Search Results (9,728)

The prospects for long-distance space flights are becoming increasingly realistic, and one of the key factors for their implementation is the creation of sustainable systems for producing food on site. Therefore, the aim of our work is to assess the prospects for using millet in biological life support systems and to create predictive models of yield components for automating plant cultivation control. The study found that stress from hypergravity (800 g, 1200 g, 2000 g, and 3000 g) in the early stages of millet germination does not affect seedlings or yield. In a closed system, millet yield reached 0.31 kg/m², the weight of 1000 seeds was 8.61 g, and the yield index was 0.06. The paper describes 40 quantitative traits, including six leaf and trichome traits and nine grain traits from the lower, middle and upper parts of the inflorescence. The compiled predictive regression equations allow predicting the accumulation of biomass in seedlings on the 10th and 20th days of cultivation, as well as the weight of 1000 seeds, the number of productive inflorescences, the total above-ground mass, and the number and weight of grains per plant. These equations open up opportunities for the development of computer vision and high-speed plant phenotyping programs that will allow automatic correction of the plant cultivation process and modeling of the required yield. Predicting biomass yield will also be useful in assessing the load on the waste-free processing system for plant waste at planetary stations. Full article

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that circulates primarily within animal populations and occasionally spills over to humans, causing severe neurological disease. While humans are terminal hosts, veterinary species such as pigs and birds play essential roles in viral amplification and maintenance, making JEV fundamentally a veterinary infectious disease with zoonotic potential. This review summarizes the current understanding of JEV transmission dynamics from a veterinary and ecological perspective, emphasizing the roles of amplifying hosts and animal surveillance in controlling viral circulation. Recent genotype shifts and viral evolution have raised concerns regarding vaccine effectiveness and regional emergence. National surveillance systems and animal-based monitoring strategies are examined for their predictive value in detecting outbreaks early. Veterinary and human vaccination strategies are also reviewed, highlighting the importance of integrated One Health approaches. Advances in modeling and climate-responsive surveillance further underscore the dynamic and evolving landscape of JEV transmission. By managing the infection in animal reservoirs, veterinary interventions form the foundation of sustainable zoonotic disease control. Full article

Background: Langerhans Cell Histiocytosis (LCH) is a rare histiocytic hematological disorder that frequently involves the lungs. Due to a lack of data about sex-related differences in LCH, the aim of this study is to evaluate sex-related differences in pulmonary function in a cohort of patients with LCH. Methods: We retrospectively analyzed data from 79 adult patients diagnosed with LCH. Demographic, clinical, and spirometric data were collected and compared by sex. Continuous variables were analyzed using the Mann–Whitney test and categorical variables were analyzed with the Chi-square test. Results: Out of 79 patients, 47 (59.5%) were females and 32 (40.5%) were males. Women showed significantly lower diffusing capacity of the lungs for carbon monoxide (DLCO%) and lower diffusing capacity of the lungs for carbon monoxide per unit of alveolar volume (DLCO/VA%) compared to men. Females showed a trend toward lower small airway indices, including maximal expiratory flow at 25 (MEF₂₅%) and forced expiratory flow at 25–75% (FEF_25–75%), though this was not statistically significant, while the residual volume-to-total lung capacity (RV/TLC) ratio was significantly higher in women. Among the functional parameters, DLCO% showed the highest accuracy (AUC 0.70) in the identification of lung involvement after multivariate regression analysis. Conclusions: Our findings suggest that the combination of lower gas exchange efficiency and increased peripheral air trapping secondary to small airway involvement in female patients may reflect the presence of a distinct functional LCH phenotype in women characterized by early small airway involvement and altered ventilation–perfusion dynamics, which may influence the clinical management of these patients. Furthermore, the moderate predictive value of DLCO% for lung involvement at baseline in LCH women suggests that DLCO may contribute to the detection of LCH women with lung involvement, although it should not be considered a definitive diagnostic test without a prospective and independent external validation. Full article

