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Potential medical applicability of N-β-Ala and N-His dipeptidomimetics against breast cancer: short in vitro and in silico screening
Abstract Short peptides conjugated to drugs are found to effectively improve wellbeing and recovery of cancer patients. However, to combat poor stability and bioavailability, their polar groups can be protected to form mimetics. Therefore, here we present synthesis, short biological screening and detailed computational analysis of 18 N -terminal β-alanine and L-histidine dipeptidomimetics, to estimate their preliminary relevance as cancer therapeutics intermediates for conjugation. While extended biological experiments are deeply relevant to define drug functionality, they also require extensive financial resources. Herein, we employed computational methods to better estimate possible activities of the compounds, and create a perspective between in silico and in vitro to hypothesize on the acquired results. Most efficient representatives of each group were β-Ala-Ala (BAA) and His(Bn)-Val (HV) dipeptidomimetics, which seem to show signs of selectivity. Our research provides detailed theoretical data for scientists searching for their new conjugative agents to study. We hope to encourage other experts to incorporate computational methods into their research, to increase clarity and available data for further research.
Exploring dysregulation of cuproptosis-related genes molecular clusters and candidate biomarkers in pterygium
3D printed hydrogel scaffold incorporating keratin and melatonin-loaded nanomicelles for cartilage tissue engineering
Multi-objective scheduling optimization for linear megaprojects considering technological innovation
Comparative evaluation of four reference genes for qRT-PCR assays in snow trout (Schizothorax richardsonii) under multiple experimental conditions
Effect of intrasphincteric botulinum toxin on postoperative urinary retention following stapled hemorrhoidopexy: a randomized, double-blind, placebo-controlled trial
Evaluation of regression, reactivation, retreatment and retinal detachment after injections of three different anti-VEGF drugs for retinopathy of prematurity
Condom use and associated factors among people living with HIV/AIDS on Anti-Retroviral Therapy (ART) in Ethiopia: a systematic review and meta-analysis
The relationship between objective and subjective cognitive performance and clinical and MRI disease burden in early multiple sclerosis
Abstract Subjective cognitive performance in multiple sclerosis (MS) correlates weakly with objective performance, but is more strongly associated with depression. We aimed to identify symptoms and brain MRI volumes related to subjective and objective cognitive performance. 205 MS subjects, diagnosed within the last 15 years, completed the SymptoMScreen, patient-reported Expanded Disability Status Scale, Neuro-QoL subjective cognitive and fatigue sub-scores, and Beck Depression Inventory. For the objective cognitive assessment the smartphone-based icompanion Symbol test was used. Volumetric variables were calculated from the 52 available brain MRIs using icobrain. A weak correlation was observed between subjective and objective performance (rho = 0.21, p = 0.002). Subjective performance was negatively associated with pain, dizziness, fatigue and depression, while objective performance was negatively related to walking impairment. Objective performance significantly correlated with thalamic volume, while subjective performance did not correlate with any brain volumes. In other words, subjective and objective cognitive performance are related to different clinical markers: subjective performance is linked to invisible symptoms, while objective performance is linked to more visible measurable clinical markers. Integrating both perspectives in clinical practice may provide a more holistic understanding of cognition in MS, allowing for tailored interventions that enhance patient care and quality of life.
H3K9me3 controls epidermis morphogenesis by regulating RNA Pol II dynamics at developmental promoters and enhancers
Abstract Histone H3K9me3 silences repetitive elements and represses non-lineage genes during early development, but its role in organogenesis is understudied. Here, we show that H3K9me3 deposition is dynamic during epidermis morphogenesis and essential for lineage diversification. We ablate Suv39h1, Suv39h2, and Setdb1 histone methyltransferases, in the embryonic mouse epidermis, to induce H3K9me3 loss. This causes complete failure of keratinocyte differentiation, skin barrier formation, hair follicle development, and Merkel cell specification. Single-cell transcriptomics reveals aberrant cell fates with mixed epidermal subtype identities and dysregulated non-lineage and lineage-specific transcription programs. Affected pathways include differentiation, metabolism, cell cycle, cytoskeletal organization, and extracellular matrix. H3K9me3 primarily restricts RNA Pol II transcription initiation at key developmental promoters and enhancers and has minimal direct effect on promoter-proximal pause release. We uncover a cooperative and indispensable role for Suv39h1, Suv39h2, and Setdb1 in gene expression control of epidermal morphogenesis, establishing H3K9me3 as a critical developmental determinant of skin organogenesis.
