH-SY5Y cells in S and G2/M phase as compared to G1 phase and provokes cell cycle arrest that correlated with significant decrease in G0/G1 cells. Immunofluorescence study showed significantly distorted tubulin arrangement from metaphasic plate in formation of bipolar mitotic spindle apparatus. Further, higher doses of B[a]P treatment lead to chromosomal abnormalities accompanied by DNA damage due ROS causing oxidative stress showing significant decrease in tubulin protein around spindle. The results of present study demonstrated that NPY exerts a proliferative and protective effect on B[a]P-induced oxidative stress in a dose-dependent manner in vitro and importantly, these effects may be mediated via mitotic arrest and involved in spindle arrangement during cell division. Our findings addresses a novel pathological outcomes of B[a]P-induced NPY expression by oxidative stress through spindle abnormalities leading to microtubule disruption.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

Polycyclic aromatic hydrocarbons (PAHs), which consist of low-molecular-weight PAHs (LMW-PAHs) and high-molecular-weight PAHs (HMW-PAHs), form an important class of pollutants. Pyrene and benzo[a]pyrene (BaP) are the main pollutants belonging to HMW-PAHs, and their degradation by microorganisms remains an important strategy for their removal from the environments. Extensive studies have been carried out on the isolation and characterisation of microorganisms that actively degrade LMW-PAHs, and to a certain extent, the HMW-PAH pyrene. However, so far, limited work has been carried out on BaP biodegradation. BaP consists of five fused aromatic rings, which confers this compound a high stability, rendering it less amenable to biodegradation. The current review summarizes the emerging reports on BaP biodegradation. More specifically, work carried out on BaP bacterial degradation and current knowledge gaps that limit our understanding of BaP degradation are highlighted. Moreover, new avenues of research on BaP degradation are proposed, specifically in the context of the development of “omics” approaches

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, South Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

This contribution deals with the assessment of air pollution caused by atmospheric aerosol particulate matter fraction PM10 and benzo[a]pyrene (BaP) in the urban agglomeration of Ostrava, located in the Czech Republic in Central Europe. The motivation for this research was the need to identify the sources of air pollution in the area, particularly in locations where the contribution of different sources to concentrations of pollutants of concern has not been elucidated yet. In this study, source apportionment in the vicinity of the industrial hot-spot was performed by statistically evaluating measured pollutant concentrations as a function of meteorological variables and using the Positive Matrix Factorization (PMF) receptor model. A significant methodological innovation and improvement over previous assessments was the higher monitoring resolution of benzo[a]pyrene, with samples collected at three-hour intervals instead of the standard 24-hour collection period. The key findings indicate that in the cold part of the year, secondary particles - specifically sulphates and ammonium nitrates - were responsible for the most significant portion of PM10 air pollution throughout the area of interest. The contribution of these particles ranged from one third to two fifths of the total concentration, except at the industrial site of Ostrava-Radvanice (TORE), where they accounted for approximately one fifth of the measured pollution concentration level. Emissions from individual household heating were identified as the main source of this type of pollution. With regards to benzo[a]pyrene air pollution, the study found that in the whole area of interest, except for the Ostrava-Radvanice site, it mainly originated from individual heating with coal (90%). In contrast, at the Ostrava-Radvanice site, two-thirds of the benzo[a]pyrene pollution came from the premises of Liberty Ostrava a.s., primarily from coke production, and less than one-third from local domestic heating. This study also determined the spatial extent of the occurrence of extremely high benzo[a]pyrene concentrations (above 5 ng/m3), which are estimated to affect nearly 10,000 inhabitants. The results confirm that the data from the TORE station are only representative of its immediate surroundings and are not applicable to the assessment of air quality and causes of air pollution in the whole city of Ostrava or the urban area of Ostrava-Radvanice as a whole. After years of research, these findings provide the Ministry of the Environment of the Czech Republic and the government with an accurate basis for implementing measures to address the identified pollution sources in the area of interest. The success of this study was made possible by the adoption of a more detailed sampling approach, which involved a resolution of 3 hours instead of 24 hours. This methodological improvement is a significant finding and will be useful for future source apportionment studies.

Multilingual classrooms are becoming more common worldwide due to increasing mobility. Teaching foreign languages using the mother tongue in multilingual classrooms has become problematic; some of the significant concerns in Japanese language acquisition – such as the high contextuality of the language, vocabulary and kanji learning – make the direct teaching method confusing for many students, especially at the beginner and elementary levels. This article provides the preliminary results of a study carried out as a component of a more extensive empirical research project on instructional languages in classrooms teaching Japanese as a foreign language. It aims to gather, analyse and synthesise data from a survey conducted at a supranational level. The results of the first two sections of a questionnaire containing closed and open-ended questions were used for a quantitative analysis of the profile of Japanese language instructors with a focus on finding possible connections. The wide geographic distribution of the respondents (274 teachers from fifty-seven countries and regions) made it possible to collect data from a more representative sample and draw meaningful conclusions about the spread of multilingual classrooms that would be impossible in smaller-scale research. The study’s primary results show the proportion of multilingual classrooms among countries in different regions and across different educational stages, the distribution of Japanese language instructors in various educational stages depending on the highest level of formal education attained, and the proportion of part-time instructors working in different academic institutions.

The alkylation of 1,1,2-trimethyl-1H-benzo[e]indole with 2-chloroacetamide, followed by work-up of the reaction mixture with a base and the subsequent treatment of a crude product with acetic acid gives 10a,11,11-trimethyl-10a,11-dihydro-8H-benzo[e]imidazo[1,2-a]indol-9(10H)-one. The structure assignments were based on data from ¹H, ¹³C and ¹⁵N NMR spectroscopy. The optical properties of the obtained compound were studied by UV-vis and fluorescence spectroscopy.

Abstract This study focuses on the toxicity assessment of various flavonoids, with particular emphasis on Hesperidin. Among the investigated compounds, Hesperidin exhibits notable potential and low toxicity in both short and long-term evaluations. The toxicity parameters for Hesperidin include a low Max. Tolerated Dose (Human) (0.525 log mg/kg/day), indicative of its minimal potential harm to humans. Additionally, its Oral Rat Acute Toxicity (LD50) (2.506 mol/kg) suggests a relatively low acute toxicity level. The Oral Rat Chronic Toxicity (LOAEL) (3.167 log mg/kg_bw/day) signifies a higher dose threshold for observing adverse effects over the long term. Furthermore, Hesperidin demonstrates low Minnow Toxicity (7.131 log mM), suggesting minimal impact on aquatic organisms. Overall, this comprehensive assessment positions Hesperidin as a promising flavonoid with favorable properties and minimal toxicity.

The study focused on Molecular Docking simulations using Autodock Vina in conjunction with the Pyrx program to investigate potential drugs and natural compounds against the Bcr-Abl oncoprotein. From initial virtual screening of 200 compounds, 11 potential candidates were selected for further evaluation. Additional investigations included toxicity prediction using the pKCSM server. Among the compounds, Diosmin and Hesperidin showed high maximum tolerated doses in humans and low toxicity. Conversely, only Eltrombopag among the selected drugs exhibited excellent parameters, albeit with a potential risk of liver damage at high dosages. These findings underscore the need for comprehensive evaluation of efficacy and safety in the development of potential treatments targeting the Bcr-Abl oncoprotein.