Heme, an essential prosthetic group involved in mitochondrial respiration and transcriptional regulation, is synthesized via the rate-limiting enzyme 5-aminolevulinic acid synthase (ALAS). Utilizing heterozygous mouse models for ALAS1 and ALAS2, our studies have revealed diverse systemic consequences of chronic heme deficiency. ALAS1-heterozygous (ALAS1+/−) mice develop metabolic dysfunction characterized by insulin resistance, glucose intolerance, and abnormal glycogen accumulation, linked mechanistically to reduced AMP-activated protein kinase (AMPK) signaling. These mice also exhibit pronounced mitochondrial dysfunction, impaired autophagy, and accelerated aging phenotypes, including sarcopenia and metabolic decline, highlighting heme’s role as a critical metabolic regulator. Additionally, ALAS2 heterozygosity (ALAS2+/−) leads to impaired erythropoiesis, resulting in anemia and ineffective iron utilization. Importantly, supplementation with the heme precursor 5-aminolevulinic acid (5-ALA) significantly mitigates ALAS1+/− phenotypes, restoring metabolic function, mitochondrial health, autophagy, and immune competence. This review encapsulates key findings from our group’s research together with advances made by multiple research groups over the past decade, collectively establishing heme homeostasis as a central regulator of systemic physiology and highlighting the therapeutic potential of 5-ALA in treating heme-deficient pathologies. Full article

Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer entity in Germany, following basal cell carcinoma. Its incidence has increased fourfold over the past three decades. Early diagnosis and treatment are essential for achieving favorable outcomes. Our study aims to identify prognostic factors based on real-world data to improve follow-up protocols and raise clinical vigilance. Methods: We conducted a retrospective, monocenter analysis with a total of 124 patients with at least one cSCC thicker than 3 mm, treated at the Department of Dermatology, University Medical Center Mainz, between 2010 and 2020. Tumor-specific criteria were correlated with patient-specific data, such as gender, age, immunosuppression, UV exposure and mortality. Results: A higher incidence of cSCC was found on UV-exposed skin (91.1%); however, tumors on non-UV-exposed skin were on average thicker (6.55 mm vs. 9.25 mm, p = 0.011) and associated with higher metastasis rates (10.6% vs. 63.3%, p < 0.001). Immunosuppression was strongly associated with a younger age at diagnosis (74 years vs. 81 years), a higher metastasis rate (29% vs. 10.8%, p = 0.021) and a worse 5Y-OS-rate (36.1% vs. 97.8%, p = 0.04). SLNB was performed in eight patients, with one positive SLN identified (12.5%). Local recurrence was observed in 18.1% (n = 21) of patients who did not experience SLNB, whereas no local recurrences (0%) were reported in patients with SLNB (p = 0.349). Discussion: Tumors on non-UV-exposed areas were thicker and more often metastatic, suggesting delayed detection or more aggressive tumor subtypes. Immunosuppression was associated with worse outcomes, underscoring the need for intensified follow-up. SLNB was rarely performed, and larger studies are needed to assess its role. Full article

People with cystic fibrosis may experience polypharmacy, which can increase the risk of drug induced complications such as adverse events and drug–drug interactions. This study aimed to examine the prevalence of adverse events and to identify potential drug–drug interactions associated with elexacaftor/tezacaftor/ivacaftor (ETI). Three databases, the Australian Therapeutic Goods Administration Database of Adverse Event Notification (TGA DAEN), the Canada Vigilance Adverse Reaction Online Database (CVAROD), and the USA Food and Drug Administration Adverse Event Reporting System (FAERS) Database were searched for spontaneous ETI adverse events between 2019 and 2024. Descriptive analysis of the data was undertaken. The FAERS database was analysed to identify adverse events of interest such as anxiety and depression and concomitant drugs prescribed with ETI. A total of 10,628 ETI associated adverse events were identified in all system organ classes. The incidence of psychiatric adverse events ranged from 7 to 15% across the three databases. Potential drug–drug interactions with CYP 3A4/5 strong inhibitors and strong inducers were identified from the FAERS database and azole antifungals were implicated in several ETI dose modifications. The prevalence and types of ETI adverse events were varied and use of concomitant drugs with potential drug interactions was significant, requiring more research to manage them. Full article

