In this article we report the first investigation over time of the atmospheric conditions around TGFs occurrence, using GPS sensors in combination with geostationary satellite observations and ERA5 reanalyses data. The goal is to understand which characteristics are favourable to the development of these events and to investigate if any precursor signals can be expected. A total of 9 TGFs, occurred at a distance lower than 45 km from a GPS sensor, were analysed and two of them are shown here as an example analysis. Moreover, the lightning activity, collected by the World Wide Lightning Location Network (WWLLN) was used in order to identify any links and correlations with TGF occurrence and PWV trends. The combined use of GPS and the stroke rate trends identified, for all cases, a recurred pattern in which an increase of PWV is observed on a timescale of about two hours before the TGF occurrence that can be placed within the lightning peak. The temporal relation between the PWV trend and TGF occurrence is strictly related to the position of GPS sensors in relation to TGF coordinates. The life cycle of these storms observed by geostationary sensors, described TGFs producing clouds as intense with a wide range of extensions and, in all cases, the TGF is located at the edge of the convective cell. Furthermore, the satellite data give an added value in associating the GPS water vapor trend to the convective cell generating the TGF. The investigation with ERA5 reanalyses data showed that TGFs mainly occur in convective environment with not exceptional values with respect to the monthly average value of parameters measured in the same location. Moreover the analysis showed the strong potential of the use of GPS data for the troposphere characterization in areas with complex territorial morphology. This study provided indications on the dynamics of convective systems linked to TGFs and will certainly help refine our understanding on their production highlights a potential approach through the use of GPS data to explore the lightning activity trend and the TGFs occurrence.

In this paper, we used meteorological data to simulate vertical profiles of optical turbulence at the Special Astrophysical Observatory (Russia, 43°40′19 ′′ N 41°26′23′′E, 2100 m a.s.l.), site of the 6-m Big Telescope Alt-azimuthal. The vertical profiles of optical turbulence are calculated using ERA-5 reanalysis data. These profiles are corrected using DIMM measurements as well as estimations of atmospheric boundary layer heights. We may note that the method basically reconstructs the most important features of the shape of the measured profile under clear sky. Atmospheric turbulent layers were identified, and the strength of optical turbulence in these layers was estimated. The model hourly values of seeing corresponding to the obtained vertical profiles range from 0.85 to 2.10 arcsec, values of the isoplanatic angle vary in the range from 1 to 3.0 arcsec (at λ = 500 nm). These estimations are close to the measured median of seeing (1.21 arcsec).

Ever since the virus was discovered in the 80s of the 19th century, plant viruses had a great impression within the field of plant pathology. In this book we trace the growth in the research on plant viruses beginning from traditional era (1882-1900) in which a new pathogen was discovered other than fungi and bacteria, later known as virus; biological era (1900-2000) in which the mode of spread and relationship of the virus with its vector was understood; biochemical/biophysical era (1930-1968) that marked the basis of virus purification and chemical characterization; molecular era of plant virology (1943-1995) in which establishment, progression & transmission of plant viruses was described within the host at molecular details ; era of viral molecular genetics (1980–2000), in which a significant role was played by the plant virologists to understand the position and function of genes, methods of viral gene cloning, gene silencing and other viral genome associated properties ; era of plant viral diagnostics (1980 – 2021) which led to rapid, specific and sensitive detection of plant viruses.

ABSTRACT Education is the most important instrument in human life because education can increase human dignity. In addition, education can also be a benchmark for human quality and an example of the progress of a nation. The history of education in Indonesia has evolved from the colonial era to the digital era. These developments have influenced government policies in every era. In the 21st century, the development of education in Indonesia is starting to show progress. This is because it is supported by the rapid growth of information and technology. This research article aims to analyze the educational policies carried out by the government from the colonial era to the digital era to be used as evaluation material at this time so that in the future education in Indonesia is even better. To achieve this goal, this research focuses on the question of how is the transformation of education in Indonesia from the colonial era to the digital era? and what is the paradigm of education in Indonesia when viewed from a historical perspective?. The research method used is the Literature Review method from 27 sources in journal articles, websites, and data reports for 2019-2021. The results of this study found that changes in the Indonesian education system from time to time have a positive influence on the progress of the Indonesian nation. The development of education in Indonesia also has an impact on increasing the Human Development Index (HDI). This shows that the quality of Indonesian society is increasing. Based on the results obtained, it is hoped that it can provide information about the transformation of education in Indonesia from the colonial era to the digital era from a historical perspective. This article is suitable as a reference source for education observers in Indonesia to know the history of education and its policies from the colonial era to the digital era and useful for academics to know the history of education in Indonesia. This research has limitations, namely this research is only limited to the development of education in Indonesia from the colonial era to the digital era and the paradigm of education development in Indonesia from a historical perspective.

Earnings management and financial distress are two critical facets of financial management in corporations that have lately been the focus of thorough research from both scholars and practitioners. The purpose of the research is to evaluate the influence of financial distress on the earnings management of companies listed at the NSE during the pre- and post-COVID eras. Multiple linear regression was applied in this study to examine the causal association between earnings management and financial distress. To assess the effect of financial distress on earnings management, the study analyzed data from 37 listed companies during the pre-COVID and post-COVID periods. The methodology also takes into account control factors like firm size, GDP, and inflation. The pre-COVID research indicates a significant positive correlation between financial strain and earnings management. In contrast, the correlation between financial distress and earnings management is not statistically significant in the post-COVID analysis. However, research shows that firm size has a statistically significant negative influence on managing earnings. The results of this study show that smaller firms are more inclined to engage in earnings management during the post-COVID era than bigger ones.

Introduction: Industrial revolution 4.0 in the current era of globalization plays an active role in the modern era in Indonesia. The influence of increasingly advanced technology affects the millennial generation as the nation's next generation to make Pancasila the basis of the State or the foundation of a State. In addition, the millennial generation has begun to shift the guidelines of life from Pancasila so that the appreciation of Pancasila values is starting to disappear along with the development of the times and in line with the progress of Science and Technology (IPTEK). If this continues, then the values of Pancasila will be replaced by a new ideology that will cause behavioural changes in society. Purpose: this study aims to provide the proper application to millennial life using Pancasila values, knowing the behaviour of the millennial generation towards the implementation of Pancasila values, and making Pancasila a way of life. Methods: the method used in this research is Literature Review and takes sources from journals published in 2019 to 2021 related to the Pancasila theme and the millennial generation. Results: the study results show that with the existence of Pancasila as the ideology and principle of the State, it is expected to strengthen the attitude and nature of the community in accepting things outside the norms that exist in Indonesia. In addition, the younger generation is expected to be able to apply Pancasila values along with the development of science and technology in the modern era and current globalization. The research question is how to make the millennial generation implement Pancasila in life in the contemporary period and what solutions can continue to instil Pancasila values ​​in the 4.0 industrial revolution. Recommendation: the conclusion drawn is that Pancasila can become a unifying tool for the nation if the current generation or millennial generation still desires to maintain its values ​​, even though they are in a modern era and many influences from its outside cultures. Limitation: the limitation of this research is not getting all the data directly from the source. The researcher recommends using primary data for the following study to ensure its truth and accuracy better because the researcher directly obtains it.

Abstract: The overuse of antibiotic prophylaxis during the COVID-19 pandemic would have led to the devel-opment of antibiotic-resistant bacterial strains, thereby increasing the epidemiological burden of antimicrobi-al resistance. The aim of this study was to determine the prevalence and antibiotic resistance pattern of bacte-ria isolated in 02 referral health facilities in Yaoundé before and during the COVID-19 pandemic era. We conducted a retrospective study over a period of 03 years (from 1 January 2019 to 31 December 2021) in the bacteriology units of the Central and General Hospitals of Yaoundé, Cameroon. The review of the services' registers was done to record bacterial isolates (Streptococcus, Staphylococcus, Neisseria meningitidis and Entero-bacteriaceae) as well as their susceptibility to selected, specific and highly potent antibiotics: Cefixime, Azythromycin and Erythromycin. The relationship between each group of resistant bacteria and the antibiotic of interest was determined by simple linear regression; the comparison of the prevalences of before (2019) and during 2 consecutive years of the COVID-19 pandemic onset (2020 and 2021) was done by the Chi2 test of in-dependence. In all, 426 bacterial strains were included. It appeared that the highest number of bacteria iso-lates and lowest rate of bacterial resistance were recorded during the pre-COVID 2019 period in 2019 (160 isolates vs. 58.8% resistance rate). Conversely, lower bacteria stains but greater resistance burden were rec-orded during the pandemic era (2020 and 2021) with the lowest bacteria amount and peak of bacteria re-sistance registered in 2020, the year of COVID-19 onset (120 isolates vs. 70% resistance in 2020 and 146 iso-lates vs.58.9% resistance in 2021). In contrast to almost all others groups of bacteria where the resistance burden was quite constant over years, the Enterobacteriaceae exhibited greater resistance rate during the pandemic period [60%(48/80) in 2019 to 86.9%(60/69) in 2020 and 64.5%(61/95) in 2021)]. Concerning antibiotics, unlike Erythromycin, Azythromycin related resitance increased during the pandemic period and the resistance to Cefixim tends to decrease the year of the pandemic onset (2020) and re-increase one year therafter. A significant association was found between resistant Enterobacteriaceae strains and Cefixime (R= 0.7; P-value= 0.0001) and also, between resistant Staphylococcus strains and Erythromycin (R= 0.8; P-value= 0.0001). It could be that the more frequent use of these antibiotics has increased resistance rate especially in Enterobacteriaceae. Anticromicrobial resistance should be closely monitor during and after COVID pandemic era.

Character education is essential for the current millennial generation and must be applied in everyday life in the surrounding community. The character of the millennial generation is different from the previous generation, which requires us to pay more attention to character education which is starting to erode along with the times. The Millennial generation is a generation that in everyday life can never be separated from science and technology. In this digital era, the millennial generation has a social function of strength in technology. In this study, there are research questions that will be discussed in this article, namely the first regarding what problems occur in the millennial generation who occupy the digital era?. Second, what is the important role and influence of the digital era on character education for the millennial generation in Indonesia?. Writing this article uses a qualitative research method, namely a literature review study, where researchers use or look for references from journals or books. Samples of respondents were taken randomly from each region, and there were ten respondents. From this research, it is found that the millennial generation in the digital era chooses to use social media to access the latest news and information rather than reading print media that contains education. This article aims to find out the importance of character education for the millennial generation, which is starting to erode with the times in the digital era. Many people underestimate character education, especially for the current millennial generation. Therefore, we must implement educational programs at any level, especially in Indonesia, because the character shows the national identity. This article will discuss the vital role and influence of character education for millennials who live in the digital era to be aware of the importance of character education in citizenship.