For the first time, this study identified seven potential ligands with high binding energies through the docking approach against the Crystal Structure of human Melanoma-associated antigen B1 (MAGEB1). The ligands—Imatinib, Bafatinib, Diosmin, Ginkgetin, Bilobetin, Amentoflavone, and Hypericin—showing strong binding energies around -10 kcal/mol, indicate a potentially robust interaction with the target protein. Moreover, the additional step of predicting toxicity properties using the pKCSM server provides valuable insights into the safety profiles of these ligands. From these results, the parameters for Diosmin: —Max. tolerated dose (human),- Oral Rat Acute Toxicity (LD50), and - Oral Rat Chronic Toxicity (LOAEL)—suggest a favorable safety profile, making it a potential candidate for further consideration against Melanoma. Moving forward, it's advisable to conduct further experimental validations, including in vitro and in vivo studies, to confirm the efficacy and safety of Diosmin and other potential ligands. Consideration of pharmacokinetics, metabolism, and specific mechanisms of action will contribute to a comprehensive understanding of these compounds' potential as therapeutic agents.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Although working memory (WM) is crucial for intellectual abilities, not much is known about its brain underpinnings, especially the structural connectivity. We used diffusion tensor imaging (DTI) to look across the whole brain for the white matter integrity correlates of the individual differences in the reading span (verbal WM capacity during reading) in healthy adults. Right-handed healthy native Russian speakers (N = 67) underwent DTI on a 3T Philips Ingenia scanner. Verbal WM was assessed with the Daneman-Carpenter reading span test (Russian version). Fractional anisotropy maps from each participant were entered into the group tract-based spatial statistics analysis with the reading span as a covariate; the results were TFCE-corrected. After taking into account effects of age, sex, education and handedness, reading span positively correlated with the white matter integrity in multiple sites: the body, the genu and the splenium of corpus callosum; bilateral corona radiata (anterior, posterior, and superior); bilateral superior longitudinal fasciculus; several tracts in the right hemisphere only, including the internal and external capsule; bilateral superior parietal and frontal white matter. Although the left hemisphere is central for verbal processing, we revealed the important role of the right hemisphere white matter for the verbal WM capacity. Our finding indicates that larger verbal working memory span may originate from additional processing resources of the right hemisphere.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

This study focused on the investigation of myeloperoxidase through a Molecular Docking approach with various natural compounds to identify potential substances for cardiovascular research. Recent research has linked elevated myeloperoxidase levels to the severity of coronary artery disease. The results of the docking analysis revealed Polydatin, Daidzin, Astringin, Ginkgetin, and Amentoflavone as promising compounds with excellent binding capacity. To complement this, toxicity prediction studies were conducted using pkCSM. Overall, all four investigated molecules (Amentoflavone, Daidzin, Ginkgetin, and Astringin) were found to be non-toxic, exhibiting high maximum tolerated doses (human) and favorable values for Oral Rat Acute Toxicity and Oral Rat Chronic Toxicity. Moreover, they showed non-AMES toxicity and non-hepatotoxicity. Astringin, in particular, stood out with the highest positive effects, including a high maximum tolerated dose (human) and favorable values for Oral Rat Chronic Toxicity, along with dual inhibition of hERG II and hERG I. These findings suggest the potential utility of these compounds in cardiovascular research with minimized unwanted effects.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

The NP method was used to elucidate the contributions of vehicles and coal combustion to seasonal and long-term atmospheric PM-bound Pyr and 1-NP concentrations in Kanazawa, Kitakyushu, Shenyang, and Shanghai in the Western Pacific region from 1997 to 2021. Among the four cities, Kanazawa demonstrated the lowest Pyr concentration. The contribution of vehicles to Pyr before and after 2010 were 35% and 5%, respectively. The 1-NP concentration reduced by a factor of more than 1/10. These changes can be attributed to the emission control from vehicles. Kitakyushu revealed the second lowest Pyr and the lowest 1-NP concentrations. Coal combustion was found to be the main contributor to Pyr, while its contribution to 1-NP increased from 9% to 19%. The large contribution of coal combustion is attributed to iron manufactures. Shenyang demonstrated the highest atmospheric Pyr concentration with its largest seasonal change. Vehicles are the largest contributors to 1-NP. However, coal combustion, including winter coal heating, contributed 97% or more to Pyr and more than 14% to 1-NP. Shanghai revealed the second highest Pyr and 1-NP concentrations, but the former was substantially lower than in Shenyang. Coal combustion was the major contributor, but the contribution of vehicles to Pyr was larger before 2010 similar to Kanazawa.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

The objective of this study was to detail the monomer composition of resin-based dental materials sold in the market in 2023 and to evaluate the proportion of BPA derivatives in relation with their applications. A search on manufacturers’ websites was performed to reference resin-based dental materials currently on the market. Their monomer composition was determined from material safety data sheets and completed with a search on PubMed database. Among the 543 material compositions exploitable, 382 (70.3%) contained BPA derivatives. Among them, 56.2% contained BisGMA, 28% BisEMA, the most frequently reported. A total of 59 monomers of which 6 BPA-derivatives were found. 309 materials (56.9%) contained UDMA and 292 (53.8%) TEGDMA. Less than one third of materials identified contained no BPA derivatives. These proportions vary a lot depending on their applications with materials dedicated to dental care of young populations containing the highest proportions of BPA-derivatives monomers. The long-term effects on human health of the different monomers identified including BPA-derivatives monomers is a source of concern. For children and pregnant or lactating women arises the question to take a precautionary principle and avoid the use of resin-based dental materials likely to release BPA by opting for alternative materials.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

Inflammation is a cause of number of disorders. Many anti-inflammatory drugs are available to cure and prevent inflammation and its related disorders. Some of the drugs are from plant and animal origin. Among animals snake venom is also utilized as treatment option of certain disorders. In the current study the venom of N. oxiana from Northern areas of Pakistan is assayed to determine its anti-inflammatory activity. The Naja oxiana is also called central Asian cobra is endemic to Central Asia. Naja oxiana belong to family Elapidae and it is highly venomous snake. The venom has many enzymatic proteins as well as nonenzymatic proteins that is neurotoxins. The venom is lethal having very high mortality rate and the death may occur due to respiratory failure in 45 minutes to 24 hrs depending upon the nature and amount of venom. As the venom is highly toxic so initially after venom milking its protein estimation was done and toxicity profile and LD50 was determined to find out its therapeutic dose at which anti-inflammatory activity was observed. The toxicity and anti-inflammatory activity was determined on mice model. Inflammation was induced by carrageenan induced peritonitis method. The inflammatory markers ROS, TNF-α and IL-β were determined by ELIZA in peritoneal fluid. The LD50 of crude venom, fraction 1 and fraction 2 was found as 34 µg/kg, 7.4 µg/kg and 416 µg/kg respectively. Anti-inflammatory activity crude venom, fraction 1 and fraction 2 was found at dose 19 µg/kg, 1.8 µg/kg and 267 µg/kg respectively. The levels of inflammatory markers reduced after therapeutic dose administration of venom and its fractions that indicates that it can be utilized as anti-inflammatory agent and so can be effective in various disorders.

Spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real time proliferation assay. Comet assay was used to determine oxidative damage of UCNPs. In vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. Proliferation assay revealed that L-UCNPs were less toxic than S-UCNPs. The viability of rat mesenchymal stem cells (rMSCs) incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. Oxidative damage measured by the Comet assay showed that neat L-UCNPs caused oxidative damage to rMSCs more than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.

Improper lifting measures of long-span spatial steel structures during construction process may delay the construction period and even cause safety accidents. Few studies on long-span spatial steel structures considered time-varying mechanical characteristic during construction process. In order to achieve safe and efficient installation in a long-span spatial steel structure, this research presents a time-varying mechanical analysis of the synchronous and asynchronous integral lifting and a single and interlaced point’s asynchronous integral lifting analysis method of a long-span spatial steel structure. The results showed that in the case of asynchronous lifting of single point, the displacement influence on other members is related to the distance. The closer the distance from the lifting point, the greater the influence. In asynchronous integral lifting, the lifting point with large lifting force is first installed to the specified position, and the lifting point with small lifting force is installed to the specified position.