The increasing prevalence of chronic metabolic diseases poses a significant challenge in the modern world, impacting healthcare systems and individual life expectancy. The World Health Organization (WHO) recommends that older adults (65+ years) engage in 150–300 min of moderate-intensity or 75–150 min of vigorous-intensity physical activity, alongside muscle-strengthening and balance-training exercises at least twice a week. However, nearly one-third of the adult population (31%) is physically inactive, which increases the risk of developing obesity, type 2 diabetes, cardiovascular diseases, hypertension, and psychological issues. Physical activity in the form of aerobic exercise, resistance training, or a combination of both is effective in preventing and managing these metabolic diseases. In this review, we explored the effects of exercise training, especially on respiratory and pulmonary factors, including oxygen consumption, pulmonary ventilation, and blood gas analyses among adults. During exercise, oxygen consumption can increase up to 15-fold (from a resting rate of ~250 mL/min) to meet heightened metabolic demands, enhancing tidal volume and pulmonary efficiency. During exercise, the increased energy demand of skeletal muscle leads to increases in tidal volume and pulmonary function, while blood gases play a key role in maintaining the pH of the blood. In this review, we explored the influence of age, body composition (BMI and obesity), lifestyle factors (smoking and alcohol use), and comorbidities (diabetes, hypertension, neurodegenerative disorders) in the modulation of these physiological responses. We underscored exercise as a potent non-pharmacological intervention for improving cardiopulmonary health and mitigating the progression of metabolic diseases in aging populations. Full article

Objective: Irritability and reactive aggression are transdiagnostic features that are predictive of adverse long-term outcomes. This investigation examined whether intranasal oxytocin administration impacts the interaction between irritability and reactive aggression, and whether these effects can be detected at a neural level via a facial expression processing task during functional MRI (fMRI). Methods: In this study, 40 children and adolescents with severe irritability and psychiatric diagnoses of disruptive mood and behavioral disorders were assigned to either intranasal oxytocin or placebo administration over a 3-week period in a randomized, double-blind trial (ClinicalTrials, NCT02824627). Clinical measures and fMRI during a facial expression processing task were collected pre- and post-intervention. Brain regions sensitive to oxytocin administration were determined using whole-brain statistical analyses, with post hoc analyses to determine whether changes in the neural activity mediated the relationship between changes in irritability and reactive aggression across the intervention period. Results: Youth who received intranasal oxytocin administration exhibited significant decreases in irritability and reactive aggression compared to their counterparts in the placebo group. Further, oxytocin administration was associated with significant increases in neural activity in the right superior prefrontal cortex, which fully mediated the relationship between improvements in irritability and improvements in reactive aggression. Conclusions: Intranasal oxytocin significantly reduced irritability and reactive aggression in youth, as well as neural activity in the prefrontal cortex, such that increases in the cortical activity fully mediated the relationship between changes in irritability and reactive aggression. Taken together, these findings may reflect oxytocin-related enhancements in emotional regulation in youth with severe irritability, a potential therapeutic mechanism for mitigating reactive aggression. Full article