From professors overwhelmed by anxiety-driven e-mails from students, through faculty and administrative staff wasting valued time on e-mail minutia, misuse of electronic mail in the academy has become ubiquitous. After a brief overview of the unique features of e-mail communication, this study provides insight and guidelines to plan new educational activities on healthy and productive utilization of e-mail in the academy of the digital era. The overall aim is to prioritize scholarly deep work by focusing on teaching and research work, freeing working time wasted on unproductive use of e-mail.

A general method is presented that permits enantiomers, originally present in a low enantiomeric excess (%ee1), to accumulate in a high %ee (%ee2) without a chiral source present. An equation was derived that demonstrates the final %ee2 of any unreacted chiral starting material will become higher when that starting material has reacted to generate an additional chiral center, hence forming two sets of diastereomeric enantiomeric products. Importantly, chiral amplification factor (multiples), %ee2/%ee1, depends on the yield of this reaction (p), which exhibits a nonlinear increase in amplification as p approaches 100%. This process is inevitable. It represents a possible route by which small initial %ee1 values of prebiotic molecules could have been raised to high %ee2 contents during the pre-evolution of life period on Earth, without the need for an added chiral source to be present. This predicted behavior was then experimentally verified in Pictet-Spengler reactions of L-tryptophane methyl ester (L-TME) samples present in low enantiomeric excess (%ee1) with biacetyl or oxaldehyde (model reactions) run to various yields. Each reaction generates stereoisomer products, and chiral amplification of the L-TME’s initial %ee1 values to higher %ee2 values occurs in the unreacted (recovered) L-TME. Repeated cycles of these reactions create very high L-TME %ee values. Self-cyclodimerization of low %ee1 L-amino acids with their D-enantiomers to generate L,L-, D,D- and L,D-cyclic products were computationally studied, leading to the same conclusion. Small %ee1 values are enhanced to larger %ee2 in the unreacted starting materials.

Background: Currently, Indonesia is entering an era that is all digital and uses technology in all fields of activity. The internet has a lot to do with their behavior or character. Millennials are the nation's next generation. The emergence of the digital era caused by globalization has made the millennial generation less appreciative and practicing the values ​​of Pancasila. In this case, character education is something that must be applied to the millennial generation. Purpose: This study aims to analyze the characteristics of the millennial generation, the role of character education in realizing the values ​​of Pancasila in the daily life of the millennial generation, how to cultivate an attitude of patriotism and nationalism towards the nation by practicing Pancasila, and provide motivation for the millennial generation to realize these values. Pancasila values. Methods: This study uses a literature review method. The search for journals was carried out using the google scholar database with the keywords “Character Education”, “millenial generation”, and “Pancasila”. The journals selected are journals from 2019 to 2020. Results: By applying character education to the millennial generation, it will make it easier for them to practice the values ​​of Pancasila. Pancasila should be the way of life of the millennial generation. Recommendation and limitation: As millennials, we must protect the country from values ​​that are contrary to Pancasila. Character education must be applied following the nature of the millennial generation itself. Of course, the applied character education must prioritize and be based on the values ​​of Pancasila as well.

Background: The outbreak of the Covid-19 pandemic has significantly affected the operations of higher education institutions. Due to the limited use of video conferencing and cloud computing in these facilities, distance learning became the only option available to them. Objective: The study focused on identifying the most common types of attacks that can affect e-learning assets. Results: There was a lack of clear cybersecurity policies for educational institutes and universities in 2020, according to a report by Microsoft Security Intelligence. The report showed that the education industry was the most targeted sector for malware attacks in the last 30 days. Conclusion: The recommendations for improving the security of e-learning systems. Some of these include implementing policies that restrict access to the resources and applications, updating security patches, and using cryptographic protocols.

Background: Online teaching has resulted in university students adopting a sedentary lifestyle. Prolonged sitting and reduced physical activity due to pandemic restrictions have led to musculoskeletal pain in various body areas, significantly impacting the students’ quality of life. This study aims to investigate the effects of remote learning on Sicilian physiotherapy students during the COVID-19 pandemic, specifically focusing on the occurrence of musculoskeletal pain. Methods: An observational study was conducted using an online survey administered through Google Forms. The survey consisted of 26 multiple-choice questions and was distributed to students enrolled in Physiotherapy programs at the Universities of Catania, Messina, and Palermo. Participants were contacted via social channels or email, and data collection spanned 5 weeks. The collected data were analyzed using R software. Results: A total of 128 questionnaires were collected. More than half of the students (51.6%) reported dedicating 15–22 h per week to distance learning for a duration of 6–12 months (50%). Regarding study location, most students preferred studying at a desk (82.8%), with slightly over half (57.8%) adopting a backrest while studying remotely. Analysis of the students’ posture during study hours revealed common positions, including tilting the head forward by more than 20 degrees (47.8%), leaning the trunk forward by more than 20 degrees (71.9%), both shoulders being hunched forward (57.0%), wrists positioned above the level of the elbows (46.1%), thighs pointing upwards (41.4%), and one or both feet in a downward or dorsiflexed position (69.5%). Conclusion: The questionnaire responses indicate that the lifestyle of university students, influenced by online teaching, has deteriorated, leading to musculoskeletal pain, including myofascial pain. These results are primarily influenced by the adopted posture and the duration of time spent in these positions.

Opera and oratorio overtures exist in an indeterminate state between purely symphonic and dramatic music. While they can be and often are extracted for symphonic programs, they are ultimately tied to the story to which they grant the audience a preview of the story and music yet to come. Those that are easily extracted are so independent due to their structure, one well known to the symphony: the sonata form. In studying overtures from the 19^th century, however, one can trace a decline of the sonata form overture for one that is more subservient to the dramatic story soon to follow it. In this paper, three representatives of the early, mid and late period of the highlight this steady shift away from sonata form. Using Hepokoski and Darcy’s Elements of Sonata Theory: Norms, Types, and Deformations in the Late-Eighteenth-Century Sonata, I will categorize these overtures into one of the five sonata types listed therein. The increasing number of deformations as one moves through the overtures chronologically will illustrate the deliberate decline of use of the sonata form for the overture in favor of a clearer reflection of the upcoming story.

Some herbicides exert hormetic or biphasic non-monotonic dose-response (NMDR), which is one of the major challenges for ecological risk assessment (ERA) of pesticides pollution. In this study, fish embryo toxicity test (FET) with Javanese medaka (Oryzias javanicus) to sublethal concentration of diuron was determined. Inverted U-shape heart rate was observed at 3 days post-exposure (dpe) and 7 dpe. However, at 13 dpe the heart rate (104 ± 2.90 heartbeat/min.) decreased in 10.00 mg.L-1 exposed-embryos. At 20 dpe, hatchability and survival rate were reduced in 5.00 mg.L-1 and 10.00 mg.L-1 exposed groups. Hormetic developmental deformities were observed in embryo-larvae of Javanese medaka. The results revealed a biphasic effect of low concentrations of diuron on some morphological and physiological features of Javanese medaka embryo-larvae, which might be attributed to endocrine disruption of this herbicide. Further studies to support these effects were recommended.

Bosentan, an endothelin-receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male apoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin and mice were randomized into 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 4) BO+ATG: Combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p<0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p<0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p<0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p<0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

This study delves into the dynamic intersection of artificial intelligence (AI) and English Language Teaching (ELT) within the post-pandemic educational landscape. Grounded in Constructivism, Connectivism, and Technological Pedagogical Content Knowledge (TPACK), this research explores how AI integration impacts language instruction efficiency, benefits and challenges perceived by St. Michael's College students, differences in learning outcomes, and its potential to address the digital divide. Employing a qualitative approach, the study employs a rigorous method that includes intensive in-depth reviews of literature, maximum purposeful sampling, informal interviews, observation, and thematic analysis. Through these methods, data was collected from 30 participants, leading to the identification of five key themes. Findings suggest that AI enhances instructional efficiency, offers personalized learning experiences, and bridges gaps in remote settings. However, challenges and the importance of pedagogical balance emerged. The study underscores the need for adaptive pedagogical strategies to fully harness AI's potential. Future directions and limitations are discussed, emphasizing the study's implications for shaping the future of ELT.

The measures related to climate change and international technology transfer have been closely intervened as most international environmental instruments, including the United Nations Framework Convention on Climate Change and Kyoto Protocol as well as Paris Agreement which contain the provisions concerning environmentally friendly technology transfer. However, technologies have not been transferred adequately owing to the flaws in the relevant provisions and due to the fact that most technologies are possessed by transnational corporations and other private sectors. In order to undertake the commitment by the governments of developed countries and at the same time, to conform the commercial activities of their respective private sectors to the level of promised international obligation, an uniform international technology transfer agreement needs to be established separately, particularly under the World Trade Organization regime in Post Pairs-Agreement era. This paper first explores the defects and challenges found in provisions related to technology transfer in existing environmental agreements, and examines the possibilities of concluding an international technology transfer agreement both from theoretical and practical perspectives. climate change;environmentally sound technology;international technology transfer;Post Paris-Agreement Era

Delve into the ebb and flow of human ingenuity as the researcher traces the evolution of writing from papyrus to pixels. Discover how humble instruments like quill pens and typewriters have propelled human into the digital frontier, forever reshaping the art of expression in the modern age. This article examines the evolution of writing tools from traditional pen and paper to digital writing in the modern age. It explores the development of writing materials such as papyrus, parchment, and paper, as well as the invention of writing tools including quill pens, fountain pens, and typewriters. The rise of digital writing tools, including word processing software and smartphones, is also discussed, along with their benefits such as increased efficiency and productivity, enhanced collaboration and sharing capabilities, and greater accessibility and flexibility. However, the article also highlights the challenges of writing in the digital age, including the impact of digital distractions on writing focus and quality, the issue of online plagiarism and copyright infringement, and the potential loss of traditional writing skills. The article concludes with recommendations for educators, school administrators, students, and researchers to strike a balance between digital and traditional writing practices, to embrace digital writing tools while preserving traditional writing skills, and to understand the importance of the evolution of writing. The theoretical frameworks of Social Construction of Technology (SCOT) Theory, Media Ecology Theory, and Activity Theory are also discussed in relation to the evolution of writing tools. Overall, this article provides valuable insights into the history, benefits, and challenges of writing in the digital age, as well as suggestions for navigating the future of writing and its tools.