Nanoparticles (NPs) are widely used in diverse disciplines, including biology, medicine science. The central question that need to be answered is whether NPs have toxic effects on biological cells and molecules or are they safe. The safety of NPs including targeted drug delivery is critical and so is their toxicity in the environment. In recent years, in vitro and in vivo research on animals has generated abundant information about the toxicity of NPs. However, due to varying laboratory conditions, the comparison of the results from ensuing studies is somewhat unreliable. It should be noted that, depending on the type of production, NPs can enter the body through inhalation, skin and via digestive routes. Due to the diversity of NPs and their properties, there is paucity of accurate information on their toxicological effects; particle size, shape, surface area and the chemical levels are considered as key factors in creating health and toxicological effects. Consequently, there is a need for reliable information about their effects on various organs so as to deal with NPs effectively and their impact on health and the environment. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

This study explores the potential of natural compounds, including Daidzin, Luteolin, and Silibinin, as inhibitors of human monoamine oxidase B (MAO-B) for the treatment of Parkinson's disease. Docking simulations were performed using Autodock Vina with Pyrx program to evaluate the binding affinities of these compounds with MAO-B. Results indicate that Daidzin, Luteolin, and Silibinin exhibit promising binding affinities with MAO-B, with Daidzin demonstrating the highest affinity. Toxicity parameters were further predicted using the PkCSM Server, confirming the low toxicity of these compounds. Overall, the findings suggest that Daidzin, Luteolin, and Silibinin have the potential to be effective and safe treatments for Parkinson's disease through their inhibition of MAO-B. Further experimental validation is warranted to support their therapeutic efficacy in clinical settings.

Epoxy asphalt (EA) concrete is widely used in constructing long-span steel bridge pavements (SBDPs). This study aims to derive a fatigue damage evolution law, conducting an experimental investigation of SBDP. First, a general theoretical form of the fatigue damage evolution law of materials is established based on the thermal motion of atoms. Then, fatigue experiments demonstrate that this evolution law well represents the known damage–life relationships of SBDP. Taking into account the experimental relationships between damage and fatigue life under symmetrical cyclic loadings with different overload amplitudes and temperature variations, a detailed damage evolution law is deduced. Finally, the role of damage accumulation is discussed on the basis of the proposed damage evolution law for the extreme situation of heavy overload and severe environments. The results show that both heavy loading and falling temperatures increase the fatigue damage of SBDP considerably; therefore, SBDP should avoid heavy loading combined with winter temperatures. EA shows a fatigue life two to three times longer than that of modified matrix asphalt (SMA) or guss asphalt (GA). For the same thickness, EA pavement is demonstrated to be more suitable for an anti-fatigue design of large-span SBDP under high traffic flows and low temperatures.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Artificial intelligence (AI) has emerged as a powerful tool for addressing the challenges posed by climate change and their impact on public health. By leveraging its capacity to analyze and predict climatic patterns, AI offers opportunities to enhance resource management and develop effective strategies for climate change mitigation. Moreover, AI can contribute to generating sustainable solutions that address the complex and interconnected nature of climate change. For example, AI can enable the optimization of energy consumption and facilitate the integration of renewable energy sources into existing systems. It can also support the development of climate models that provide timely and accurate predictions, enabling policymakers to implement proactive measures for disaster preparedness and response. Furthermore, AI-powered disease surveillance and mitigation techniques can improve public health outcomes by identifying patterns and trends in the spread of diseases in relation to climatic factors.However, the widespread adoption of AI-based solutions is not without challenges. Ethical concerns surrounding privacy and data ownership must be addressed, as the use of AI requires access to large datasets, raising potential privacy risks. Technical constraints, such as limited computational power and the need for sophisticated algorithms, also pose obstacles to the implementation of AI in climate change mitigation strategies. Furthermore, issues related to the accessibility and affordability of AI technologies must be resolved to ensure equitable distribution and maximize its potential impact on public health.To fully harness the power of AI in addressing climate change and improving public health outcomes, it is crucial to promote innovation, multidisciplinary collaboration, and open data science. Innovation can drive the development of new AI algorithms and technologies specifically tailored to address climate change challenges. Multidisciplinary approaches that bring together experts from diverse fields, including climate science, public health, and computer science, can foster a holistic understanding of complex systems and enable the design of comprehensive solutions. Finally, open data science practices, such as sharing data and algorithms, can facilitate collaboration and accelerate progress in mitigating climate change and its public health impacts.In conclusion, AI offers promising opportunities for effectively addressing climate change and its impact on public health. However, to fully realize its potential, it is essential to tackle ethical and privacy concerns, overcome technical constraints, and ensure accessibility and affordability. By promoting innovation, multidisciplinary collaboration, and open data science, we can unlock the transformative power of AI in mitigating climate change and improving public health outcomes.

BPA is a commonly used compound in many industries and has versatile applications in polycarbonate plastics and epoxy resins production. BPA is classified as endocrine-disrupting chemical which can hamper fetal development during pregnancy and may have long term negative health outcomes in humans. Dietary sources, main route of BPA exposure, can be contaminated by the migration of BPA into food during processing. The global regulatory framework for using this compound in food contact materials is currently not harmonized. This review aims to outline, survey, and critically evaluate BPA contamination in meat products, including level of BPA and/or metabolites present, exposure route, and recent advancements in the analytical procedures of these compounds from meat and meat products. The contribution of meat and meat products to the total dietary exposure of BPA ranges between 10 and 50% depending on the country and exposure scenario considered. From can lining materials of meat products, BPA migrates towards the solid phase resulting higher BPA concentration in solid phase than the liquid phase of the same can. The analytical procedure is comprised of meat sample pre-treatment, followed by cleaning with SPE, and chromatographic analysis. Considering several potential sources of BPA in industrial and home culinary practices, BPA can also accumulate in non-canned or raw meat products. Very few scientific studies have been conducted to identify the amount in raw meat products. Similarly, analysis of metabolites and identification of the origin of BPA contamination in meat products is still a challenge to overcome.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3′-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

The brain being arguably the most complex organ in the human body, its detailed functioning is yet to be fully deciphered, let alone accurately modeled. Nonetheless, the medical community has gathered quite a remarkable amount of studies about the consequences of illnesses and injuries on its development and functioning. This bibliographic review aims to cover mostly the findings related to the changes in the physical distribution of neurons and their connections - the connectome -, both structural and functional, as well as their modelling. It does not intend to offer an extensive medical description of all injuries and diseases affecting the brain, rather presenting the most common ones succinctly so the need for accurate brain modelling can be fully understood and pondered, offering propositions to this aim.

In this article, we describe a simple procedure for evaluating the sterility of nutrient media using a shear-horizontal surface acoustic wave (SH-SAW) biosensor. We used the SH-SAW biosensor platform to monitor the time-dependent phase responses of the material for the media that binds to a monolayer of 3-mercaptopropanyl-N-hydroxy succinimide on the biosensor surface. Increases in the phase shift less than 50% of the starting phase shift recorded 180 minutes after the sterilization indicate a successful sterility test of the media. Our devices were then applied to sterility testing using a viable Escherichia coli (E. coli) K-12 solution to confirm our hypothesis. Filtered LB Broth was the negative control, and a 24-hour culture of E. coli was the positive control. Before testing, the cell solution was pelleted, the media decanted and then replaced with a 1x phosphate-buffered saline solution (1x PBS). Since we know that the N-hydroxysuccinimide residues will bind to amine groups, only in cases where microbial species are present will the surface binding increase greater than 50%. We confirmed our hypothesis using SH-SAW biosensors and overnight E. coli cultures. The sensitivity for our 250 MHz quartz SH-SAW sensors was calculated based on the response from the E. coli K-12 solution over the linear dynamic range, which appears to be 2x104 – 2x107 CFU per ml and has a sensitivity of S = 1.655x105 o m2 Kg-1. The limit of detection (LOD) for these sensors was calculated to be approximately 2x10-9 grams (g) which is estimated to be approximately 2,000 Escherichia coli (E. coli) K-12 cells. However, the sensitivity and insertion loss remained approximately unchanged before and after coating the sensor with 3,3'-Dithiobis(succinimidyl) Propionate (DSP).