(1) Background and aim: The benefit of surgical treatment compared to conservative management is unclear in degenerative cuff tears, and there is limited evidence regarding midterm functional outcomes. This study sought to compare the midterm functional outcomes of surgical versus conservative treatment for rotator cuff tears. (2) Methods: All patients on the waiting list for arthroscopy of cuff tears in a single center between 2013 and 2015 were analyzed. They were divided into two groups: those who underwent surgery (arthroscopy group) and those who declined the procedure (orthopedic group). The primary endpoint was shoulder functionality, evaluated with the CMS, SST, and SPADI-SP questionnaires. Inverse probability of treatment weighting (IPTW) was used to account for differences between the groups. (3) Results: Of 57 patients (67 (62–71) years old, 47% women), 32 were in the arthroscopy group and 25 in the orthopedic group. Functionality was assessed at a median of 7 (7–8) years after diagnosis. The patients in the arthroscopy group were younger (p = 0.023) and more frequently women (p = 0.074). No significant differences were observed in the type of tear (p = 0.205) or laterality (p = 0.164). Functional outcome analysis showed more favorable scores in the surgical group: constant (74.5 ± 16.6 vs. 58.4 ± 23, p = 0.016), SST (7.3 ± 3.1 vs. 4.9 ± 4.2, p = 0.016), and SPADI-SP (35.7 ± 26.6 vs. 56.1 ± 30.4, p = 0.006). (4) Conclusions: In this cohort of patients with cuff tears, arthroscopic repair was associated with better clinical and functional midterm results compared to conservative treatment, although the benefit was less evident in older patients and those with complete tears. Full article

Parkinson’s disease (PD) is a progressive, multisystemic α-synucleinopathy, recognized as the second most prevalent neurodegenerative disorder globally. Its neuropathology is characterized by the degeneration of dopaminergic neurons, particularly in the substantia nigra pars compacta (SNpc), and the intraneuronal accumulation of α-synuclein-forming Lewy bodies. Oxidative stress is a key contributor to PD pathogenesis. Thioredoxin-interacting protein (TXNIP) is a crucial regulator of cellular redox balance, inhibiting the antioxidant function of thioredoxin. This pilot study aimed to investigate the protein expression and localization of TXNIP in the SNpc of PD patients compared to healthy controls. We performed immunohistochemical analyses on 12 post-mortem human brain sections (formalin-fixed, paraffin-embedded) from six subjects with PD and six healthy controls. The study was performed on PD subjects with Braak stage 6. Our findings revealed that in control samples, TXNIP protein was distinctly and closely associated with neuromelanin (NM) pigment within the cytoplasm of SNpc dopaminergic neurons. Conversely, in PD samples, there was a markedly weak cytoplasmic expression of TXNIP, and critically, this association with NM pigment was absent. Furthermore, PD samples exhibited a significant reduction in both dopaminergic neurons and NM content, consistent with advanced disease. These findings, which mirror previous transcriptomic data showing TXNIP gene under-expression in the same subjects, suggest that altered TXNIP expression and localization in SNpc dopaminergic neurons are features of late-stage PD, potentially reflecting neuronal dysfunction and loss. Full article

Cardiovascular diseases (CVDs) are the leading global cause of death, with long-term hospitalization becoming increasingly frequent in advanced or chronic cases. In this context, the interplay between systemic factors such as lipid metabolism, circulating metabolites, gut microbiota, and oral health is gaining attention for its potential role in influencing inflammation, cardiometabolic risk, and long-term outcomes. Despite their apparent independence, these domains are increasingly recognized as interconnected and influential in cardiovascular pathophysiology. Methods: This narrative review was conducted by analyzing studies published between 2015 and 2024 from databases including PubMed, Scopus, and Web of Science. Keywords such as “lipid profile,” “metabolomics,” “gut microbiota,” “oral health,” and “cardiovascular disease” were used. Original research, meta-analyses, and reviews relevant to hospitalized cardiac patients were included. A critical integrative approach was applied to highlight cross-domain connections. Results and Discussion: Evidence reveals significant interrelations between altered lipid profiles, gut dysbiosis (including increased TMAO levels), metabolic imbalances, and oral inflammation. Each component contributes to a systemic pro-inflammatory state that worsens cardiovascular prognosis, particularly in long-term hospitalized patients. Despite isolated research in each domain, there is a paucity of studies integrating all four. The need for interdisciplinary diagnostic models and preventive strategies is emphasized, especially in populations with frailty or immobilization. Conclusions: Monitoring lipid metabolism, metabolomic shifts, gut microbial balance, and oral status should be considered part of comprehensive cardiovascular care. Gut microbiota exerts a dual role in cardiac health: when balanced, it supports anti-inflammatory and metabolic homeostasis; when dysbiotic, it contributes to systemic inflammation and worsened cardiac outcomes. Future research should aim to develop integrative screening tools and personalized interventions that address the multifactorial burden of disease. A systemic approach may improve both short- and long-term outcomes in this complex and vulnerable patient population. Full article

