Understanding of interlinked metabolism of guard cell (GC) and mesophyll cell (MC) and their roles in stomatal movement will help in designing crop plants with higher water use efficiencies. Although, previous constraint-based modelling and analyses correctly predicted some known metabolic patterns of isolated C 3 MC, GC and Crassulacean Acid Metabolism (CAM) MC, detailed analysis of combined metabolism of GC and MC and their quantitative estimations in both C 3 and CAM are still awaiting. We integrate stomatal opening, gaseous exchange and GC-MC metabolism in our constraint-based six-phase diel combined metabolic model and simulate this model to predict the temporal differential flux distributions of GC and MC metabolisms. In addition to previously predicted results, analysis of this new two-cell model successfully shows higher activities of some experimentally observed C 4-like enzymes such as PEPC, MDH, ME etc., in GC compared to MC in C 3, the possible storage patterns of the osmolytes like K +, malate 2-, sucrose etc., in CAM GC. Results also show temporally different patterns of starch synthesis and accumulation, ATP production and utilization in GC and MC of C 3 and CAM. It is a significant step towards understanding and quantitative estimation of the whole leaf tissue metabolism linking gaseous exchange with environment.

The performance of invertebrate herbivores in grasslands can be influenced by climate warming, but there is a lack of experimental evidence, particularly in high elevation areas. We conducted two complementary experiments to investigate the effect of experimental warming on the performance of the grassland caterpillar Gynaephora alpherakii, a notorious pest species in the alpine Tibetan meadow. The first field experiment examined the effect of warming (non-warmed vs. warmed) on the feeding behavior, growth and development rate of the caterpillars. The second chamber experiment explored the relationship between temperature and caterpillar appetite, excrement mass, respiration rate or change of caterpillar weight. Results show that warming significantly decreased fresh body mass of caterpillars by 27.5%, cocoon volume by 61.1%, and egg production per female moth by 26.9 % at the end of the field experiment. Warming did not affect cocooning time but significantly increased feeding time of caterpillars during the field experimental period. The independent chamber experiment revealed a significant and positive correlation between caterpillar appetite, excrement mass, respiration rate, and temperature. However, except the first examination, there was a significant negative correlation between changes in caterpillar weight and temperature. Stepwise regression analysis indicated that excrement mass had the greatest influence on caterpillar weight. The weight loss of caterpillars to warming might thus be attributed to elevated metabolic rates at higher temperatures, and the behavioral adaptations failed to compensate for the physiological-induced weight loss. These findings suggest that climate warming can modify the performance and thus the fitness of invertebrate herbivores in high elevation areas.

Background: The crosstalk between the pulmonary artery smooth muscle cell(PASMC) and fibroblast had influenced the vascular inflammation, the role of NDRG1 in vascular inflammation still need to be explored further.Methods:CCK8 assay was used to investigate the effect of NDRG1 overexpression on the proliferative capacity of PASMCs, quantitative reverse transcription PCR(rt-qPCR) was used to investigate the role of NDRG1 overexpression on the expression of inflammatory factors in PASMCs, and EDU assay and scratch assay were used to investigate the effect of PASMCs with overexpression of NDRG1 on the proliferative and migratory capacity of fibroblasts.Results:CCK8 assay of PASMCs overexpressing NDRG1 showed a significant increase in proliferative capacity compared to controls, and PASMCs with knockdown of NDRG1 showed a significant decrease in proliferative capacity. In addition, rt-qPCR assay suggested that the expression of inflammatory factors IL-6 and TNF was significantly elevated in PASMCs overexpressing NDRG1( P<0.05). Compared with control fibroblasts, the expression of TNF-α and SMA in fibroblasts cocultured with overexpressing NDRG1 were significantly elevated( P<0.05). Besides, the expression of IL-6, IL-10 were not significantly( P>0.05), and the proliferation and migration abilities were significantly increased( P<0.05).Conclusions:NDRG1 might had played important roles in the vascular inflammation.

In this work, the existence and uniqueness of the solution to the semiperiodic boundary problem for a third-order partial differential equation are obtained. Estimates for the solution and its derivatives have been established. To achieve this, a special substitution is used to reduce the third-order equation to a system of ordinary differential equations (ODE) and functional relations. The unique solvability of the resulting periodic boundary value problem for the ODE system is proven using the parameterization method.