Glioblastoma (GBM) is a major type of primary brain tumors without ideal prognosis and it’s necessary to find novel compound possessing therapeutic effect. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates apoptosis of neuroglioma cells is unclear.The present study was to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates apoptosis of neuroglioma cells. Briefly, The an-ti-glioblastoma activity was assessed in human glioma U87 xenografts nude mice. Chr-A-related targets were identified by RNA-seq. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed by flow cytometry. Apoptosis-related proteins and possible molecular mecha-nism were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografts nude mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathway were involved in the possible mechanism. Chr-A increased apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blot revealed that Chr-A broke the balance between Bax and Bcl-2 activating caspase cascade re-action and downregulated the expression of p-Akt and p-GSK-3β, suggesting that Chr-A may contribute to glioblastoma regression modulating Akt/GSK-3β signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

Large-span post-tensioned (PT) beams play a crucial role in maximizing the benefits of post-tensioning techniques. Bonded and unbonded systems are prevalent, with the latter being more widespread in the United States. While bonded systems are advantageous for creating long spans when multiple tendons are grouped in ducts, limited literature exists on their demolition. In a case study, this paper addresses the unique challenge of demolishing large-span bonded post-tensioned beams due to a building's functional change. Emphasizing insights for engineers, it explores the use of cutting and dismantling methods, considering the presence of prestressed cables. The demolition process is distinctive due to the presence of numerous pre-stressed cables along the beams, necessitating a specialized and cautious cutting approach. This is accomplished through the use of a drilling technique that selectively distresses the tendons, ensuring they are not all affected simultaneously. An intriguing observation discussed in this paper pertains to the occurrence of horizontal cracks accompanied by loud sounds following the drilling process, offering insights from the design perspective of PT systems. The paper details an innovative method for safely demolishing large-span bonded PT beams, using ground-penetrating radar and computer models to navigate structural complexities and ensure nearby structures' safety.

Parkinson’s disease (PD) is a neurodegenerative disease that progresses with increasing age and some of its major symptoms include tremor, postural and movement related difficulties. Till date, the treatment of PD remains a challenge because available drugs only treat the symptoms of the disease or possess serious side effects. In light of this, new treatment options are needed, hence this study investigates the neuroprotective effects of an organic Boophone haemanthoides extract (BHE) and its bioactive compounds using an in vitro model of PD involving the toxin 1-methyl-4-phenylpyridinium (MPP+) and SH-SY5Y neuroblastoma cells. A total of seven compounds were isolated from BHE viz: distichamine (1), 1α,3α-diacetylnerbowdine (2), hippadine (3), stigmast-4-ene-3, 6-dione (4), cholest-4-en-3-one (5), tyrosol (6), and 3-hydroxy-1-(4`-hydroxyphenyl)-1-propanone (7). Six compounds (1, 2, 4, 5, 6, 7) were investigated and five showed neuroprotection alongside the BHE. This study gives insight into the bioactivity of the non-alkaloidal constituents of Amaryllidaceae since the isolated compounds and the BHE showed improved cell viability, increased ATP generation in the cells as well as inhibition of MPP+-induced apoptosis. Together, these findings support the claim that the Amaryllidaceae plant family could be a potential reserve of bioactive compounds for the discovery of neuroprotective agents.

The development of gamma rays mutant rice lines would be a solution for introducing variability in already farmer using varieties. In vitro gamma (60Co) mutagenesis reduces chimeras and allows a faster selection of desired traits but requires laboratory process optimization. The objective of the present work was the in vitro establishment of a recalcitrant rice embryogenic calli, the determination of its sensitivity to gamma radiation (Co-60), sequencing MATK and Rubisco for identification purposes, as well as generation optimization. The radiosensitivity of embryogenic calli resulted in an LD50 of 110Gy, while the 20% lethal dose was 64Gy. All sequenced genes matched perfectly with already reported MATK and Rubisco O. sativa genes with a clear SNP that identifies the local variety related to the southeast Asia Region. Callus induction improves with an MS with 2mg/L 2,4D, and the regeneration was achieved with an MS medium with 3mg/L BAP and 0,5mg/L NAA. The optimized radiation condition was 60Gy with an 83% regeneration in a semisolid medium, allowing a balance between mutation and regeneration. When increased to 80Gy, the regeneration rate falls to 29%. An immersion system (RITA®) of either 60 or 120 seconds every 8hours allowed a systematic and homogeneous total regeneration of the recalcitrant line, in contrast with the semisolid medium that resulted in positive but irregular regeneration. Other well-known recalcitrant cultivars, CR1821, CR1113 also had an improving regeneration in the immersion system, demonstrating its potential use for recalcitrant materials. To our knowledge, this is the first report on using an immersion system to allow regeneration of gamma-ray mutants from recalcitrant rice materials.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

Water footprint has been widely used to illustrate the consumption of water in many situations; for instance, in products, processes or regions of interest. In this work, we analyzed – using a sensitivity analysis approach – the effect of some variables in the calculation of the water footprint in the viticulture in Brazilian Serra Gaúcha (the major producing region of Brazilian Wine).The classical Penman-Monteith model for evapotransporation was considered, with uncertainties in some parameters (dead mulch covering fraction in the vineyard, maximum temperatures for some months, altitudes and latitudes of the site). The sensitivity analysis was conducted using the SAFE toolbox under Octave framework. The results indicated that the the portion of the water footprint corresponding to the evapotranspiration is more sensitive to the values of mulch covering fraction and the altitude of the site in comparison with the latitude and the maximum temperatures.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

This study delves into the intricate interplay between cosmology and gravity in dilaton-based models, enhancing our understanding. Exploring boundary theories coupled to gravity, we derive a four-dimensional effective theory from the cosmological constant. Dilaton gravity is then scrutinized, revealing elegant solutions and insights into brane embedding. The analysis extends to probe scalar fields, employing the WKB approximation in both conformal and non-conformal cases. In summary, this work contributes to a nuanced understanding of the complex relationship between cosmology and gravity in dilaton-based frameworks.