Self-grown mycelium in confined geometries as nanofluidic devices
Abstract Precise control of ion and molecular transport at the nanoscale underpins next-generation nanofluidic technologies. However, current approaches such as top-down fabrication and bottom-up assembly remain constrained by cost, scalability, or limited programmability. Fungal mycelium—the largest natural ion transport network in soil—offers a living bio-derived route to nanofluidics. Here, we harness mycelium’s self-growth and hyphal anastomosis to construct nanofluidic structures that autonomously conform to confined geometries. With interconnected fibrous networks, nanoscale porosity, and negatively charged surfaces (−2.8 to −4.1 mC m −2 ), multispecies mycelium generates in situ adaptive pathways through channels, gaps, and open volumes. Specifically, a mycelium-integrated microchannel achieves a pH-gating switch ratio of up to 3.0 and a 55-fold enrichment for dilute cation detection. These results establish the principle that nanofluidic functionality can be biologically grown rather than fabricated, introducing a scalable, sustainable, and geometrically adaptable platform. By bypassing lithography and energy-intensive processing, this bio-derived strategy may enable living and self-organizing ion transport networks with potential applications in sensing, ionic computing, and energy conversion.
α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron–microglia communication
Abstract Tunneling nanotubes (TNTs) enable direct intercellular transfer of macromolecules, organelles, and pathogenic protein aggregates. While α -synuclein ( α -Syn) aggregates are known to promote TNT formation, the underlying mechanisms remain poorly defined. Here, using human neuronal and microglial cell lines, as well as iPSC-derived dopaminergic neurons and microglia, we show that α -Syn aggregates induce severe mitochondrial damage, leading to cytosolic release of mitochondrial DNA (mtDNA) and activation of the cGAS–STING–NF-κB–IRF3 pathway. This innate immune response drives actin cytoskeleton remodeling and the formation of TNT-like structures, promoting intercellular transfer of α -Syn from neurons to microglia. Additionally, neuronal cells transfer damaged mitochondria to microglia, where they undergo lysosome-mediated degradation. Neuron-to-microglia communication under α -Syn-induced stress also triggers a bystander inflammatory response in microglia, suggesting a neuroimmune activation. Our findings identify mitochondrial damage and STING-mediated inflammation as key drivers of TNT formation and α -Syn propagation, highlighting potential targets to modulate disease progression in Synucleinopathies.
Jets from a stellar-mass black hole are as relativistic as those from supermassive black holes
Organic-inorganic hybrid scintillating glass for high-energy particle detection
Mapping the spatiotemporal continuum of structural connectivity development across the human connectome in youth
Abstract Childhood and adolescence are marked by protracted developmental remodeling of cortico-cortical structural connectivity. However, the spatiotemporal variability of white matter connectivity development across the human connectome and its relevance to cognition and psychopathology remains unclear. Using diffusion MRI data from three independent developmental cohorts spanning youth, we identified a robust divergence in structural connectivity maturation along a predefined sensorimotor-association (S-A) connectional axis during youth ( http://connectcharts.cibr.ac.cn ). This developmental continuum ranged from early childhood increases in sensorimotor-sensorimotor connectivity strength to late adolescent increases in association-association connectivity strength, with the transition occurring around age 15. The S-A connectional axis also captured spatial variations in the associations between structural connectivity and both higher-order cognition and general psychopathology. Moreover, group-level developmental trajectories of structural connectivity differed by cognitive and psychopathological levels, with psychopathological effects predominantly observed in association connections. These findings delineate a spatiotemporal continuum of structural connectivity development during youth, providing a normative reference for quantifying developmental variability in psychiatric disorders.