The new need to move to an online mode of administration has necessitated the adoption of Software-as-a-Service (SaaS) and Platform-as-a-Service (PaaS). The conventional paper-based administrative memorandum is relatively costly, requires manpower, insecure and non-confidential, prone to unauthorized access and has a relatively slow cycle time; among others. An electronic memo (e-memo) can save cost, offer high speed of processing, reliability and security. The aim of this work was to conceptualize, design and develop a novel semantic web-based memo platform that allows for handling memos within an organization. The tools used include HTML, CSS, PHP, JavaScript, jQuery and AJAX, MySQL. The developed system was tested in three stages. Testing was done in the Department of Computer Science of the institution of case study, then in the Faculty of Science and finally in the entire Lagos State University. Agile development method was used in the development process. The designed system was hosted on a cloud-server and a total of 43 test cases were considered and an average of four minutes was recorded for a complete memo cycle. eMemo allows users to generate, sign, treat and memo electronically. It is such a useful tool that will enhance information processing in a faster, standardized and more secure manner.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

Pathophysiology of depression is related with reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well under-stood, but clinical studies have shown that administration of the fast-acting antidepressant keta-mine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction of depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus was observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin effect on stress, anxiety and structural changes in the limbic system and translate into antidepres-sant effect of psilocybin in depressed patients.

The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its selective conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently marketed drugs - the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat - that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.

DNA methylation is one of the epigenetic mechanisms which have been implicated in cellular differentiation, ageing and disease development. The effect of hypomethylating drug 5-aza-2´deoxycytidine (5-aza dC) on the biosynthetic profile of caudal region chondrocytes from chick sternum was studied in detail. The chondrocytes in culture were treated with varying doses of 5-aza dC for 48h and maintained subsequently without the treatment and harvested at selected time points for analysis of growth and differentiation status. 15µg/ml of 5-aza dC showed optimum Concentration at which there was a significant increase in DNA synthesis and RNA synthesis as per cell basis. There was also a significant increase in total protein synthesis and collagen synthesis as per cell basis at this concentration. This optimal concentration also showed to up regulate the gene expression of Type X collagen and alkaline phosphatase, which are the marker of hypertrophic chondrocyte expression. These results further support the notion that methylation is the major epigenetic factor controlling the differentiation and maturation of chondrocytes.

Abstract: Turmeric is a plant with multiple medicinal attributes. One of them being its analgesic effect. In this project the analgesic effect of the plant was evaluated with an inflammatory pain model: the 5% formalin model. Turmeric was administered to 250 g male Wistar rats (6 ± 2) provided by the Health Science department’s vivarium. The dose-response curve of the plant was per-formed observing the analgesic effect. Once the dose was selected, they were administrated within different turmeric protocols. 400 mg orally every 24 h for two weeks, another group with turmeric ad libitum for two weeks, the control group with 0.9% saline solution for two weeks, and a group with administration of metamizole prior to evaluation with 5% formalin. Subsequently, each rat was evaluated by 5% formalin intraplantarly and the number of rat paw twitches per 1 h was observed. The analysis of the data generated through the obtained results was carried out. The dose of 400 mg of oral turmeric was administered for two weeks without observing any collateral effects. An excellent analgesic effect was found in this protocol, as well as, in the ad libitum administration for two weeks compared to the control group. Likewise, turmeric presents a milder effect than metamizole, a well-known analgesic.

Nowadays, transactions carried out with digital currencies are increasing. Modern societies are asked to respond to growing challenges related to the management of digital currencies in their daily lives. However, due to the lack of digital skills of users, the management of digital currencies hides risks. To the best of our knowledge, the originality of the current research lies in the act of combining the concept of digital skills with the use of digital currencies. After all, the use of digital currencies is constantly increasing, which means that citizens should familiarize themselves with their use, an element that makes this study valuable for digital societies. Digital skills effectively contribute to the development of digital societies because they increase the employment of citizens, facilitate access to information, and contribute to the social inclusion of individuals through digital communication, while also increasing efficiency and productivity in the workplace. Also, the government and banking institutions can more effectively sensitize citizens to digital skills for more effective use of digital currencies. In this way, tax payments will be facilitated, the use of e-wallets will be safer, and e-governance will be greatly promoted, while the quality of banking services will be improved. The methodology of this study was based on the Digital Competence Framework for Modern Societies (DigComp) and was applied through a questionnaire completed by 443 respondents. The main objective was to evaluate their digital skills from the perspective of digital currency use. The analysis of the responses was carried out by using Structural Equation Modeling (SEM). The most important result from this research reveals that users of digital currencies are significantly capable of developing communication to solve everyday problems. At the same time, users of digital currencies mostly detect digital threats and effectively manage fake news without being affected by them. However, users of digital currencies consider that security issues are important, but only for transactions and not for their supporting functions. The study concludes with suggestions for improving the experience of digital currency users through individual actions, thus having a positive impact on the state and banking institutions.

The broad and rapid application of new genomic techniques (NGTs) such as CRISPR-Cas has led to a fast increase in the number of genetically modified crops. With the recently published EU Commission’s (EC) regulatory proposal on plants generated with NGTs (July 5, 2023) the process of admission of such genetically modified plants is aimed to get accelerated and simplified. NGT plant applications shall be categorized based on their molecular characteristics into category 1 NGT (NGT1) and category 2 NGT (NGT2), which is in divergence from the current legislation centered around Directive 2001/18/EC. In the regulatory proposal NGT2 plants are envisioned to undergo a reduced risk assessment while for NGT1 plants no risk assessment is foreseen at all. To demonstrate were the path of the proposal leads to in practice, we applied the proposed criteria for categorization to a list of NGT plant applications that are currently in the commercialization pipeline. A key finding is that out of those plant applications affected by the EC proposal, 94% would be classified as NGT1 and thus would receive a market approval without risk assessment, monitoring and sufficient labeling provisions. The remaining 6% of applications would be classified as NGT2 plants for which, in deviation from the current regulation, an adapted risk assessment is proposed. A screening of intended traits in the pipeline highlights that certain NGT1 plants can pose similar environmental risks (e.g. invasiveness) compared to other genetically modified organisms (GMOs), as defined in Directive 2001/18/EC. For example, NGT1 applications based on RNAi technology can exhibit insecticidal effects with potential side effects on non-target organisms (i.e. other insects). Our quantitative and case-specific elaboration on how the current EC regulatory proposal would affect the environment, health or consumer protection will be informative for decision makers and politicians.

In this inclusive review article, the focus is on navigating the dynamic landscape of literature education, particularly the profound pedagogical shifts observed in the aftermath of the pandemic. The article synthesizes global insights, delving into how educators have adapted to hybrid models and embraced digital tools, fundamentally transforming the reading, analysis, and engagement with literary works. Exploring the integration of digital tools in literature education, the review uncovers the transformative impact of technology on traditional pedagogies. It analyzes the challenges and opportunities inherent in adapting literature education to the digital era, emphasizing the need for inclusive practices and adaptability. The article concludes by suggesting future research directions, encompassing AI integration, inclusive practices, cultural variations, long-term effects of hybrid models, and effective pedagogical strategies for technology integration. With a comprehensive approach, this review not only summarizes the current state of literature education but also discusses its implications, offering a holistic understanding of the contemporary educational landscape and setting the stage for future research endeavors.

In an era of global connectivity, language and literature education faces the challenge of navigating multilingualism, cultural diversity, and technological advancements. This paper explores the challenges and opportunities in language and literature education in the era of global connectivity. Through a qualitative research approach, interviews, focus group discussions, and classroom observations were conducted with 30 Arts and Sciences students and teachers. The findings reveal significant themes related to cultural diversity, multilingualism, and the integration of technology in language learning. The study emphasizes the importance of inclusive pedagogies, critical thinking development, and the incorporation of authentic and diverse literary works. Recommendations are provided for educators and policymakers to promote intercultural understanding and enhance language and literature education. The limitations of the study suggest areas for future research, including long-term language proficiency and diverse contextual considerations. Overall, this paper calls for ongoing innovation and collaboration to meet the evolving needs of language and literature education in an interconnected world.

Abstract This qualitative research study was aimed at exploring Covid-19 pandemic and its impact via online engagement on disadvantaged undergraduate students resulting in digital divide. The study was supported by the connectivism theory. The methodology approach was an eight year (2014-2022) duration systematic literature review using Educational Resources Information Center (ERIC), Google Scholar, Scopus, and Web of Science (WoS) databases as advanced search strategies. Findings from the SLR provided 56 included relevant publications as confirmed in the Reference Section. Here, findings justified factors responsible for digital divide and the digital divide impacts. Connectivism was suggested as an approach to control digital divide. This study recommends connectivism to control digital divide experienced among disadvantaged undergraduate students in South African universities via numerous supports for free trainings in computer skills, while the government provides low data cost and free Wi-Fi services.

We have previously shown that 2-thiouridine (S2U), either as a single nucleoside or as an element of RNA chain, is effectively desulfurized under applied in vitro oxidative conditions. Chemically induced desulfuration of S2U resulted in two products: 4-pyrimidinone nucleoside (H2U) and uridine (U). Recently, we investigated whether desulfuration of S2U is a natural process that also occurs in cells exposed to oxidative stress or whether it only occurs in the test tube during chemical reaction with oxidants at high concentrations. Using different types of eukaryotic cells, such as baker's yeast, human cancer cells or modified HEK293 cells with impaired antioxidant system, we confirmed that 5-substituted 2-thiouridines are oxidatively desulfurized in the wobble position of the anticodon of some tRNAs. Quantitative LC-MS/MS-MRMhr analysis of nucleoside mixtures obtained from hydrolyzed tRNA revealed the presence of desulfuration products of mcm5S2U: mcm5H2U and mcm5U modifications. We also observed some amounts of immature cm5S2U, cm5H2U and cm5U products, which may indicate a disruption of an enzymatic modification pathway at the C5 position of 2-thiouridine. The observed process, which is triggered by oxidative stress in living cells, could impair the function of 2-thiouridine-containing tRNAs and alter the translation of genetic information.