Due to the extraordinary mechanical properties of ultra-high-performance concrete (UHPC), the shear stirrups in UHPC beams could potentially be removed. The aim of this study is to determine the effect of beam height and steel fiber volume content on the shear behavior of non-stirrup UHPC beams under a larger shear span-depth ratio (up to 2.8). Eight beams were designed and fabricated, including six non-stirrup UHPC beams and two comparing stirrup-reinforced normal concrete (NC) beams. The experimental results demonstrated that the volume content of steel fiber could be a crucial factor affecting the ductility, cracking strength, and shear strength of non-stirrup UHPC beams and altering their failure modes. Additionally, the height of the beam had a considerable effect on its shear resistance. This study revealed that the French standard formulae were more accurate for the UHPC beams with larger shear span-depth ratios and PCI-2021 formulae greatly overestimate the shear capacity of UHPC beams with larger shear span-depth ratios. Xu’s formulae were more accurate for the steel fiber-reinforced UHPC beams with larger shear span-depth ratios.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

A recent study revealed a persistent presence of the PP-Spike recombinant protein in 50% of individuals who received ModRNA injections, contrasting with unvaccinated controls, whether SARSCoV-2 infected or not, up to 187 days post-injection. The implications of these findings are discussed in the context of PP-Spike recombinant protein-induced hyperimmune/inflammatory reactions and thrombotic vasculitis as mechanisms to elucidate the serious side effects, long-term organ complications, and excess deaths observed after administering Covid ModRNA products. These results underscore the urgent need for a comprehensive reassessment of the risk-benefit profile of ModRNA injections, including an immediate halt in their use for any person, and a renewed emphasis on understanding and addressing their long-term effects on human health

Air pollution has become the world’s single biggest environmental health risk of the past decade, causing about 7 million yearly deaths worldwide. One of the dominant air pollutants is fine particulate matter (PM2.5), a product of combustion. Exposure to PM2.5 has been associated with decreased lung function, impaired immunity, and exacerbations of lung disease. Accumulating evidence suggests that many of the adverse health effects of PM2.5 exposure are associated with lung inflammation and oxidative stress. While the physical structure and surface chemistry of PM2.5 are surrogate measures of particle oxidative potential, little is known about their contributions to negative health effects. In this study, we used functionalized carbon black particles as surrogates for atmospherically aged combustion formed soot to assess the effects of PM2.5 surface chemistry in lung cells. We exposed the BEAS-2B lung epithelial cell line to different soot at a range of concentrations, and assessed cell viability, inflammation, and oxidative stress. Our results indicate that exposure to soot with varying particle surface composition results in differential cell viability rates, expression of pro-inflammatory and oxidative stress genes, and protein carbonylation. We conclude that particle surface chemistry, specifically oxygen content, in soot modulates lung cell inflammatory and oxidative stress responses.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.

Solvents are widely-used in all aspects of chemical sciences. One of the disadvantages of conventional solvents is attributed to the adverse impacts they pose on human health and ecological systems. Emerging class of solvents such as ionic liquids have been proposed to alleviate this problem. In this study, aquatic toxicity and biodegradability of two common industrial solvents are compared to those of two ionic liquids. Results from this study highlight the importance of solvent selection considering the information on the toxicity, biodegradability and fate and transport properties of selected solvents altogether.

Abstract: The expansion of global industries results in the release of harmful volatile acid vapors into the environment, posing a threat to various life forms. Hence, it's crucial to prioritize the development of swift sensing systems capable of monitoring these volatile acid vapors. This initiative holds great importance in safeguarding a clean and safe environment. This paper presents the synthesis and characterization of pyrene-based covalent organic frameworks (COFs) demonstrating exceptional crystallinity, thermal stability, and intense fluorescence. Three COFs—PP-COF, PT-COF, and PE-COF—were synthesized, showcasing large surface areas and robust thermal stability up to 400 °C. The fluorescence properties and intramolecular charge transfer within these COFs were significantly influenced by their Schiff base bonding types and π-stacking degrees between COF layers. Notably, PE-COF emerged as the most fluorescent among the three COFs and exhibited exceptional sensitivity and rapid response as a fluorescent chemosensor for detecting HCl in solution. The reversible protonation of imine bonds in these COFs allowed for the creation of highly sensitive acid vapor sensors, showcasing a shift in spectral absorption while maintaining structural integrity. This research highlights the potential of COFs as reliable and reusable sensors for detecting harmful acid vapors, addressing environmental concerns arising from industrial activities.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. Previously, we developed a sublingual vaccine formulated with the SARS-CoV-2 receptor binding domain antigen and Poly(I:C) adjuvant in nonhuman primates, cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvant and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccineproduced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with Poly(I:C) adjuvant is safe and creates a balanced state of enhancing and suppressing the immune-related response.

Members of the genus Armillaria are widespread forest pathogens against which effective protection has not yet been developed. Due to their longevity and the creation of large-scale cloning of Armillaria individuals, the use of mycoviruses as biocontrol agents (BCAs) against these pathogens could be an effective alternative. This work describes the screening of double-stranded RNA banding patterns as a first approach for potential virus discovery and the use of stranded total RNA-seq for viral detection and characterization in Armillaria spp. collected in the Czech Republic. A total of five single-stranded RNA viruses were detected in Armillaria ostoyae and A. cepistipes, including the first virus of the family Tymoviridae found infecting a member the genus Armillaria and four viruses belonging to the recently described virus group "ambiviruses" with circular ambisense genome organization. Both hammerhead (HHRz) and hairpin (HpRz) ribozymes were detected in all the ambiviricot sequences. Armillaria viruses were compared by phylogenetic analysis and confirmed their specific host by direct RT-PCR, which showed the occurrence of interspecies transmission.

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

PAHs contaminants have toxic, carcinogenic, and even mutagenic properties. Screening bacteria from different sources capable of carrying out the biodegradation of PAHs is important for mapping and mobilization purposes and applying them to polluted hydrocarbon environments. The study aimed to compare the biodegradation power of two types of bacteria isolated from different sources against PAHs. The method applied is the interaction between bacterial suspen-sion and pyrene contaminated waste for 30 days. Biodegradation products in organic compounds were analyzed using GC/MS and FTIR. The analysis results found several indications of the performance of bacterial biodegradation, namely: the aggressiveness of biodegradation of Bl bacteria against pyrene was relatively more dominant than Sb bacteria. The percentage of to-tal bacterial biodegradation for product type Sb was (39.00 %), and that of the product of bacteri-al degradation type Bl (was 38.29 %). The biodegradation products of the test bacteria (Bl and Sb) were relatively similar to pyrene, in the form of alcohol and carboxylic acid organic com-pounds. It was concluded that there was no significant difference in biodegradation per-formance between Bl and Sb bacteria on for pyrene. Both types of bacterial isolates from differ-ent sources can carry out the function of biodegradation of pyrene.

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

The liver diseases are posing serious threat to human health associated with abusive use of allopathy medicines, especially in developing economies like Pakistan. The strengthening of detoxification system using natural products might be a suitable option to minimize the liver problems. In this current research, Zingiber officinale and Azadirachta indica were evaluated for their hepatoprotective role. For the purpose, 20 Sprague Dawley rats were equally divided into four groups i.e., negative control, paracetamol positive control, 2.5% ginger and 2% neem powder, respectively. During 42 days study, the levels of bilirubin and liver enzymes significantly elevated due to liver damage. Although, the values dropped (20-25%) in treatment group. Serum glucose and serum lipid profile increased in positive control group, but reduced (5-10%) in both ginger and neem groups. The serum protein profile declined in liver damage group, however, improved (~5%) in treatment groups. The hematological parameters slightly declined in liver damage group, but increased in ginger and neem groups. Moreover, the white blood cells differential count and renal parameters showed abnormal values in liver damage group, but improved after treatment. This study is promising and highlighted the hepato-protective role of neem and ginger that may open several avenues of research.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.

Polymer inclusion membranes (PIMs), which contained cellulose tri-acetate used as a polymer base, a plasticizer in the form of o-NPOE, and meso-tetra methyl tetrakis-[methyl-2-(4-acetlphenoxy)] calix[4]pyrrole (KP) used as a carrier, were prepared and tested for the effective purification of aqueous solutions of methylene blue dye. The scanning electron microscope (SEM), thermogravimetric analysis (TGA), and attenuated total reflection Fourier transform infrared (ATR-FTIR) were used to define the microstructure and surface of PIMs. Experimental results showed that with the increased concentration of methylene blue in an aqueous solution, the removal percentage also increased. Further observation also showed that the flux increased with the rise of the source phase pH values from 3 to 10. The carrier and plasticizer content in the membrane significantly influenced the membrane’s transport properties. The optimal composition of the membrane in per cent by weight was for KP: 74% plasticizer; 18% support; 8% carrier. It was shown that the membrane with optimal composition showed good reusability and enabled the easy and spontaneous separation of methylene blue from aqueous solutions.