Background: While the global childhood leukemia burden has declined since 1990, it remains the leading cause of childhood cancer mortality. Disparities in outcomes are stark, with high-income countries achieving significantly higher survival rates compared to resource-limited settings. This underscores the critical role of healthcare quality. Methods: We analyzed data on childhood leukemia (aged 0-14) from the Institute for Health Metrics and Evaluation Global Burden of Disease project (1990-2021), including incidence, mortality, prevalence, and other health metrics. To assess the Quality of Care Index (QCI), we implemented a four-step process involving data acquisition and cleaning, optional data reduction, calculation of secondary measures and application of Principal Component Analysis (PCA), and finally data visualization. PCA identified a single component as the QCI, with higher scores indicating better quality of care. Results: Childhood leukemia incidence, mortality, and Disability-Adjusted Life Years (DALYs) declined globally, but regional disparities persist. High-middle Sociodemographic Index (SDI) countries have the highest incidence, while low SDI settings have the highest mortality and DALY rates. Global QCI average is 67.8, with variation between regions and SDI levels. High SDI countries have the highest QCI, while low SDI settings have the lowest. QCI decreases with age, and gender distribution is relatively equal globally, except in low and low-middle SDI settings. Conclusion: Despite global progress in reducing childhood leukemia, significant healthcare disparities persist. Future efforts must prioritize addressing these inequities, ensuring equitable access to quality care, and eliminating disparities based on SDI, age, and gender.

Ransomware attacks have become one of the most pervasive threats in cybersecurity, capable of inflicting severe damage on both individual and enterprise systems by encrypting valuable data and demanding ransom payments. The traditional reliance on static signatures and heuristic-based detection methods has proven inadequate in addressing the sophisticated and rapidly evolving nature of modern ransomware variants. A novel approach is introduced through process memory analysis, enabling the detection of ransomware in real-time without the need for predefined signatures. By monitoring memory access patterns and using machine learning classifiers, the system identifies anomalous behaviors that distinguish ransomware from benign processes with a high degree of accuracy. The proposed system's robustness is demonstrated through rigorous testing, revealing its efficiency in handling large-scale memory operations while maintaining low false positive rates. Furthermore, the research contributes to the field of ransomware detection by introducing a scalable, machine learning-driven framework capable of adapting to new and previously unseen ransomware variants.

Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications. PEA primarily exerts its effects through interaction with its primary receptor PPAR α, this interaction influences pain signalling pathways and neuroinflammatory processes by modulating the synthesis of pro-inflammatory cytokines, mast cell degranulation, microglial activation, and decrease of oxidative stress. PEA’s interaction with endocannabinoid receptors decreases the inflammatory cytokine and chemokine production and thereby a descending pain sensation. The pharmacological and pharmacokinetic characteristics of PEA are examined in this paper, along with its potential for efficiency when used in in combination additional therapies in a variety of neurodegenerative disease models, including multiple sclerosis, Parkinson’s disease, and Alzheimer’s. Experimental evidence shows that PEA not only reduces pain and inflammation but also lowers the need for higher dosages of other drugs hence minimizing the risk of drug toxicity. The bioavailability of PEA has been enhanced by recent technological developments, which emphasize continuous research efforts to maximize PEA’s therapeutic potential in pain treatment and associated medical sectors.

This is a commentary on the manuscript authored by Stadter P, Keller K. Atrial Adaptations in Athletes Heart. Echocardiography. Sep 2024;41(9):e15931. doi:10.1111/echo.15931

High risk PFO-associated stroke: Proposed algorithm for better risk stratificationPetronela Cristina Chiriac1†, PhD, Anca Dumitrescu Bordianu2†, MD, Mariana Floria 1,3, MD, PhD1 Internal Medicine Clinic, ”Sf. Spiridon” Emergency Clinical Hospital Iasi, 700111, Romania.2 Vascular Surgery Clinic, ”Sf. Spiridon” Emergency Clinical Hospital Iași, 700111, Iasi, Romania.3 Faculty of Medicine, Department of Internal Medicine, University of Medicine and Pharmacy ”Grigore T. Popa”, 700111 Iasi, Romania.† Both authors contributed equally.Running title: PFO-associated strokePetronela Cristina Chiriac: chiriac.cristina@spitalspiridon.ro;Anca Dumitrescu Bordianu: bordianu.anca@d.umfiasi.ro;Mariana Floria: floria.mariana@umfiasi.ro; https://orcid.org/0000-0002-9465-1503Correspondence : Floria Mariana, Internal Medicine Department, Grigore T. Popa” University of Medicine and Pharmacy, 16th University Iași, 700115, Romania. E-mail: floria.mariana@umfiasi.ro; floria_mariana@yahoo.com