Lysine succinylation, and its reversal by sirtuin-5 (SIRT5), is known to modulate mitochondrial fatty acid β-oxidation (FAO). We recently showed that feeding mice dodecanedioic acid, a 12-carbon dicarboxylic acid (DC12) that can be chain-shortened four rounds to succinyl-CoA, drives high-level protein hypersuccinylation in the peroxisome, particularly on peroxisomal FAO enzymes. But the ability of SIRT5 to reverse DC12-induced peroxisomal succinylation, or to regulate peroxisomal FAO in this context, remained unexplored. Here, we showed that feeding DC12 strongly recruits SIRT5 into hepatic peroxisomes. Knocking out SIRT5 impaired peroxisomal FAO as evidenced by reduced 14C-DC12 flux in liver homogenates and elevated levels of partially shortened DC12 catabolites in urine. Further, mass spectrometry revealed a trend toward less peroxisomal protein succinylation in SIRT5 knockout liver. This is consistent with reduced flux of DC12 through the peroxisomal FAO pathway, thereby reducing production of the succinyl-CoA that chemically reacts with lysine residues to produce protein succinylation. Mass spectrometry comparisons of site-level succinylation in wildtype and SIRT5 knockout liver did not reveal any clear pattern of SIRT5 target sites in the peroxisome after DC12 feeding. However, SIRT5 co-immunoprecipitated with 15 peroxisomal proteins including the key peroxisomal FAO enzymes acyl-CoA oxidase-1 and enoyl-CoA/3-hydroxyacyl-CoA dehydrogenase (EHHADH). In vitro, recombinant SIRT5 partially desuccinylated chemically modified recombinant ACOX1a, ACOX1b, and EHHADH. Desuccinylation by SIRT5 had no effect on enzyme activity for ACOX1a and EHHADH. For ACOX1b, SIRT5-mediated desuccinylation decreased activity by ~15%. Possible interpretations of this data are discussed.

The management of erectile dysfunction (ED) shows several grey zones, especially in terms of patient satisfaction and adherence to the treatment. The main and first-line treatment for ED is drug therapy, mainly phosphodiesterase-5 inhibitors (PDE-5is) but the adherence to the therapy is not optimal due to the low patient satisfaction reported in several cases. To address this issue, different administration routes and PDE-5is pharmacological formulations have been introduced in the pharmacological market. The pharmaceutical market has recently seen the introduction of a novel sildenafil oral suspension. This device offers access to all therapeutic regimens in one device, releasing 0.5 mL of suspension containing 12.5 mg of sildenafil with each pulse. This formulation enables tailored dosing based on clinical requirements and the demands of ED patients. Here, we aim to give a brief narrative review of the management of this new oral suspension in order to provide the readers with some suggestions to use in everyday clinical practice, on the basis of the recent evidence, by using an easy and rapid-to-consult questions and answers form. Also included are the conclusions of a board meeting of experienced andrologists regarding the most recent developments in this area.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

As mental health problems tend to increase during adolescence and is a serious public health issue in the Republic of Kazakhstan. Early detection is necessary and monitoring at the population level can be used to evaluate the progress of national programmes promoting positive well-being. Physical activity (PA) can be protective whereas increased screen time behaviours (STB) can be a risk for low levels of well-being. A national representative sample (n=4,731) of young adolescents aged 11y, 13y, and 15y from the Republic of Kazakhstan took part in the WHO collaborative Health Behaviour in School-aged Children (HBSC) study. Respondents completed the WHO-5 Well-being scale, and items in on PA and STB. Internationally recognised, recommended cut-offs were used for analyses. Two models of binary logistic regressions were performed to examine the associations with PA (Model 1) and PA with STB (Model 2) after stratification by gender and controlling for age, locality and family affluence. Three quarters of young adolescents in the Republic of Kazakhstan have good overall well-being, despite the proportion reduces as adolescents age from 11y to 15y (boys, OR=0.66 CI=0.49-0.80; girls, OR=0.55, CI=0.43-0.71). The odds ratio for positive well-being were more than twice for boys and more than 3.5 for girls who reported daily PA than not being active daily. Spending less time on STB for girls was associated with positive well-being than spending more STB time (OR=1.28, CI=1.04-1.59). Well-being among young adolescents drops dramatically between the ages of 11y and 15y and is higher among rural schools attendees than in urban schools. The recommended amounts of PA can be protective of low well-being for both boys and girls. However, meeting reporting STB recommendations was only protective for girls and not boys. Designing and implementing positive well-being programmes require consideration of locality and amounts of PA and STB

The string of bacteria, Vibrio. sp. QD-5 utilizing alginate, was separated from rotten kelp. The results of genome sequencing showed that the strain QD-5 contained four alginate lyase genes.One of the alginate genes Aly-IV was cloned and linked to the plasmid pET-22b (+). The heterologous expressed alginate lyase aly-IVwas characterized，which possessed the theoretical molecular mass of 62 kDa, and theoretical isoelectric point (pI) of 5.12. - The enzyme aly-IV was purified and the activity reached 1256.78 U/mg, with optimal temperature of 35 ^oC and pH value of 8.9. Nurtured in the temperature below 25 ^oC for 30 minutes, the activity was almost stable. The result also suggested that the activity of enzyme was strongly affected by - NaCl whose optimal concentration was 15 mM in a lab environment The TLC and ESI-TOF-MS analysis suggested that the enzyme aly-IV could degrade sodium alginate and polyG in endo-lytic type, producing monomer, dimer and trimmer. So, aly-IV can also be widely applied to make large scale preparation of alginate oligosaccharides with low degree of polymerization (DP).

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

The COVID-19 pandemic has invited us to envision education anew, embracing a new era of instructional practices and learning environments. This study explores language teachers' and students' experiences in the post-pandemic landscape, providing valuable insights into the challenges, adaptations, and opportunities. Grounded in socio-cultural perspectives and educational theories, such as Vygotsky's socio-cultural theory and Deci and Ryan's self-determination theory, the study employs Interpretative Phenomenological Analysis (IPA) to comprehensively analyze secondary data sources. Findings reveal the significant role of social interaction and cultural context in language learning, amid reduced face-to-face contact and increased reliance on technology. The study uncovers the intricate interplay between individual, interpersonal, and environmental factors, shedding light on educators' and learners' challenges. Autonomy, competence, and relatedness emerge as crucial for intrinsic motivation and optimal learning outcomes. While acknowledging limitations related to secondary data sources, the study offers a comprehensive overview of the literature, informing language education practices in the post-pandemic era. It contributes to understanding the complex dynamics and interactions within language education and calls for future research using primary data collection methods to explore experiences and perspectives further. By understanding post-pandemic experiences, this study aims to shape education policies, practices, and pedagogical approaches, supporting effective language learning and the well-being of educators and learners in this transformed educational context.

This paper presents the rationale for using ultra low intensity transcranial light photodynamic treatment (LIT-PDT) for treating glioblastoma. Glioblastoma is currently treated with maximal safe resection, temozolomide and ionizing irradiation. Mortality in 2024 remains at over 80% within several years from diagnosis. 5-aminolevulinic acid (5-ALA) is a heme precursor that is selectively taken up preferentially by malignant cells, including glioblastoma. Photon energy can be transduced to molecular oxygen by a 5-ALA metabolite, PpIX, transforming oxygen to the singlet state, a reactive oxygen species (ROS) that destroys or damages vital glioblastoma cell structures. In PDT, light energy ~ 100 to 200 J / cm2, at 630 nm is delivered intraoperatively after resection and preoperative oral 5-ALA. This generates ROS cytotoxicity in residual glioblastoma cells within the resection cavity wall. 630 nm light poorly penetrates skin, skull, and brain tissue. That currently restricts PDT to a single intraoperative session using high flux light. LIT-PDT addresses some current shortcomings of 5-ALA PDT treatment. Part 1 analyzes published data indicating that continuous ultra low light flux, 17 μW / cm2, over 24 hours for a total delivery of 1.5 J / cm2, is effective for 5-ALA PDT treatment. That opens the way for repetitive, extracranial light to deliver enough energy for low flux, long duration PDT to any deep brain structure using less than 12 W total distributed over the entire scalp area. In Part 2, by analysis of 5-ALA and PpIX physiology, it became apparent that four non oncology drugs - ciprofloxacin, deferiprone, telmisartan and ziprasidone, will increase energy capture by GB cells, thereby increasing PDT treatment cytotoxicity. A phased pilot study of LIT-PDT treatment is being planned.

Background: Glioma surgery was remarkably renewed in the past 2 decades, with improved safety and limited but yet improved life expectations. Fluorescence-guided resection of high-grade gliomas (HGG) plays a central role in this sense, by allowing higher degrees of extent of resection (EOR). The introduction of the exoscopic guided surgery may be considered an implementation for fluorescence techniques over the traditional microscopes. We present the application and the advantages of the exoscopic guided surgery compared to the microscopic surgery in tumor resection guided by 5-ALA fluorescence in patients with HGG. Methods: ten consecutive patients underwent a surgery for HGG resection. The surgery was performed via an exoscopic-guided procedure (Olympus Orbeye) and after oral administration of Gliolan 5 hours before the procedure. During surgery, the procedure was shifted to microscope (Kinevo 900, Zeiss) view. The intensity of the fluorescence under the two different was subjectively measured in different picture samples during the surgery in a 1 to 5 (from minimum to maximum) scale. The brightness of the surgical field and the detailing of the anatomy were also analyzed comparatively. Results: among the ten patients the histopathological diagnosis was an high grade glioma in all cases. In 9 cases was possible to achieve the gross total resection. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1–5, was 4.5 in the exoscope group and 3.5 in the microscope group (p<0.01). Conclusions: The exoscopic guided surgery adds advantages to the traditional fluorescence- guided surgery with 5-aminolevulinic acid. Beyond the important advantage of low cost and the possibility to perform collaborative surgeries, it adds a plain and continuous visualization of the tumor and the surgical field in the fluorescence guided glioma surgery compared to the microscopic guided one.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. In addition, tadalafil protected cerebral nerve development in FGR offspring. The clinical trials we have conducted to date, including a case–control study, a phase I trial, and a phase II trial, have indicated the efficacy of tadalafil in prolonging pregnancy, as well as a good safety profile for fetuses and neonates. The number of fetal, neonatal, and infant deaths was significantly lower in those receiving tadalafil treatment group than that in controls, and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

As one of toxic Volatile Organic Pollutant (TVOCs), formaldehyde has a toxic effect on microorganisms, and then inhibits the biochemical process of formaldehyde wastewater treatment. Therefore, the selective degradation of formaldehyde is of great significance to achieve formaldehyde wastewater high-efficiency and low-cost treatment. This study constructed a heterogeneous Fe-ZSM-5/H2O2 Fenton system for selective degradation to target compounds. By bonding Fe3+ onto the surface of ZSM-5 molecular sieve, Fe-ZSM-5 was prepared successfully. XRD, BET and FT-IR spectral studies shown the prepared Fe-ZSM-5 was mainly composed of micropores. The influences of different variables on formaldehyde selective heterogeneous Fenton degradation performance were studied. The 93.72% formaldehyde degradation and the 98.15% selectivity of formaldehyde compared with glucose had demonstrated in the optimized Fenton system after 360 min. Notably, the resultant selective Fenton oxidation system had a wide range of pH suitability from 3.0 to 10.0. Also, the Fe-ZSM-5 was used in 5 consecutive cycles, while the degradation efficiency of formaldehyde did not drop dramatically. Using reactive oxygen species scavengers, hydroxyl radical was the main active substance to degrade formaldehyde. Furthermore, the great degradation performance of this system to high concentration of formaldehyde was acquired, and the degrading efficiency was more than 95%.