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Acute kidney injury (AKI) is a serious clinical condition that is linked to markedly higher rates of morbidity and mortality in cirrhosis patients. Its diagnosis is challenging due to overlapping clinical and laboratory features among causes such as hepatorenal syndrome (HRS), acute tubular injury (ATI), and prerenal hypovolemia. In order to address the distinct pathophysiology and clinical context of cirrhosis, the definitions and classification of AKI have changed over time, moving from RIFLE and AKIN to KDIGO and ICA-AKI. Because cirrhosis patients have altered muscle mass and fluid retention, traditional markers like serum creatinine (sCr) and urine output have significant limitations. Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C (CysC) are some of the new biomarkers that have shown promise in early AKI detection and in differentiating structural from functional kidney injury. NGAL and KIM-1 are sensitive indicators of tubular damage with potential prognostic implications. IL-18 reflects inflammatory injury, and CysC offers a more reliable measure of glomerular filtration. Incorporating these markers may improve early diagnosis, risk stratification, and treatment decisions, representing a key direction for future research in managing AKI in cirrhosis. Full article

Arginine kinase is a key phosphagen kinase in invertebrates that facilitates rapid ATP regeneration by reversibly transferring phosphate groups between phosphoarginine and ADP. Structural studies have shown that the enzyme adopts distinct conformations in its ligand-free and ligand-bound states, known as the “open” and “closed” forms, respectively. These conformational changes are crucial for catalytic activity, enabling precise positioning of active-site residues and loop closure during phosphoryl transfer. Transition-state analog complexes have provided additional insights by mimicking intermediate states of catalysis, supporting the functional relevance of the open/closed structural model. Furthermore, studies across multiple species reveal how monomeric and dimeric forms of arginine kinase contribute to its allosteric regulation and substrate specificity. Beyond its metabolic role, arginine kinase is also recognized as a major allergen in crustaceans. Its structural uniqueness and absence in vertebrates make it a promising candidate for selective drug targeting. By integrating crystallographic data with functional context, this review highlights conserved features and species-specific variations of arginine kinase that may inform the design of inhibitors. Such molecules have the potential to serve both as antiparasitic agents and as novel therapeutics to manage crustacean-related allergic responses in humans. Full article

Caffeine is a widely consumed psychoactive compound known to influence drug metabolism and efficacy through interactions with key enzymes such as cytochrome P450 3A4 (CYP3A4). This study investigates the molecular impact of caffeine on the binding behavior of imatinib, a first-line BCR-ABL tyrosine kinase inhibitor, using molecular docking simulations. Structural optimization and lipophilicity analyses were conducted using HyperChem, while docking was performed with HEX software (Version 8.0.0) against the CYP3A4 receptor (PDB ID: 1W0E). Two administration scenarios were evaluated: concurrent caffeine–imatinib complex formation and sequential administration with caffeine pre-bound to CYP3A4. The caffeine–imatinib complex exhibited a predicted increase in lipophilicity (logP = 3.09) compared to imatinib alone (logP = −1.29), which may indicate the potential for enhanced membrane permeability and tissue distribution. Docking simulations revealed stronger binding affinity of the complex to CYP3A4 (−350.53 kcal/mol) compared to individual compounds, and improved imatinib binding when CYP3A4 was pre-complexed with caffeine (−294.14 kcal/mol vs. −288.19 kcal/mol). Frontier molecular orbital analysis indicated increased reactivity of the complex (ΔE = 7.74 eV), supporting the hypothesis of altered pharmacodynamic behavior. These findings suggest that caffeine may modulate imatinib’s metabolic profile and therapeutic efficacy by enhancing receptor binding and altering drug distribution. The study underscores the importance of evaluating dietary components during drug development and therapeutic planning, particularly for agents metabolized by CYP3A4. Full article