Background: Atopic dermatitis (AD) causes the impact of sleep disorders due to “itching,” is of real harm to society. Recently, the concept of ”gut-skin axis” has gained recognition, however it is still unclear enough. No previous studies had examined whether colitis induce to AD. The aim of this study is therefore to develop the ”gut-skin axis” model such as that colitis induces AD and to explore a treatment for AD by improving gut dysbiosis by using this model. Methods: We used NC/Nga mice with skin barrier fragility, caused the dextran sulfate sodium (DSS)-induced colitis, performed oral treatment of pasteurized Limosilactobacillus reuteri for improving the gut dysbiosis. Result: We found on high sensitivity to DSS-induced colitis in NC/Nga mice. Some months after DSS-induced colitis, AD lesions with “itching” developed spontaneously on bilateral symmetric specific sites, indicating enhanced blood immunoglobulin E and basophils, elevated T-cell helper 17/T-cell regulatory ratio, increased group 2 innate lymphoid cells in enlarged lymph nodes, and increased cutaneous mast cells. Interleukin (IL)-33 enhanced in gut dysbiosis implicated “itching” due to histamine from cutaneous mast cells. In study for a therapy, oral treating pasteurized L. reuteri-solution improved gut dysbiosis and restored AD exacerbated with high IL-33. That indicates protein(s) secreted when L. reuteri die might be a therapeutic target for AD. Conclusions: We found that NC/Nga mice with DSS-induced colitis eventually developed AD without requiring allergens, also identified several gut bacteria related to AD onset and exacerbation, furthermore, showed that improving gut dysbiosis by using pasteurized L. reuteri-solution prevents and cures AD.

Mihos and coworkers present an interesting report on the impact of apical aneurysm in patients with apical hypertrophic cardiomyopathy (ApHCM). They reference the literature that shows it occurs in 10-15% of patients with ApHCM and that its presence confers a 3-fold increase in HCM-related death or life-saving aborted HCM-related events, and that it is considered a marker of increased risk of sudden death1-2. Their study shows differences in myocardial work efficiency and global wasted work between patients with and without aneurysms. The question is whether the aneurysm caused the differences or are the aneurysms caused by the differences?

Thanks to impressive advances in the field of oncology over the last thirty years, there has been a dramatic rise in cancer survivors. Nowadays, the risk of dying from cardiovascular disease exceeds cancer-related mortality in this population. Coronary artery disease (CAD) is a major problem due to shared risk factors, an ageing population and in many cases induced and/or accelerated by antitumoral treatment during and even decades after the end of cancer therapy. On the other hand, the presence of CAD at the timepoint of cancer diagnosis largely increases the risk of any cancer therapy related cardiovascular toxicity (CTR-CVT). It is therefore of outermost importance to detect CAD before, during, and after certain types of chemo-, molecular-, and radiotherapy. Multimodality cardiovascular imaging plays a central role in this fragile population where individual risk stratification and multidisciplinary decision making is critical.

Background: Macrophages, as one of the most abundant immune cells in the lung, has drawn great attention in allergic asthma. Currently, most studies emphasize on M2 polarization bias. However, the function of macrophages in allergic asthma is still controversial. IL-9 contributes to the development and pathogenesis of allergic airway inflammation. We sought to investigate the IL-9-producing macrophage subset and its role in allergic asthma. Methods: The model of OVA-induced allergic airway inflammation was employed to evaluate IL-9 production in macrophages of lung tissues. We used 22 cytokines or stimuli to screen for IL-9-producing mouse macrophage subset in vitro, and real-time PCR, flow cytometry, ELISA, immunofluorescence and RNA-seq to explore the M(IL-33+IL-2) subset. Mice with Lyz-IL-33 receptor conditional knockout and adoptive transfer M(IL-33+IL-2) were used to characterize the potential roles of M(IL-33+IL-2) in allergic airway inflammation. Results: We identified a unique pathogenic IL-9-producing macrophage subset in OVA-induced allergic airway inflammation. We found that only IL-33 significantly induced IL-9 production in mouse macrophages, and IL-2 collaborated with IL-33 to promote macrophages to produce IL-9, referred to as M(IL-33+IL-2). Importantly, human monocyte-derived macrophages produced IL-9 after IL-33 and IL-2 stimulation. Using mice with Lyz-IL-33 receptor conditional knockout and adoptive transfer of M(IL-33+IL-2), we found that M(IL-33+IL-2) significantly promoted pathogenesis in OVA-induced allergic airway inflammation. M(IL-33+IL-2) subset has a distinctive gene expression profile with high expression of cytokines and M(IL-33+IL2) polarization is dependent on JAK2-STAT3-IRF1 pathway. Conclusions: The identification of M(IL-33+IL-2) subset extends the diversity and heterogeneity of macrophage subsets, and may offer novel therapeutic strategies for treatment of allergic inflammation.