Rice blast fungus (Magnaporthe oryzae) causes massive yield losses annually worldwide. The fungus secreted bunch of effector proteins target different rice cellular compartments to facilitate its infection. However, most of intensively studied effectors are small secreted proteins with high presence/absence polymorphism in the fungus, and effectors conserved among different species were rarely investigated. In this study, we identified MoPce1, a CAP/PR domain containing protein common in different species, as an important virulence factor from a screening of 145 putative core effectors (PCE). MoPCE1 is required for pathogenicity but not the asexual development. Ectopic expression of MoPCE1sp in ZH11 background compromised the plant resistance. We also found that MoPce1 lacks the conserved cysteine residuals in CAP domain, and is BIC-localized in invasive hyphae and nuclei-localized when ectopically expressed in tobacco leaves and rice protoplasts. These results suggested that MoPce1 may bind novel ligand(s) rather than sterol. Indeed, we found that MoPce1 could interact with OsDi19-5, a transcription factor in rice. We inferred from these results that MoPce1 is required for pathogenicity by suppressing the immune response in rice, likely through the interaction with OsDi19-5.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

Autophagy, an alternative cell death mechanism, is also termed programmed cell death type II. Autophagy in cancer treatment needs to be regulated. In our study, autophagy inhibition by desipramine or the autophagy inhibitor chloroquine (CQ) enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 [death receptor (DR5)] expression and subsequently TRAIL-induced apoptosis in TRAIL-resistant A549 lung cancer cells. Genetic inhibition of DR5 substantially reduced desipramine-enhanced TRAIL-mediated apoptosis, proving that DR5 was required to increase TRAIL sensitivity in TRAIL-resistant cancer cells. Desipramine treatment upregulated p62 expression and promoted conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, indicating that autophagy inhibition occurred at the final stages of autophagic flux. Transmission electron microscopy analysis showed the presence of condensed autophagosomes, which resulted from the late stages of autophagy inhibition by desipramine. TRAIL, in combination with desipramine or CQ, augmented the expression of apoptosis-related proteins cleaved caspase-8 and cleaved caspase-3. Our results contributed to the understanding of the mechanism underlying the synergistic anti-cancer effect of desipramine and TRAIL and presented a novel mechanism of DR5 upregulation. These findings demonstrated that autophagic flux inhibition by desipramine potentiated TRAIL-induced apoptosis, suggesting that appropriate regulation of autophagy is required for sensitizing TRAIL-resistant cancer cells to TRAIL-mediated apoptosis.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Viruses pose a great threat to people’s lives. Enterovirus A71 (EV-A71) infects children and infants all over the world with no FDA-approved treatment to date. Understanding the basic mechanisms of viral processes aids in selecting more efficient drug targets and designing more effective antivirals to thwart this virus. The 5´-untranslated region (5’-UTR) of the viral RNA genome is composed of a cloverleaf structure and an internal ribosome entry site (IRES). Cellular proteins that bind to the cloverleaf structure regulate viral replication, while those that bind to the IRES also known as IRES trans-acting factors (ITAFs) regulate viral translation. In this review, we survey the cellular proteins currently known to bind the 5’-UTR and influence viral translation and replication with emphasis on comparing proteins’ functions and localizations pre- and post-(EV-A71) infection. Comprehensive understanding of how the host cell’s machinery is hijacked and reprogrammed by the virus to facilitate its replication is crucial for developing effective antivirals.

The search for a continuous continental record of interglacial periods in semi-arid regions is problematic due to the absence of stable and continuous sedimentary systems over time in this type of climate. In this work, a relatively stable basin is described and analyzed during the last interglacial in a semi-arid region of the western Mediterranean. For this purpose a geomorphological, stratigraphic and sedimentological study has been carried out, with dating through 230Th. A semi-endorrheic Pleistocene basin has been identified, with two units that correspond to a fluvial-lacustrine system (unit P1) and an alluvial system (unit P2). Unit P1 has been dated in the MIS 5e interglacial episode. A framework is described in which the Aljezares Quaternary basin can be considered as a possible source of paleoenvironmental and paleoclimatic information in semi-arid regions from the last interglacial period in future studies.

Reduced glutathione (GSH) is an antioxidant in plants and is one of the important ways for plants to combat low-temperature stress. In this paper, Eriobotrya japonica Lindl. cv. Zaozhong No. 6 seedlings were used to study the effects of exogenous 5-aminolevulinic acid (ALA) application on glutathione synthesis and cyclic metabolism of loquat seedlings under low-temperature stress and to explore the regulatory mechanism of ALA on loquat cold tolerance. The results showed that ALA treatment could increase the content of GSH and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in loquat leaf slices under low-temperature stress; reduce the electrolyte leakage rate and GSSG, H₂O₂ and MDA contents in leaf tissues; and alleviate the peroxidation damage caused by low temperature. ALA treatment increased the activity of γ-glutamine synthetase (γ-ECS) in loquat leaf slices under low-temperature stress and promoted the biosynthesis of reduced glutathione, thereby increasing the GSH content in leaf tissues. On the other hand, ALA treatment could also improve the activities of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and promote the cyclic regeneration of GSH, accordingly maintaining a high GSH/GSSG ratio, promoting the removal of reactive oxygen species (ROS), and enhancing the antioxidant capacity of leaves. The regulatory effect of ALA on enhancing the antioxidant capacity of loquat seedlings under low-temperature stress can be inhibited by L-buthionine-sulfoximine (BSO, GSH biosynthesis inhibitor). The results showed that ALA improved the antioxidant capacity of loquat seedlings under low-temperature stress, and GSH was involved in the regulation of the antioxidant effect of ALA on loquat seedlings under low-temperature stress.

Trace amine-associated receptor 5 (TAAR5) is a G protein-coupled receptor that belongs to the TAARs family (TAAR1-TAAR9). TAAR5 is expressed in the olfactory epithelium and is responsible for sensing 3-methylamine (TMA). However, recent studies showed that TAAR5 is also expressed in the limbic brain regions and is involved in the regulation of emotional behaviour and adult neurogenesis, suggesting that TAAR5 antagonism may represent a novel therapeutic strategy for anxiety and depression. We used the AtomNet® model, the first deep learning neural network for structure-based drug discovery, to identify putative TAAR5 ligands and tested them in an in vitro BRET assay. We found two mTAAR5 antagonists with low to submicromolar activity that are able to inhibit the cAMP production induced by TMA. Moreover, these two compounds also inhibited the mTAAR5 downstream signalling, such as the phosphorylation of CREB and ERK. These two hits exhibit drug-like properties and could be used to develop further more potent TAAR5 ligands with putative anxiolytic and antidepressant activity.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the road for the emerging nanomedicine as a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 was reported in lung, colon, metastatic breast cancers and bladder squamous carcinoma. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. Sildenafil had been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the expression of Bad and Bax proapoptotic proteins. It was also reported that the use of sildenafil prior to the administration of Doxorubicin (DOX) increased its EPR-related concentration in breast cancer tissues by 2 folds. Further, a substantial reason of anticancer chemotherapeutic failure is due to multidrug resistance (MDR), exacerbated by the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCCs. Sildenafil has demonstrated inhibitory effects on the efflux activity of ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing MDR caused by these transporters. In this review, we critically examine the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery pointing up the outcome of the most important related preclinical and clinical studies.

Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136–4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.

The three heat-induced coffee contaminants acrylamide, furfuryl alcohol (FA) and 5-hydroxymethylfurfural (HMF) were analyzed in a collective of commercial samples as well as in Coffea arabica seeds roasted under controlled conditions from very light Scandinavian style to very dark Neapolitan style profiles. Regarding acrylamide, average contents in commercial samples were lower than in a previous study in 2002 (196 compared to 303 µg/kg). The roasting experiment confirmed the inverse relationship between roasting degree and acrylamide content, i.e. the lighter the coffee the higher the acrylamide content. However, FA and HMF were inversely related to acrylamide and found in higher contents in darker roasts. Therefore, mitigation measures must consider all contaminants and not be focused isolatedly on acrylamide, specifically since FA and HMF are contained in much higher contents with lower margins of exposure compared to acrylamide.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells by pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as nutrient, PNPOx participates only in the salvage pathway. Transferring PLP produced by PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting to specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx enzymes from different organisms maintain PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding influencing substrate transformation at the active site. Despite shared features, species-specific regulations are evident among PNPOx enzymes.

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

Abstract: Malnutrition in children aged 0-5 years is a significant public health concern in many societies and is influenced by various sociodemographic factors that, when understood, may improve intervention planning and results. Background. This study aimed to identify the sociodemographic determinants of malnutrition in rural and urban areas of Abia State, Nigeria. Methods. A cross-sectional observational study involving 842 children (aged 6-59 months) and their caregivers was conducted across selected rural and urban areas in Abia State, Nigeria. Data collected through semistructured questionnaires focused on sociodemographic information as well as anthropometric measurements such as weight, height, and mid-upper arm circumference (MUAC). The dietary diversity score (DDS) was also calculated for each child via a questionnaire that recorded the consumption of various food groups over a 7-day period. Chi-square tests were adopted for categorical variables, whereas binomial logistic regression was used to identify determinants of malnutrition and weight classification. Results. Marked sociodemographic differences were found between rural and urban caregivers, with urban caregivers being more likely to have higher knowledge of nutrition (p < 0.01) and education (p < 0.01). Malnutrition, indicated by global acute malnutrition (GAM), was significantly higher in rural areas (53.5%) than in urban areas (46.5%) (χ2 = 5.353, p = 0.021). Logistic regression revealed that children of caregivers in rural areas were more likely to have an abnormal BMI-for-age (AOR: 1.407, 95% CI: 1.001–1.978, p = 0.049), whereas children of caregivers in urban areas were less likely to be malnourished (COR: 0.565, 95% CI: 0.347–0.921, p = 0.022). Conclusion. Implementation scientists should focus on enhancing caregiver education, particularly in rural areas, to promote awareness of diets, thereby reducing malnutrition.

Cholangiocarcinoma is an aggressive cancer with limited treatment options. Current therapies, such as cisplatin and 5-fluorouracil (5-FU), often cause side effects and drug resistance. This study investigated a potential new approach by combining a peanut skin extract (KK4-PSE) with these drugs. The extract effectively inhibited the growth of cholangiocarcinoma cells in laboratory studies and showed even greater selectivity for cancer cells compared to healthy cells. When combined with cisplatin or 5-FU, KK4-PSE enhanced the drugs' effects, leading to cell cycle arrest and increased cell death. These combined treatments also reduced levels of proteins that promote cancer cell survival. In animal models, KK4-PSE combined with 5-FU showed superior tumor suppression compared to the combination with cisplatin. Overall, these findings suggest that KK4-PSE may be a promising synergistic agent to improve the effectiveness of chemotherapy for cholangiocarcinoma, warranting further clinical investigation.