Saikosaponin (SS) a is a compound with various pharmacological properties and easily degraded into SSb1 and SSg in acid condition. In present work another two new degradation products of SSa formed under acid hydrolytic condition were detected and isolated by analytical and semi-preparative liquid chromatography technology, furthermore their structures were characterized as hydroxyl-saikosaponin a and SSb2 by spectral analysis, which is not only essential in stability-indicating method development and validation but also could be used as a worst case to assess the analytical method performance of SSa. Moreover their structural transformation pathways were also proposed.

This article seeks to strengthen efforts in technological developments based on the classification of PET plastic that positively impacts sustainable development and contributes to suitable solutions in collection centers in Mexico. Three experiment designs and machine learning tools for data processing were developed. For the experimentation, three factors were considered: the bottle's size, the amount of liquids inside the bottle, and the label on the bottle. The first experiment was to identify the distance of the sensor from post-consumer PET bottles. The second experiment was to determine the detection ability of the sensor with different levels of liquids inside the bottles, and the third was to determine the detection ability on the bottle labels. A digital lux meter on a microcontroller was developed to monitor illuminance on post-consumer PET plastic when it contains liquid as it passes through a conveyor belt for processing at an average rate of three bottles per second. With the implemented methodology, liquids were satisfactorily detected inside the transparent PET bottles when they had beverages between 25% and 100% of their capacity. Finally, this paper highlights that it is possible to implement an affordable design to identify bottles with liquids for collection centers.

We prove through path integral Monte Carlo computer experiments that the affine quantization of the $\varphi_4^4$ scaled Euclidean covariant relativistic scalar field theory is a valid quantum field theory with a well defined continuum limit of the one- and two-point-function. Affine quantization leads to a completely satisfactory quantization of field theories using situations that involve scaled behavior leading to an unexpected, $\hbar^2/\varphi^2$ which arises only in the quantum aspects.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

This study describes a comparative in vitro study of the toxicity behavior of zinc oxide (ZnO) nanoparticles and micro-sized particles. The study aimed to understand the impact of particle size on ZnO toxicity by characterizing the particles in different media, including cell culture media, human plasma, and protein solutions (bovine serum albumin and fibrinogen). The study used various techniques such as atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to characterize the particles and their interactions with proteins. Hemolytic activity, coagulation time, and cell viability assays were used to assess ZnO toxicity. The results highlight the complex interactions between ZnO NPs and biological systems, including their aggregation behavior, hemolytic activity, protein corona formation, coagulation effects, and cytotoxicity. Moreover, the study indicates that ZnO nanoparticles are not more toxic than micro-sized particles, and the 50 nm particles resulted in general the least toxic. Furthermore, the study found that at low concentrations, no acute toxicity was observed. Overall, this study provides important insights into the toxicity behavior of ZnO particles and highlights that no direct relationship between nanometer size and toxicity can be directly attributed.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

The importance of conflict analysis and safety considerations during work zone intervals at signalized intersections cannot be overstated, as these periods pose unique challenges and safety risks for both motorists and pedestrians. Work zones introduce temporary changes to traffic patterns, lane configurations, and signal timings, which can disrupt the flow of traffic and increase the likelihood of conflicts between vehicles and pedestrians. By conducting comprehensive conflict analysis, it is possible to identify potential conflict points, such as merging areas, pedestrian crossings, and lane transitions, and implement targeted safety measures to mitigate risks. Additionally, considering safety considerations during work zone intervals is paramount to safeguarding the well-being of road users and minimizing the occurrence of conflicts or collisions. Measures such as enhanced signage, temporary traffic control devices, and increased enforcement efforts can help promote compliance with traffic regulations and ensure the safe passage of vehicles and pedestrians through work zones. This study investigates the dynamics of traffic behavior and safety implications within work zones at signalized intersections, aiming to address key challenges and enhance intersection management strategies. Through comprehensive analysis, varying frequencies of Vehicle-to-Vehicle (V2V) conflicts were observed across different movement directions, with significant occurrences identified in specific phases of the traffic signal cycle. Specifically, 69 V2V conflicts in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8 were recorded. Furthermore, the examination of Vehicle-to-Pedestrian (V2P) conflicts underscored the importance of prioritizing pedestrian safety, with notable occurrences observed in phases associated with pedestrian crossing movements. Meanwhile, despite the closure of left-turn movements, instances of red light running persisted, with 69 red light running events in phase #1, 181 in phase #2, 31 in phase #3, 207 in phase #4, 1 in phase #5, 274 in phase #6, 93 in phase #7, and 186 in phase #8.To mitigate these safety concerns during work zone intervals, proactive measures are essential. Strategies include improving communication through clear signage and advanced warning systems, enhancing enforcement efforts with red light cameras and increased police presence, and investing in infrastructure improvements such as temporary pedestrian facilities. Integration of real-time data from sensors, particularly LiDAR technology, offers significant advantages in detecting conflicts and red light runners during work zone intervals. LiDAR's precise, real-time data on vehicle and pedestrian movements, combined with its 360-degree coverage and high spatial resolution, facilitates accurate detection and tracking of potential conflict scenarios, contributing to enhanced intersection safety and traffic management efficiency. This study endeavored to conduct a traffic safety analysis during work zone intervals at a signalized intersection in Baltimore City, known for its high rate of traffic crashes, utilizing LiDAR sensor technology.

The existence of semantic inaccuracy §2 articles by A. Einstein “On the electrodynamics of moving bodies”, illustrating the principle of the relativity of simultaneity. In a sentence “The observers co-moving with the moving rod would thus find that the two clocks do not run synchronously while the observers in the system at rest would declare them synchronous”, the preposition “not” must be moved and placed before the word “synchronous”, at the end of the sentence. The criterion for synchronism of the clocks on the rod is the time it takes for the beam to travel from clock A to clock B and back, and for observers on the rod it will be the same both when the rod is at rest and when the rod is moving. Otherwise, observers on the rod would have had at their disposal an experiment that would allow them to determine whether the rod is moving or at rest, which contradicts the first postulate of the Special Theory of Relativity. The inaccuracy is found unchanged in modern editions in English and Russian, and can become a source of difficulties when teaching the basics of the Special Theory of Relativity based on primary sources, as well as make it difficult to understand the author’s logic when studying independently. Nobel laureate R. Feynman, having expanded and modified A. Einstein's thought experiment, eliminated the inaccuracy described in the article.

Lake sediment records are of great importance for understanding the evolution of watershed environments. Various studies have been carried out to constrain the depositional ages of lake sediments and examine their physical, chemical, and biological characteristics, aiming to construct historical vegetation, environment and climate patterns in Chinese lake watersheds. In this study, we obtained relevant literature on lake sediment records by searching the key word 'age-depth' from the databases – Web of Science and China National Knowledge Infrastructure (CNKI, the largest Chinese academic database). We analyzed the literature based on its type (published in a Chinese/English journal or as a Master’s/PhD thesis), period of publication, journal (if published in a journal), key authors, study area, dating scale, and main aims. The results suggest that the lakes in the plateau regions are the most popular research topic typically covering 100–200 years (short-term) and 500–30,000 years (long-term). The literature focuses on a wide range of topics, from past environmental evolution in the watershed to lake ecology, and provides a solid foundation for better understanding regional climate change and the preservation of lake environments and ecosystems. In the future, resulting data from environmental reconstruction with lake sediments will be needed to integrate with emerging information processing technologies (e.g., artificial intelligence and meta-analysis), to disentangle the complex interplay between Earth surface processes and global climate change; furthermore, strengthening interdisciplinary collaboration will deepen our comprehension of man-land relationship and promote the sustainable management of lake ecosystems in the context of global climate change.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

In the dynamic landscape of the telecommunications industry, understanding and mitigating customer churn is paramount for maintaining competitive advantage and sustaining revenue streams. This comprehensive literature review delves into the intricacies of customer churn prediction, a crucial aspect in fortifying the bond between telecom businesses and their customers. The review methodically analyzes 11 articles published between 2000 and March 2024, spotlighting the strategic role of Customer Relationship Management and the prevalence of high churn rates that necessitate a shift from customer acquisition to retention strategies. Furthermore, the review navigates through the challenges inherent in churn prediction, including the complexities of managing large, imbalanced, and noisy datasets and the intricacies involved in model selection and optimization. Despite these challenges, the paper highlights the superior capability of machine learning techniques in handling complex datasets to provide accurate predictions, albeit acknowledging their practical complexities. The main aim of the study is to provide an overview, serving as a knowledge base for researchers interested in machine learning techniques within the realm of telecommunications.