LTBP4 deficiency inhibits NLRP3 inflammasome activation in cardiomyocytes and attenuates heart failure in male mice
Association between hemoglobin glycation index and cognitive function: Evidence in the elderly
Background Cognitive impairment has been a major public health challenge. This study aims to estimate the association of hemoglobin glycation index (HGI) with cognitive function in U.S. older adults. Methods In this cross-sectional study, data from the National Health and Nutrition Examination Survey (NHANES, 2011–2014) was obtained. Cognitive function was assessed based on the three scales [Digit Symbol Substitution Test (DSST), Animal Fluency Test (AFT), and Consortium to Establish a Registry for Alzheimer’s disease (CERAD)], along with a composite Z-score derived from the sum of the Z-scores of these three assessments. We used weighted univariate and multivariate linear regression to estimate the unstandardized β coefficient and 95% confidence interval (CI) of the association between HGI levels and cognitive function. Results Our study comprised a total of 1,406 subjects. As compared with the second tertile of HGI, the lowest tertile had a lower Z-score [β = −0.13 (95% CI: −0.25, −0.01)] and CERAD score [β = −1.07 (95% CI: −1.93, −0.21)] in the fully adjusted model. For the highest tertiles of HGI ( vs. second tertile), Z-score and DSST decreased by 0.16 (95%CI: −0.31, −0.01) and 3.09 (95%CI: −6.00, −0.18), respectively. Females in the lowest HGI tertile ( vs. second HGI tertile) exhibited a decline in cognitive function scores (Z-score, CERAD, AFT; all P < 0.05), while males in the highest tertile of HGI ( vs. second HGI tertile) showed decreased cognitive function scores (Z-score, DSST; all P < 0.05). In addition, Z-score and CERAD scores also decreased (all P < 0.05) in the highest HGI tertile ( vs. second HGI tertile) among non-users of antidiabetic drugs. Conclusion Both lower and higher HGI levels are associated with cognitive decline. Lower HGI is related to poorer learning and memory, while higher HGI is associated with executive function impairment. Future longitudinal studies are need to verify whether changes in HGI levels can be used as an early warning indicator for cognitive decline.
Divergence among species with “good competitor” and “good cultivator” strategies promotes asymmetric facilitation among co-invaders
Vaccine confidence and hesitancy among mothers of children under six years of age in Salvador, Brazil: The role of sociodemographic factors and health service experience
Background Vaccine hesitancy remains a pressing global health concern, particularly in early childhood, where delays or refusal to vaccinate can significantly compromise public health. Despite the recognized benefits of immunization, concerns about vaccine safety, efficacy, and necessity persist among some parents. We aimed to analyze vaccine hesitancy among mothers of children under six years old in Salvador, Bahia, Brazil. Method A cross-sectional study was conducted in 2023 involving 503 mothers of children under six registered at Family Health Units in Salvador. Data were collected through structured interviews assessing socioeconomic and health characteristics, vaccination status, and attitudes toward vaccines using a standardized questionnaire. Descriptive statistics and chi-square tests were used, with a significant level of 5%. Results Most mothers acknowledged the importance of vaccination, and over 80% expressed trust in vaccines; however, 27% demonstrated some degree of vaccine hesitancy. Higher maternal education (more than 11 years) was associated with greater vaccine confidence (β = −0.156, p = 0.002). In contrast, negative or neutral relationships with primary health care professionals were linked to lower trust and higher perceived vaccine risks (β = 0.123, p = 0.038). Mothers who declined new vaccines also showed significantly lower confidence in vaccination (β = 1.057, p = 0.002). Conclusions Although vaccine confidence is generally high, a substantial proportion of mothers still exhibit hesitancy—often influenced by educational level, healthcare relationships, and trust in newer vaccines. These findings highlight the need for targeted strategies that strengthen provider–parent relationships and build trust in vaccine safety to reduce hesitancy and protect child health.