This survey of research literature is an overview of the current state of science addressing DSM-5 diagnostic criteria as it relates to identifying Autism Spectrum Disorder (ASD) in young children. Selected sources are of high quality and have been published since 2020 in peer-reviewed journals relevant to children’s health. The narrative is organized from the earliest to the most recent publications and is divided into sections around categories and themes that highlight the main arguments, findings, and controversies identified by researchers. There are indications in the literature that while ASD can be identified and differentiated from other developmental disorders in young children, doing so requires that clinicians who have relied on the DSM-5 should also use multiple measures, including other formalized screening tools as assessments that gather observational input from parents and caregivers, as well as findings from physical examinations, laboratory investigations, and magnetic resonance imagining (MRI). This high level of corroboration points to an emerging diagnosis paradigm through which transdiagnostic approaches to early diagnosis and intervention may exist.

The construction industry has a notable negative impact on the environment; thus, the promotion of the use of timber structures is an alternative to mitigate its effects. The research develops an artificial intelligence-based decision approach in the calculation of timber structures focused on the enhancement of the sustainability of roof structures. Based on the optimization carried out through genetic algorithms and the framework established in Eurocode 5, a general set of equations has been proposed for a laminated timber roof structure. The tool, which determines the most suitable roof structure for each strength class of laminated timber, allows for the determination of the dimensions of beams and purlins and their respective separations in order to minimize wood consumption. The ultimate goal is to offer multiple solutions regarding strength classes and structural designs in order to foster informed sustainable choices that promote efficient use of resources in construction.

Wood is poised to become a material of choice for future construction. When appropriately managed, it is a renewable material with unique mechanical properties. Beyond its inherent sustainability, the use of wood has a crucial role in addressing climate change concerns due a significantly lower energy consumption and emissions during manufacturing and transportation, while simultaneously acting as a carbon sink. Thus, there has been a growing demand for hardwoods for structural applications, including Castanea sativa Mill., the focal point of this investigation. Albeit in a limited capacity, Eurocode 5-2 offers friction coefficients for softwoods, but it falls short for hardwoods which it is a gap to bridge with this research. These coefficients play a critical role in numerical simulations involving friction, enabling the optimization of joints and, by extension, the overall structural integrity. Test samples were evaluated at 18% moisture content, which is typical of Service Class 2, for various orientations of timber-to-timber and timber-to-steel friction. Considering previous friction coefficients at 12% moisture content, the linear variation was evaluated at an intermediate value of 15%. The results provide an experimental database for numerical simulations and highlight the influence of moisture content on the coefficients, which increase linearly along moisture percentages.

Cancer being a multi-factorial disease, a multi-target approach is needed to treat it with minimal side-effects. Therefore, combined use of a proven herbal formula with chemo-therapy could be the better therapeutic. It may maintain homeostasis by synergistically targeting multiple signaling pathways involved in tumorigenesis, thus circumventing recurrence, resistance, and immunosuppression. Here we aim to determine the effectiveness and safety of an FDA-approved herbal formula, SR033 in combination with 5-fluorouracil (5FU) and paclitaxel (PTX). We report chemo-sensitization and chemo-synergy in HeLa and MCF-7 cell lines, immunomodulation of COX-2, PD-L1, VEGF and TGFβ and overall survival in-vitro and in-vivo via oral and topical delivery of SR033. In-vitro, SR033/5FU significantly reverses 5FU and PTX-resistance, lower COX-2, and PD-L1, resulting in TGFβ/ VEGF axis modulation. Furthermore, the study suggests that due to anti-oxidative potential of SR033, oral administration exerts chemo-preventive activity and restores cellular compartment in solid tumor and ascites-bearing mice models. Furthermore, the topical application, SR033L with low-dose 5FU increases survival rate, reduces tumor growth, and completely restores local and peripheral neutrophil-lymphocyte ratio in solid tumor mice model. The study indicates that SR033 could be a strong candidate in combination with low-dose 5FU and PTX for a holistic approach to cancer management.

The described data set contains features from the machine control of a five-axis milling machine. The features were recorded during thirteen series productions. Each series production includes a changeover process in which the machine was set up for the production of a different product. In addition to the timestamps and the twenty recorded features derived from Numerical Control (NC) control variables, the data set also contains labels for the different production phases. For this purpose, up to 23 phases were assigned, which are based on a generalized milling process. The data set consists of thirteen .csv files, each representing a series production. The data set was recorded in a production company in the contract manufacturing sector for components with real series orders in ongoing industrial production.

The 5-hydroxymethylfurfural (HMF) is a six-carbon heterocyclic organic compound with two substituents an aldehyde group and an alcohol group. It is formed from saccharides as a result of two reactions: the Maillard reaction and the caramelization of saccharides. It has both a negative and a positive effect on the human body, which makes it, even more, an attractive research object. The objective of the study was to determine HMF content in honey samples available on the Polish market using three varied methods and compare the results obtained. The methodology used included: two spectrophotometric methods (by White and Winkler) and the HMF determination method based on the LC-MS/MS technique developed uniquely for this study. The determined HMF content in all tested honey samples did not exceed the applicable standard. All results are within the scope of the European Council Directive 2001/110/EC of 20 December 2001, i.e. they do not exceed HMF content in honey, which is 40 mg/kg.

Toxoplasma gondii is a widespread protozoan parasite that infects most warm-blooded animals, and felids can serve as intermediate and definitive hosts. Pathological diagnosis and serological and etiological investigations were conducted on a captive caracal (Caracal caracal) carcass collected from China in 2022. Pathological diagnosis revealed that cardiac insufficiency, pulmonary edema, hepatic failure, and renal insufficiency were the causes of the caracal’s death. A modified agglutination test (cut-off: 1:25) revealed that IgG antibodies against T. gondii were present in the myocardium juice, hydroperitoneum, and hydropericardium (≥1:800). A viable T. gondii (TgCaracalCHn2) strain was isolated from the tissue samples (heart, brain, spleen, and skeletal muscle) of this caracal using a mouse bioassay. The genotype of TgCaracalCHn2 was ToxoDB#5 (Type II variant), as determined by RFLP-PCR. The strain was avirulent in Swiss mice and matched the prediction of ROP18 and ROP5 gene alleles of TgCaracalCHn2 (2/2). Many tissue cysts (203 ± 265) were observed in mice brains after inoculation with TgCaracalCHn2 tachyzoites. ToxoDB#5 is the dominant genotype in North American wildlife, and this is the first documented isolation of T. gondii ToxoDB#5 from China. This indicates that caracals can accelerate the transmission of T. gondii genotypes.

Inosine 5'-monophoaphate (IMP) allows animals to sense umami. Intake of IMP in C57/KsJ-db/db (db/db) mice induced lipohyperplasia causing the liver cirrhosis, however, how to that of in normal mammals injure health is still unclear. Thus, we had investigated that intake of IMP in C57BL/6J mice effected its metabolic functions. We found that intake of 255 M/d IMP in C57BL/6J mice for 4 months induced hyperlipidemia and body fat rate raised. In mechanism, the expressions of ACC1 and phosphorylated ACC2 in hepatocytes were increased though IMP promoting phosphorylation of AMPK. The increased ACC1 promoted the conversion of acetyl-CoA into TG. These TG were transported out of hepatocytes to avoid NAFLD, causing a deficiency of acetyl-CoA in liver, and then the increased phosphorylated ACC2 promoted cytoplasm fatty acids into mitochondria to convert into acetyl-CoA though the fatty acids β-oxidation pathway, causing a deficiency of fatty acids. Therefore, liver enhanced the absorption of exogenous fatty acids, which were converted into TG caused lipohyperplasia. Moreover, intake of IMP in normal mice induced complement system weaken in liver causing mild inflammation. Our data not only alerted that humans avoid excessive intake of IMP, but also provided novel insights into the adipose of metabolic dysfunctions.

Dehydroaromatization of methane (MDA) is of great interest as a promising process for processing natural and associated petroleum gases, the main component of which is methane. The rapid loss of catalyst activity because of coke formation hinders the introduction of the DHA methane process into industry. Therefore, the aim of the research was to find ways to improve Mo/ZSM-5 catalysts for MDA. The paper presents the results of the synthesis of high-silica zeolites of the ZSM-5 type with a microporous and micro-mesoporous structure, the preparation of Mo/ZSM-5 catalysts based on them, and the study of the physicochemical and catalytic properties of the obtained samples during the non-oxidative conversion of methane into aromatic hydrocarbons. Zeolite catalysts were investigated by IR spectroscopy, X-ray diffraction, TPD-NH3, SEM, HR-TEM, N2-adsorption. It was found that the addition of carbon black at the stage of synthesis of zeolite type ZSM-5 does not lead to structural changes, the obtained samples have a crystallinity equal to 100%. The creation of the micro-mesoporous structure in Mo/ZSM-5 catalysts lead to an increase in their activity and stability in the process of methane dehydroaromatization. The highest conversion of methane is observed on a 4.0%Mo/ZSM-5 catalyst prepared based on of zeolite synthesized using 1.0% carbon black, and is 13.0% in 20 minutes of reaction, while the benzene yield reaches 7.0%. It has been shown by HR-TEM that a more uniform distribution of the active metal component is observed in a zeolite catalyst with a micro-mesoporous structure than in a microporous zeolite.

Pancreatic cancer exhibits a poor prognosis due to the lack of early diagnostic biomarkers and the resistance to conventional chemotherapy. CD44 has been known as a cancer stem cell marker, and plays tumor promotion and drug resistance in various cancers. Especially, the splicing variants are overexpressed in many carcinomas, and play essential roles in the cancer stemness, invasiveness or metastasis, and resistance to treatments. Therefore, the understanding of each CD44 variant (CD44v) function and distribution in carcinomas is essential for the establishment of CD44-targeting tumor therapy. In this study, we immunized mice with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells, and established various anti-CD44 monoclonal antibodies (mAbs). One of the established clones (C44Mab-3; IgG1, kappa) recognized peptides of the variant 5-encoded region, indicating that C44Mab-3 is a specific mAb for CD44v5. Moreover, C44Mab-3 reacted with CHO/CD44v3–10 cells or pancreatic cancer cell lines (PK-1 and PK-8) by flow cytometry. The apparent KD of C44Mab-3 for CHO/CD44v3–10 and PK-1 was 7.1 × 10−10 M and 1.9 × 10−9 M, respectively. C44Mab-3 could detect the exogenous CD44v3–10 and endogenous CD44v5 in western blotting, and stained the formalin-fixed paraffin-embedded pancreatic cancer cells, but not normal pancreatic epithelial cells in immunohistochemistry. These results indicate that C44Mab-3 is useful for detecting CD44v5 in various applications, and expected for the application of pancreatic cancer diagnosis and therapy.

Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancer have been masked by high drug toxicities, adverse reactions, and resistance. Using nanocarriers like liposomes to overcome these unwanted effects has become very popular. This study aimed to formulate 1,3-bis tetrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and evaluate the stability, MFU release kinetics, in vitro and in vivo anticancer activities, and biodistribution. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticle (Rh0-LnP) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP) as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnP in vivo using inductively coupled plasma mass spec-trometry (ICP-MS). The mean hydrodynamic diameters of the blank LnP and Zhubech were 90.0 ± 0.65 nm and 124.9 ± 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4o C and 25oC for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R2 value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroids (IC50Zhubech = 3.4 ± 1.0μM vs IC50MFU = 6.8 ± 1.1μM) and organoids (IC50Zhubech = 9.8 ± 1.4μM vs IC50MFU = 42.3 ± 1.0μM) culture models. Confocal imaging confirmed high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor efficacy studies in PDX bearing mouse model revealed more than 9-fold decrease in mean tumor volumes in Zhu-bech treated (108 ± 13.5 mm3) compared to 5-FU treated (1,107 ± 116.2 mm3) animals respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

Multiple studies have shown that hospital settings are poorly cleaned during terminal cleaning. The adequacy of these cleaning methods has been undermined by presence of multi drug resistant bacteria on hospital surfaces. This case is even more serious in developing countries leading to health care- associated infections that pose a great threat to patients, visitors and health care providers in hospital settings.This study used various microbiological techniques to test for antibiotic susceptibility profiles of bacteria present at Thika Level 5 Hospital surfaces, Kenya. A simple random cross sectional study was performed, with a total of 85 samples being collected from five different sites. The sites included male and female wards, health care personnel offices, latrine, and kitchen surfaces. Samples were collected using sterile swabs, dipped in normal saline, and transported to the laboratory within 2Hours for processing.Of the 85 plates cultured, 47 plates showed bacterial growth (55%) on selective media with a significant P value of 0.0357. Seven different species of bacteria were identified biochemically from all sites, Escherichia coli was the most abundant species (28%), and the least was Salmonella typhii (5%). Multiple drug resistance was common in the different bacteria identified. All isolates were resistant to chloramphenical and susceptible to gentamycin. The most resistant microorganism was Staphylococcus aureus (50%), and the least resistant microorganism was Klebsiella pneumoniae (12.5%). The antimicrobial resistant bacterial species identified in this study have been documented to cause serious health care associated infections. These results present a significant public health concern because there is a possibility of patients, staff and visitors contacting nosocomial infections when they come into contact with surfaces at Thika Level 5 Hospital surfaces, Kenya.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

This article explores the concept of sustainable leadership in the digital era and the role of technology in promoting environmental sustainability. As the world becomes increasingly interconnected through digital advancements, leaders are facing new challenges and opportunities to address environmental concerns. This article examines the key characteristics of sustainable leadership and discusses how technology can be utilized to promote environmental sustainability. It highlights various technological innovations and strategies that leaders can employ to foster a sustainable organizational culture. Moreover, the article discusses potential barriers and limitations of technology in achieving sustainability goals. Overall, it emphasizes the significance of sustainable leadership and technology integration in addressing environmental challenges in the digital era.

A study of the water quality of the Adolfo López Mateos Reservoir (ALMD) was developed through different indicators from a spatial and seasonal perspective. Variables related to the general characteristics of water quality, trophic level and ecological risk were assessed through the water Quality Index (WQI_NSF-BROWN), Trophic State Index (TSI_CARLSON) and the Ecological Risk Index (RI_HAKANSON). Using data from physical, chemical and biological parameters obtained from four sampling points in the ALMD, the water quality was assessed in each model used. The results indicated that the reservoir presents a water quality classified as “medium” (WQI_NSF-BROWN = 70), where significant variations in the concentrations of some parameters are observed. The reservoir showed a general trophic state classified as “Mesotrophic” (TSI_{GENERAL-AVERAGE} = 43.04). The ecological risk analysis achieved the best classification of the methodology, discarding contamination by heavy metals in surface waters. Through this type of applied methodologies will help as decision making tools in the dam, as well as for application in other dams in the region.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

Cowpea (Vigna unguiculata (L.) Walp.) is an important legume cultivated mainly in regions with limited water availability across the African and American continents. Its productivity is significantly affected by environmental stresses. Thaumatin-like proteins (TLPs), which belong to the PR-5 (Pathogenesis-Related 5) protein family, are known to be responsive to both biotic and abiotic stresses. However, their role remains controversial, with some TLPs associated with plant defense (particularly against fungal infections) and others associated with drought response. In this study, we evaluated the structural diversity and gene expression of TLPs in cowpea (VuTLPs) under different stress conditions, including biotic [mechanical injury followed by inoculation with Cowpea Aphid-borne Mosaic Virus (CABMV) or Cowpea Severe Mosaic Virus (CPSMV)] and abiotic (root dehydration). Genomic anchoring of VuTLPs revealed 34 loci encoding these proteins. Neighbor-joining analysis clustered the VuTLPs into three distinct groups. We identified 15 segmental duplication and six tandem duplication gene pairs, with the majority of VuTLP genes found to be under purifying selection. Promoter analysis associated VuTLPs with bHLH, Dof-type, and MYB-related transcription factors, supporting their diverse roles. Diversity in VuTLP function was also observed in their expression profiles under various stress conditions. Gene expression data showed that most VuTLPs are recruited within the first minutes after stress imposition, except in the root dehydration assay, where most transcripts were induced 150 minutes post-stress, a finding also validated by qPCR. Moreover, the data suggest that VuTLPs exhibit functional specialization depending on the stress condition, highlighting their diverse roles and biotechnological potential.

Undernutrition is a significant public health issue in Colombia and globally, influenced by multiple factors. The relationship between food insecurity and acute undernutrition in children has been insufficiently explored. To address this, a descriptive, observational, cross-sectional study was conducted involving 70 children under the age of 5, who presented with moderate to severe acute malnutrition. The study assessed family and child food security using the Latin American and Caribbean Food Security Scale (ELCSA). Analysis of the data revealed that when households face challenges in meeting their basic needs, children are generally the least affected. Caregivers tend to prioritize children's diets, opting to reduce food intake among adults over 18 years of age instead. The causes of malnutrition were explored through the perceptions of guardians, who reported that in 30.2% of cases, malnutrition is linked to inadequate feeding and parenting practices. Specific issues noted by parents included children being too lazy to chew, preferring ultra-processed foods, or refusing to eat altogether. The study found that not all children with acute malnutrition experience food insecurity; in fact, the proportion of children suffering from hunger was very low. The findings suggest that malnutrition in children under 5 years of age is not solely determined by food insecurity but also by other factors such as parenting practices and poor feeding habits. Further research is needed to evaluate food access and quality, particularly in terms of dietary diversity, to better understand the needs of each population. Such studies will be essential in guiding public health interventions aimed at preventing, managing, and addressing malnutrition in children.

The structure verification of 5'-oxospiro-(fluorene-9,4'-imidazolidine)-2'-thione by NMR was reported. For the aim, 2D NMR techniques including 1H-1H COSY, HMQC and HMBC experiments were used to assist the assignment of the 1H and 13C chemical shifts for the corresponding structure. The mutual interpretation of the 1D and 2D NMR spectra ensured a complete and an accurate 1H and 13C NMR data assignment for 5'-oxospiro-(fluorene-9,4'-imidazolidine)-2'-thione.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Autism has been described as a gastrointestinal and neurological condition that is represented by impairments in language and social situations. Recently reported increases in the occurrence of Autism Spectrum Disorder (ASD) have resulted in increased research into the environmental differences between areas with a high occurrence, as in the “Western” diet populations, and a more locally derived diet population, wherein the rate appears to be significantly less. Thirty autistic children (USA) ages 6 to 21, were sampled at three different intervals: prior to any intervention, post-xylitol intervention, and post-probiotic intervention. The sampling consisted of buccal swabs for MITOSWAB testing, and saliva for metatranscriptomics to determine the entire range of microorganisms and the metabolome. In addition, a “Blue Zone” subject component that included 30 Colombian children, ages 6-16, and who were healthy and within normal behavior standards, also had buccal swabbing and salivary sampling performed for comparison along with 30 healthy (no history medications, illnesses, or behavior issues) USA children matched for age and gender. Saliva samples were analyzed metatranscriptomically and artificial intelligence was utilized to discern important differences in the microbiome that included bacteria, archaea, fungi, and viruses, and microbial functions. Significant differences were noted, and seen in the temporal data, demonstrating shifts that may have been precipitated by the interventions, with both the probiotics and the polyols. Particular bacterial strains were significantly more prevalent in the autism subject group including a strain that reduces neurotransmitters by enzymatic degradation. This provided supporting evidence to the hypothesis that the occurrence of autism may also be influenced by low Gamma Amino Butyric Acid (GABA) levels during development. Also, of interest was the un-expected finding that verbal skills dramatically increased in 6 of the 30 ASD subjects following xylitol supplementation.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

In May 2022, WHO reported an outbreak of Mpox in several European countries which were previously Mpox free. Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in Central and West Africa. The sudden emergence of Mpox outside Africa and its subsequent rapid spread lead the WHO to declare the outbreak as Public Health Emergency of International Concern. As of May 15, 2023, a total of 87,704 confirmed cases and 140 deaths had been reported from 111 countries and territories worldwide. Looking back on this outbreak one year later, several important questions have arisen. Here, we address these questions using the classic five Ws: What, When, Where, Who and Why? We discuss these questions and outline what needs to be done to prevent, or at least minimize, outbreaks from emerging and re-emerging viral infection.

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was further interacted with calcium ions, to realize enhanced pH-responsive nanocarrier for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, then polymerization of acrylic acid was proceeded. After adding calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecules-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive targeted nanocarriers in the field of medical treatment.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and in several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviors. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out (KO) mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

To characterize the mechanisms by which the highly-conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on exoc5 (aka sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5-/- zebrafish showed smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post fertilization, loss of rod and cone opsins were observed in zebrafish Tg:exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function, and loss of visual photoreceptor pigments. This retinal phenotype in Exoc5-/- mice was present at 20-weeks, and the phenotype was more severe at 27-weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. As RPE cells are “downstream” of photoreceptor cells in the visual process, these data suggest exocyst-mediated retrograde communication and dependence between the RPE and photoreceptors.