A document by Camilla Grenga. Click on the document to view its contents.

Key clinical message

Title PageManuscript type Case Report

In a world where habitats are degrading and the climate is warming and becoming increasingly unpredictable, biodiversity conservation efforts and funding remain grossly inadequate. There is a clear need to shift from preserving small, remnant populations to a model of genetically connecting populations that recreate larger and more diverse populations in climate-secure environments. This is crucial to harness key evolutionary processes to promote species’ ability to adapt to changing environments and to increase the likelihood of population persistence. Here, we use the endangered Macquarie perch (Macquaria australasica) as a case study to develop a genetic strategy for metapopulation management aimed at promoting population growth and persistence. Macquarie perch habitat has been highly fragmented and remaining habitat is at risk of catastrophic degradation due to climate change. We integrate results of new and existing genetic analyses to illustrate how genetically depauperate populations can benefit from admixture, and how the outcomes of management interventions can be quantified through genetic monitoring. We also develop the pipeline JeDi (https://github.com/drobledoruiz/JeDi) for estimating unbiased genetic heterozygosity for individuals and populations (nucleotide diversity) from reduced-representation genome sequencing data. We use this pipeline to estimate baseline data for monitoring of Macquarie perch populations and show that combining two genetic sources of migrants during population restoration resulted in doubling of nucleotide diversity compared to either source. Genetic diversity estimated using our pipeline is comparable across studies, datasets and species, and suitable for evaluating the rate of global biodiversity change.

Background: Inappropriate penicillin skin testing practices can worsen allergy mislabelling and antimicrobial resistance. This issue is likely more pronounced in Mainland China due to mandatory pre-emptive penicillin skin testing prior to any penicillin prescriptions. In contrast, Hong Kong follows guidelines more aligned with international recommendations on penicillin allergy testing. This study aimed to explore the disparities in drug allergy labelling, penicillin consumption, and antimicrobial resistance between Mainland China and Hong Kong. Methods: This multi-centre, real-world study analyzed drug allergy label prevalence, antibiotic use, and AMR between 2018 to 2022 in Mainland China and Hong Kong. Results: Penicillin allergy labels were significantly higher in Mainland China (47.13%) compared to Hong Kong (21.57%, p<0.01). Penicillin consumption was lower in Mainland China, where antimicrobial resistance to amoxicillin-clavulanate was also lower. Penicillin allergy delabeling rates were significantly higher in Mainland China (99.26%) compared to Hong Kong (93.13%, p=0.03). Conclusion: Significant differences in drug allergy labeling and antibiotic use between Mainland China and Hong Kong highlight the impact of non-evidence-based penicillin skin testing practices in Mainland China. Urgent reforms are needed to adopt international guidelines and reduce allergy mislabeling.