In this paper, we proposed the fusion of two projection based face recognition algorithms: local binary Patterns in DCT domain and singular value decomposition (SVD) characterized by its simplicity and efficiently. Standard databases ORL are used to test the experimental results which prove that proposed system achieves more accurate face recognition as compared to individual method.

With the ongoing amendment of the EU legislation on the treatment of urban wastewater, stricter requirements for the removal of pollutants are expected, which calls for the need for innovative wastewater treatment technologies. Biological systems are still the first choice. The survey of typical bioreactors applied in wastewater treatment is presented. Wastewater treatment objective, bio-chemical environment and microbial growth are selected as a main criterion for classification of these bioreactors. Hydraulic and kinetic aspects are considered, advantages and drawbacks of these bioreactors regarding the selection of appropriate type of the reactor as well as regarding operation of reactors are mentioned. The aim of this paper is to provide operators and designers with a brief overview of selected traditional and advanced processes, reactors, and technologies for nutrient removal from municipal wastewater. Another goal is to discuss the possibilities and limitations to comply with more strict effluent standards. From the evaluation of the published papers, it follows that the currently applied traditional methods of nutrients removal have the potential to convey also with the expected stricter limits.

This study provides a comprehensive comparison of the Peter Chew Sum method and Newton's Sum in Quadratic Root Function Computations. Both methods offer significant advancements by alleviating the need for memorization of multiple formulas. However, when confronted with higher-order quadratic root functions such as the calculation of power 33. Newton's Sum method proves cumbersome due to its requirement of all previous answers for final computation, leading to increased steps and error risks. In contrast, the Peter Chew Sum method simplifies the computational process by requiring only a few previous answers, resulting in a more straightforward series of operations. We contextualize our analysis within the historical progression of mathematical techniques, highlighting the transformative leap represented by the Peter Chew Sum method in quadratic root function computations. Peter Chew Sum addressing the limitations of Newton's Sum , especially concerning higher-order functions such as the calculation of power 256. Furthermore, study demonstrates that the innovative approach of the Peter Chew Sum method not only simplifies complex computations but also fosters enhanced conceptual understanding among students. In conclusion, study findings underscore the profound impact of the Peter Chew Sum method on quadratic root function computations.

The ordinary 3D wave equation for nondissipative, homogeneous, isotropic media admits solutions where the point sources are permitted to move, but it does not admit solutions where the receiver is allowed to move. To overcome this limitation, the new wave equation is derived, permitting both the receiver and the source to move. This new wave equation is a generalization of the standard wave equation, and it reduces to the standard wave equation when the receiver is at rest. To derive this new wave equation, we first mathematically define a diverging spherical wave caused by the stationary point source. From this purely mathematical definition, the wave equation for the stationary source and the moving receiver is derived together with the corresponding free-space Green's function. Utilizing the derived Green's function, it was shown that this new wave equation also permits the solutions where both the receiver and the source are permitted to move. In conclusion, this paper demonstrates that, instead of an ordinary wave equation, the wave equation for the moving source and the moving receiver governs the waves emitted by the moving point sources and received by the moving receivers.

This study employs molecular docking techniques to investigate a spectrum of targets within Escherichia coli (E. coli), with a specific focus on four key proteins: Beta-lactamase, MccE protein, Penicillin G acylase, and DNA polymerase II. The research explores the binding interactions of various natural compounds, emphasizing Hypericin. Through computational analyses, the study aims to unveil the potential interactions between these compounds and essential proteins in E. coli. Notably, Hypericin demonstrates remarkable binding energy scores of approximately -10.5 kcal/mol within the Ligand Binding Site of the specified proteins. This observation suggests Hypericin's potential as a potent modulator of E. coli targets, prompting further investigation into its antimicrobial properties and therapeutic applications.

Coastal resources in Lian, Batangas, have undergone significant degradation due to a combination of human activities and natural factors, including sea-level rise, changes in sea-surface temperature, fluctuations in rainfall, increased storm frequency, and sedimentation. This has led to adverse effects on key ecosystems such as corals, mangroves, and seagrasses. To assess the extent of climate change hazards on these coastal resources, a Vulnerability Assessment was conducted in the municipality of Lian, Batangas. The assessment employed a combination of the Coastal Integrity Vulnerability Assessment Toolkit (CIVAT) and Integrated Coastal Sensitivity, Exposure, and Adaptive Capacity to Climate Change (ICSEA-C) guidelines. Additionally, the analysis incorporated detailed mapping using Light Detection and Ranging (LiDAR) data for mangroves and LandSat 8 imagery for corals and seagrasses. The findings at the municipal scale revealed that a staggering 90% of mangroves in Lian, Batangas, were highly vulnerable. This vulnerability was attributed to a high score in intrinsic characteristics and a low adaptive capacity. Similarly, a majority of seagrasses in the area were classified as medium and highly vulnerable at the municipal level. Only 10–20% of seagrasses received low to medium vulnerability scores. Shockingly, almost 100% of the coral reefs in Lian, Batangas, were deemed highly vulnerable, indicating a critical threat to this crucial marine ecosystem.

Despite the recognized influence of maximum or acceleration strength on combat techniques and countermovement jump (CMJ) performance, the relationship between body segment weights and combat techniques remains unexplored. This study aimed to examine the impact of body segment weights, including striking arm weight (SAW), kicking leg weight (KLW), and trunk weight (TW), on the dynamics of direct punches (DP), palm strikes (PS), elbow strikes (ES), front kicks (FK), and CMJ performance. Sixteen male military cadets (22.3±1.8 years, 181.4±7.0 cm, 83.0±8.1 kg) performed combat techniques, with performance measured by using a force plate and body segment weights assessed by Dual-energy X-ray absorptiometry. Spearman's correlation analysis was applied. Results indicated a strong correlation between KLW and FK impulse (r = 0.64, p ≤ 0.01) and CMJ impact force (r = 0.80, p ≤ 0.01). SAW showed moderate correlations with DP impulse (r = 0.53, p ≤ 0.05) and ES impulse (r = 0.54, p ≤ 0.05). Additionally, FK peak and impact forces were strongly correlated with CMJ jump height (r = 0.74, p ≤ 0.01; r = 0.77, p ≤ 0.01), and FK peak force moderately correlated with CMJ peak velocity (r = 0.63, p ≤ 0.05). These findings suggest targeted arm strength training could enhance striking abilities, while improvements in leg acceleration strength may directly boost kicking performance and vertical jump capabilities, which are crucial in combat scenarios.