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat despite advances in pharmacotherapeutic approaches in the field. Therefore, this study investigated the erectogenic effect of the methanolic extract of Maytenus procumbens roots on type 2 diabetes in rats. The fructose-streptozotocin model was used to induce type 2 diabetes-linked ED in male rats. The sexually active male Sprague Dawley rats were randomly divided into two major groups; normal group and high fructose fed group for 120 days. After 120 days, the high fructose fed group rats were given a single intraperitoneal injection of a freshly prepared streptozotocin solution (30 mg/kg). The diabetic ED rats were orally administered with the extract at 250 mg/kg, daily for 28 days. The serum, brain and penile tissues were removed for biochemical analysis and protein expression. Increased testosterone level, mounting frequency, reduced blood glucose level and serum fructosamine content was observed after 28 days of treatment in diabetic rats. Methanolic extract also exhibited an inhibitory effect on arginase, AChE, and ACE activities. The crude extract further downregulated proteins PDE-5, RhoA and increased expression of eNOS in the diabetic ED treated rats. The results obtained indicate that the methanolic extract of Maytenus procumbens roots ameliorates erectile dysfunction in type 2 diabetes-induced erectile dysfunction in rats.

Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism during fasting. The wild-type (WT) and LRH-1 liver-specific knockout (LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. During fasting, the LRH-1 LKO mice showed greater accumulation of triglycerides in the liver compared to that in WT mice. Interestingly, LRH-1 LKO liver decreased the perilipin 5 (PLIN5) expression and genes involved in β-oxidation. Additionally, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed to analyze the PLIN5 promoter sequence, which revealed −1620/−1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immuno-precipitation assays. Moreover, fasted WT primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted LRH-1 LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs and manage the cellular needs.

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n=6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n=6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) and [3H]Cimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.4% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (-15.21% to -50.19%). These differences were statistically significant in the hippocampus for all radioligands and in PFC for [3H]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in hippocampus (+9.24%) and PFC (+6.1%) whereas there were no longer any differences in 5-HT2AR density. Our findings suggest that psilocybin’s antidepressive actions are linked to increased persistent synaptogenesis and possibly also to an acute decrease in 5-HT2AR density.

After the increasing number of SARS-CoV-2 infections all over the world, researchers and clinicians are struggling to find a vaccine or innovative therapeutic strategies to treat this viral infection. The SARS-CoV infection that occurred in 2002, MERS and other more common infectious diseases such as HCV, led to the discovery of many RNA-based drugs. Among them, siRNAs and antisense LNAs have been demonstrated to have effective antiviral effects both in animal models and humans. Owing to the high genomic homology of SARS-CoV-2 and SARS-CoV (80-82%) the use of these molecules could be employed successfully also to target this emerging coronavirus. Trying to translate this approach to treat COVID-19, we analyzed the common structural features of viral 5’UTR regions that can be targeted by non-coding RNAs and we also identified miRNAs binding sites suitable for designing RNA-based drugs to be employed successfully against SARS-CoV-2.

CrHZSM-5 was placed in an electric field with appropriate strength in a quartz packed bed reactor with CO2 as oxidant to analyze its catalytic activity. Olefin yield increases with decrease in band gap since lattice oxygen mobility increases by reducing band gap. Fermi level change at the catalyst surface affects the catalytic activity. One way to change Fermi level is use electric field. In high voltage electric field, energy band was curved, bending of the energy band promoted the activity and Fermi level position is increasing. The CCD experiments were carried out with Design-Expert 7.3 software to determine the interaction between four operating variables, namely: temperature, electrical current, gap distance and metal loading. The levels of the independent variables were: temperature (550-700 °C), electrical current (0-12 mA), gap distance (6-14 mm), metal loading (0.5-7.5 %wt.). The conversion of LPG (Liquefied petroleum gas) was greatly increased by weak and effective application of an electric field to the catalyst bed. The obtained results indicated that the maximum yield value (46.94%) can be achieved under 673.66 °C, input electrical current of 11.01 mA, gap distance of 6.55 mm and metal loading of 3.98 wt.%.

Lung cancer is almost the most common cause of cancer death in the world. Clinically, the conventional therapy to eradicate the cancer cells is chemotherapy but a better drug remains required. In this study, the effects of three bufadienolides, kalantuboside B, kalantuboside A and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung cancer cells. Contrary to the apoptosis-promoting activity in other cancer cells, these three bufadienolides did not induce apoptosis in CL1-5 cancer cells. Instead, they activated an autophagy pathway, as indicated by the increase of autophagosomes formation. The induction of autophagy by these three bufadienolides was demonstrated to link to down-regulation of p-mTOR as well as up-regulation of LC3-II, ATG5, ATG7, Beclin-1. Moreover, among these three compounds, kalantuboside B in which a monosaccharide is attached at the bufadienolide aglycon, exhibited a better autophagy induction. Our findings revealed an alternative mechanism of drug action by bufadienolides in lung cancer cells and provided evidence for the possibility of treating highly metastatic human lung cancer through an autophagy pathway.

Lower respiratory infections (LRI), upper respiratory infections (URI), and nutritional deficiency (ND) in under-5 children from low-middle-income countries has been at a high level for decades, despite efforts that have been realized in some countries. The study used data extracted from the global burden of diseases (GBD) to analyze the trends behavior between 1990 and 2019, and evaluate their association with maternal factors. Between 1990 and 2019, the incidence of LRI decreased between 1.2 percent and 1.3 percent (1.2-1.3%) in different female age groups, and by nearly 1 to 1.3% in those of the male gender. The incidence of URI did not decrease (0.0%) in any of their age groups. ND incidence declined around 0.7 to 4.9% in the under-5 children. LRI declined mostly in the female age groups (1.2 to 1.3%), while ND decreased more in the male gender (0.9 to 4.9%). Maternal risk factors were strongly associated to the incidence of the three conditions with over 90 percent. Maternal prevalence of HIV/AIDS and tuberculosis positively impacted the incidence of LRI, URI, and ND in Chadian under-5 children. Although the incidence of LRI and ND declined, URI incidence remained steady between 1990 and 2019 in Chadian under-5 children. To improve the health and provide a healthy growth of under-5 children, the maternal prevalence of HIV/AIDS and tuberculosis infection should be strongly addressed for a prompt accomplishment of the sustainable development goals.

In this contribution, the propylamine-functionalized cellulose (Cell-Pr-NH2) was employed as the catalyst in the three-component reaction between hydroxylamine hydrochloride, various type of aryl/heteroaryl aldehydes, ethyl acetoacetate/ethyl 4-chloroacetoacetate/ or ethyl 3-oxohexanoate. The results of these experiments were the formation of 3,4-disubstituted isoxazol-5(4H)-one heterocycles. The desired five-membered heterocyclic compounds were obtained in good to high yields at room temperature. The investigation of different solvents led us to the conclusion that water is the best solvent to perform the current one-pot, three-component reactions. Attempts to find the optimum catalyst loading clearly showed that 14 mg of Cell-Pr-NH2 seems to be sufficient to carry out the reactions. This method has highlighted some principles of green chemistry including less waste generation, atom economy, use of water as an environmentally friendly solvent, and energy saving. Purification without chromatographic methods, mild reaction conditions, simple work-up, low-cost reaction medium, saving time, and obtainable precursors are other notable features of this one-pot fashion.

RNA-seq faces persistent challenges due to the ongoing expanding array of data processing workflows, none of which have yet achieved standardization to date. It is imperative to determine which method most effectively preserves biological facts. Shannon entropy serves as a tool for depicting the biological status of a system. Thus, we assessed the measurement of Shannon entropy by several RNA-seq workflow approaches, employing RPKM and median normalization on paired samples of 475 TCGA RNA-seq datasets spanning eight different cancer types with 5-year overall survival rates ranging from 30% to 98%. Our analysis revealed that the RPKM normalization coupled with a threshold of log2 fold change ≥1 for indentifying differentially expressed genes, yielded the best results with a correlation coefficient of 0.91. We propose that Shannon entropy can serve as an objective metric for refining the optimization of RNA-seq workflows.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

This is a SARS-CoV-2 seroepidemiological study in pediatric population(0-16 years) during BA.5 Omicron predominance period in Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies(Abs-N), representing natural infection during three sub-periods of BA.5 predominance: 01/05/2022-31/08/2022(period A), 01/09/2022-31/12/2022(period B) and July 2023(period C) and epidemiological data were collected. Additionally in period C Abs-N seronegative samples were tested for SARS-CoV-2 spike antibodies(Abs-S). A total of 878 children were tested (males:51.3%) with median age(IQR): 108(36-156) months and seropositivity during the 3 subperiods was: A:292/417(70%), B:288/356(80.9%), C:89/105(84.8%), P-value<0.001. SARS-CoV-2 seropositivity increased for from period A to C for 0-1-year (P-value: 0.044), 1-4 years (P-value: 0.028) and 6-12 years children (P-value: 0.003). Children 6-12y had the highest seroposi-tivity rates in all subperiods (A: 77.3%, B: 91.4% and C: 95.8%). A significant correlation of monthly SARS-CoV-2 median antibody titers with monthly seropositivity rates was detected (rs:0.812, P-value:0.008). During period C, an additional 12/105 (11.4%) Abs-S seropositive and Abs-N ser-onegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The increased SARS-CoV-2 seropositivity detected in current seroepidemiology study illustrates a high exposure rate during BA.5 predominance period. These data could guide public health decisions regarding immunization strategies and protection measures.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

In the realm of the five-category classification endeavor, there has been limited exploration into applied techniques for classifying Arabic text. These methods have primarily leaned on singletask learning, incorporating manually crafted features that lack robust sentence representations. Recently, the Transformer paradigm has emerged as a highly promising alternative. However, when these models are trained using single-task learning, they often face challenges in achieving outstanding performance and generating robust latent feature representations, especially when dealing with small datasets. This issue is particularly pronounced in the context of the Arabic dialect, which has a scarcity of available resources. Given these constraints, this study introduces an innovative approach to dissecting sentiment in Arabic text. This approach combines Inductive Transfer (INT) with the Transformer paradigm to augment the adaptability of the model and refine the representation of sentences. By employing self-attention SE-A and feed-forward sub-layers as a shared Transformer encoder for both the five-category and three-category Arabic text classification tasks, this proposed model adeptly discerns sentiment in Arabic dialect sentences. The empirical findings underscore the commendable performance of the proposed model, as demonstrated in assessments of the Hotel Arabic-Reviews Dataset, the Book Reviews Arabic Dataset, and the LARB dataset.