Biofilms are found in diverse environmental settings and are considered to be responsible for various recalcitrant infections. One characteristic feature of biofilms is resistance to antibiotics, which is the leading cause of recurrent infections and treatment failure. Eradicating the biofilms necessitates the need for agents with promising anti-biofilm potentials. In the present study, the secondary metabolites of the fungal endophyte Cephalotheca foveolata (N11) isolated from the woody tissues of the medicinal plant Teucrium stocksianum were investigated for their antibiofilm potential against the test organisms. For evaluating the antibiofilm activities, in-vitro assays including biofilm inhibition and eradication assays were employed. The bioactive metabolites of the N11 strain exhibited the highest biofilm inhibition and eradication potential of 87.62% and 79.22% respectively against S. epidermidis. The results were further validated by light microscopy and confocal laser scanning microscope which revealed considerable distortion of the biofilm architecture by test agents. Besides, the effect of secondary metabolites on biofilms of test strain was also observed using Raman spectroscopy. The Raman spectra of treated biofilms exhibited a significant reduction in the intensities of the peaks indicating the denaturation and conformational changes in biomolecules. Furthermore, the partial purification of antibiofilm metabolites of N11 was carried out using solvent extraction following TLC and silica column with further characterization done using FTIR. These findings highlight the remarkable potential of bioactive secondary metabolites of endophytic fungi associated with Teucrium stocksianum in disrupting the biofilms thus suggesting that these metabolites can be exploited for manufacturing effective agents against biofilm-associated complications.

Good brain health plays a significant role in an individual’s well-being and profoundly impacts the collective economy and society. Brain development does not stop at birth and some aspects continue throughout childhood and adolescence, allowing the full development of cognitive functions. Different determinants related to physical health, healthy environments, safety and security, life-long learning, and social connection as well as access to quality services influence the way our brains develop, adapt, and respond to stress and adversity. Ongoing progress in neurobiology and cognitive neuroscience allow the design of better prevention and intervention strategies to help avoid brain deficits and/or limit their impact and maintain brain health. The European Brain Council (EBC) convened an expert meeting during the FENS Forum 2024 to address youth brain health challenges. In recent years, the importance of brain health has garnered significant attention across scientific, medical, and policy-making communities. While much focus has traditionally been on neurodegenerative conditions affecting the elderly, a paradigm shift towards prioritizing brain health in youth is both timely and necessary. This shift can profoundly impact individual lives and society, necessitating an interdisciplinary approach that brings neuroscience to the forefront of public health and informs evidence-based policy. The topic is of utmost importance as EBC launched this year a new campaign on No Health Without Brain Health rallying support with its member organisations and the wider brain community for the increased prioritization of brain health on EU health and research agendas.

A document by Daniel Estevez-Barcia. Click on the document to view its contents.

            Habitat restoration is a promising strategy to counteract wild bee declines, and consists of repairing degraded habitats and reestablishing native plant communities. To understand the effects of restoration on bees, we investigated bees and plants at three coastal restoration sites in California. We hypothesized that bee communities would vary depending on plant communities, and native plants would be important drivers of bee community composition. We collected 2,017 bees across 37 species and found 320 plant species. Bee communities were similar across all sites despite significant differences in plant communities, which may be explained by high floral diversity at all sites. Flowering native plants, and one non-native plant, were identified as significant drivers of bee community structure, highlighting the importance of prioritizing native plants in restoration projects to support diverse and resilient wild bee populations.

Hypothesis regarding The propagation of electromagnetic waves through spacetime I have long wondered by what mechanism electromagnetic waves are propagated through spacetime. A wave requires a medium to be transmitted, yet space is without any material medium. What could be the conduit by which these waves are propagated? Can we find an analogy.

Edible orchids are increasingly threatened by unsustainable use in their natural habitats. Several studies highlight the need for propagation to counter this threat. However, a critical gap persists in understanding the environmental conditions that support these species in Malawi. This study aimed to identify potential habitats suitable for propagating edible orchids, focusing on Disa engleriana, to enhance ex-situ conservation efforts. Present and future environmental data were sourced from WorldClim. Species occurrence data was obtained during field surveys and existing dataset. Using MaxEnt, continuous habitat suitability for D. engleriana was modeled based on presence-only occurrence data, Bioclim variables, and elevation. The integration of ArcGIS allowed for a detailed analysis, reclassifying the continuous suitability map into suitable and unsuitable habitats. The results of the study show the most suitable habitats align with the boundaries of protected areas, emphasizing their critical importance in conservation planning. Majority of orchid harvesters live near these protected areas, therefore, engaging them in propagation trials becomes a strategic step toward conservation. The study found that suitable habitats for D. engleriana are typically at altitudes between 1500 and 1600 meters, with temperatures not exceeding 15°C during the wettest months. In addition, the results also revealed the negative impact of climate change on habitat suitability, projecting a decrease in suitable areas over the next 50 years. This study addresses a significant knowledge gap and provides valuable insights to guide conservation strategies for D. engleriana.