Although a growing number of evidence emphasizes superior of VATS over conventional thoracotomy, still is little known about early postoperative diaphragm muscle function after lobectomy via these two approahces. To fill the gap in existing literature, we conducted comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, magnitude of effort and potential risk of dysfunction such as: atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled into this study. The control group was consisted of 28 health subjects without medical condition could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function - compared to baseline data. Postoperative reduction of diaphragm contraction was demonstrated in all of 59 patients. In case of control group, the differences between measurements were no observed. We noted that lobectomy via thoracotomy was linked with greater percentage of patients with diaphragm paralysis or/and atrophy that VATS. Similar findings were observed in refer to diaphragm magnitude effort, as well as, diaphragm contraction strength, where minimal invasive surgery was associated with better diaphragm function parameters - in comparison to thoracotomy. Disturbance of diaphragm work was reported both at operated and non-operated side. Upper right and left lobectomy was connected with greater diaphragm function impairment than other segments. In conclusion, VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of a main respiratory muscle.

The future index prices are viewed as a critical issue for any trader and investor. For this craving, various models have shown up in the literature. The Geometric Brownian motion (GBM) is one of the popular models. This work examines four types of GBM as per the presence of memory or kind of volatility. These models include classical GBM with memoryless and constant volatility assumptions, SVGBM with memoryless and stochastic volatility assumption, GFBM with memory and constant volatility assumption, and SVGFBM with memory and stochastic volatility assumption. These models are utilized in an empirical study to forecast the future index price of Energy Sector in the Saudi Stock Exchange Market. The assessment was led by utilizing two error standards, mean square error (MSE) and mean absolute percentage error (MAPE). The outcomes showed that the SVGFBM occupies the highest level of accuracy according to smallest values of MSE and MAPE. While the accuracy of GBM come in the tail of the list models under study. These results have affirmed the positive affection of combining memory and stochastic volatility assumption into the GBM model, which agreed findings of numerous earlier works. Furthermore, the findings showed the GFBM models are more accurate than GBM models regardless of the type of volatility. While, under the same type of memory, the models with stochastic volatility assumption are more accurate than the corresponding models of constant volatility assumption. In general, all models considered in this work uncovered high accuracy through the value of MAPE ≤ 10%. This indicates of the ability of applying these models in a real financial environment. Through this empirical study, we can say that the Energy Sector in Saudi Arabia is predictable and stable and afterward we urge financial investors and stockholder to trade and invest in this sector.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Livestock farming plays a crucial role in agriculture and is important in meeting people's needs for a better life in the new era. However, due to China's "double carbon" target, the development of animal husbandry has been affected by the level of carbon emissions. To study the spatial dis-tribution and dynamic evolution of livestock carbon emissions in Shandong Province, we used panel data from 16 prefecture-level cities in Shandong Province from 2001 to 2022 to determine the spatial differentiation of livestock carbon emissions in Shandong Province and their dynamic evolution by combining spatial and non-parametric estimation methods based on livestock carbon emissions and livestock emission intensity measured by city. The results of the study show that the distribution of carbon emissions from animal husbandry in Shandong Province is in a "dis-persed-aggregated" pattern, and the intensity of carbon emissions shows a gradual downward trend, with a ladder-like distribution characterized by high in the west and low in the east. Through the analysis of the dynamic evolution of nuclear density, we observe that the regional differences of animal husbandry carbon emissions in Shandong Province are expanding, showing the characteristics of polarization. The difference of carbon emissions in the peninsula is gradually narrowing, and the phenomenon of polarization is weakening. The carbon emissions of animal husbandry in the central and western regions of Shandong are polarized.

In Germany, the phloem sucking planthopper Pentastiridius leporinus (Hemiptera: Cixiidae) currently represents the epidemiological driver for the spread of the syndrome “Basses Richesses” in sugar beet, which results in a reduced sugar content and an economic loss for the farmers. This disease is associated with the γ-proteobacterium ‘Candidatus Arsenophonus phytopathogenicus’ and the Stolbur phytoplasma ‘Candidatus Phytoplasma solani’. Recently, P. leporinus was found in potato fields in Germany associated with Stolbur-like symptoms in this crop. In this study, we confirmed that the vector completes its lifecycle on sugar beet as well as on potato when reared under controlled conditions. Transmission experiments with adults of this vector combined with molecular analyses showed for the first time that both pathogens are transmitted by this vector to potato. For an accurate assessment of the Ca. P. solani and Ca. A. phytopathogenicus titers in the vector and host plants, gBlocks derived from the hsp20- and 16S rRNA gene were employed, respectively. For Ca. P. solani the limit of detection was determined in potato and sugar beet material. The results of this study will further research on the epidemiology of the syndrome “Basses Richesses” and “Stolbur” diseases and the response of host plants and vector insects to both pathogens.

Fingerprints are essential for human identification and are valuable tools in criminal investigations. The pursuit of new materials for digital printing is expanding, with increasing interest in natural compounds such as bixin, sourced from annatto seeds. Despite its traditional use as a natural dye with medicinal properties, the potential of bixin in papilloscopy remains largely untapped. In this study, we meticulously extracted bixin from annatto seeds and meticulously developed composites incorporating zinc carbonate (bixin/ZnCO3) and kaolinite (bixin/kaolinite). UV-visible spectroscopy was used for characterization, and the extracted bixin showed absorption peaks at 429, 453, and 481 nm, which were very similar to standard peaks at 429, 457, and 487 nm. The two samples also had the same retention times (7.07 min) according to further liquid chromatography analysis. Sweat pores were easier to detect thanks to the effectiveness of the bixin/ZnCO3 and bixin/kaolinite composites in creating high contrast sebaceous and natural latent fingerprints. These results highlight the composites’ potential as novel and fascinating instruments for papilloscopy applications, which might also improve forensic investigations.

Hund's rule of maximum multiplicity is a powerful empirical tool for determining the electron population of electronic shells. It was recently discovered that it is also the rule of minimum Shannon entropy. This study extends these findings to the Aufbau rule and discusses them from the perspective of emergent dimensionality, providing a monotonically increasing entropy function. We observed that some elements that violate the Aufbau rule have the same entropies in the actual and Aufbau electron configurations. On the other hand, lower entropies of all actual elements' configurations are associated with higher or equal numbers of unpaired electrons in these configurations compared to the Aufbau configurations. The only exception to this rule is palladium.

Background. Azithromycin (AZM) is widely used in cystic fibrosis (CF) treatment following clinical trials demonstrating improved lung function and fewer pulmonary exacerbations. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF macrophages. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. Methods: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs) were differentiated into monocyte-derived macrophages (MDMs) and infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. Results: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected, however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM did not restore endocytosis in CF, another essential feature of M2 macrophages. Conclusions: This study highlights the cellular functions and molecular targets of AZM which may involve improved uptake of both gram-positive and gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

Latin America and the Caribbean offer the most favorable natural and social conditions for the emergence of cattle ranching that regenerate and maintains the ecosystem services on which life on Earth depends, that is energy efficient and that contributes to meeting fundamental human food needs. Unlike other major global producers, cattle farming in Latin America and the Caribbean is fundamentally based on pasture. Therein lies both its strength (due to the regenerative potential of well-managed pastures) and its vulnerability (due to the pervasive link between deforestation and pasture formation, especially in the Amazon, where 40% of the Brazilian herd is concentrated). The diversification of pastures (today marked by impressive monotony, with brachiaria accounting for 85% of the species in Brazil), the introduction of legumes and tree plantations within them, and the proper management of herds, open the way to the possibility of drastically reducing the area currently occupied by the activity (especially in the Amazon) while maintaining the supply of its products. Agricultural research has disseminated forms of moderate intensification of cattle ranching, which represent a low opportunity cost of animal feed and, at the same time, regeneration of ecosystem services that have so far been destroyed by the prevailing methods of farming.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.