Search Results (137)

This study aims to provide insights into how physical activity is associated with sleep patterns in youth populations, in particular, Slovak adolescents, and how gender (boys vs. girls) and age (≤16 vs. ≥18) moderate this relationship, using an extreme-group comparison approach that excludes 17-year-olds to enhance contrast between developmental stages. Using a cross-sectional design, self-reported data were collected from 2504 (100%) high school students (aged 15–19; 45.6% boys, 54.4% girls) using the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and the Pittsburgh Sleep Quality Index (PSQI). Participants aged 17 years were excluded from age-stratified analysis to create clearer separation between early/mid and late adolescence. The primary outcome was global sleep quality (PSQI > 5). Secondary outcomes included sleep duration and PSQI component scores. All other analyses (age- and gender-stratified comparisons and interaction models) were predefined as exploratory and hypothesis-generating to examine potential effect modification. Age-stratified analyses among girls showed that, within the low PA group, good sleep was reported by 37.7% of younger girls (≤16) and 28.6% of older girls (≥18). Among older girls, the proportion reporting good sleep increased to 49.8% in the high PA group (χ² = 29.16, p < 0.001). No consistent associations between PA and sleep quality were observed among boys; however, significant association was identified among younger boys (≤16 years), which was not observed in older boys. Logistic regression revealed a modest interaction between age and PA level in predicting sleep quality among girls (β = 0.346, p = 0.049), suggesting small age-dependent variation in the association. This effect should be interpreted cautiously given its borderline statistical significance. Component-level PSQI analyses showed that girls experienced higher rates of sleep disturbances (χ² = 91.40, p < 0.001), longer sleep latency (χ² = 26.71, p < 0.001), and greater daytime dysfunction (χ² = 79.90, p < 0.001). These findings provide region-specific evidence from Central and Eastern Europe and underscore the need for age- and gender-sensitive public health strategies targeting both physical activity promotion and better sleep outcomes, given their observed associations. Full article

Water invasion has become a critical challenge during the late-stage development of gas reservoirs, particularly under harsh conditions characterized by high temperature, high salinity, and strong reservoir heterogeneity. Chemical water shutoff technologies have thus gained increasing attention as effective solutions for selectively restricting water production while preserving gas deliverability. This review systematically summarizes recent advances in chemical water shutoff for gas reservoirs, focusing on polymer gels, nanocomposite materials, relative permeability modification agents, and emerging functional fluids. The reviewed materials are analyzed in terms of dominant sealing mechanisms, gas–water selectivity, reservoir adaptability, and performance under extreme formation conditions. By critically comparing their advantages, limitations, and field applicability, key challenges related to deep placement, selective sealing, long-term stability, and engineering controllability are identified. To address these limitations, emerging concepts such as zonal synergistic water control and bioinspired gas–water barriers are discussed, integrating wettability regulation, multiscale sealing, and adaptive material responses. These strategies provide a conceptual framework and research direction for the design of next-generation, efficient, and sustainable chemical water shutoff systems in complex gas reservoirs. Full article

Prostate cancer is a major cause of cancer-related deaths among men in Sub-Saharan Africa, where late-stage diagnoses are common due to limited access to affordable and sensitive diagnostic tools. Early detection is essential to improve survival and reduce the disease burden. This review explores the integration of epigenetic biomarkers and CRISPR-Cas12a technology as a transformative approach for early, non-invasive prostate cancer detection in resource-limited settings. Among the many complexities of cancer development, molecular dysregulation plays a critical role. Epigenetic modifications including DNA methylation, histone changes, and non-coding RNA expression have emerged as stable and specific biomarkers with significant potential for the early detection and characterisation of prostate carcinogenesis. However, their low concentration in body fluids poses a significant challenge for detection. CRISPR-Cas12a, renowned for its high specificity and sensitivity, offers a promising solution. When integrated with isothermal amplification and liquid biopsy techniques, it enables rapid, point-of-care diagnostics. This review proposes a CRISPR-Cas12a-based diagnostic pipeline for the detection of specific epigenetic markers in liquid biopsies that could be associated with prostate cancer. The adoption of this technology in Sub-Saharan Africa has the potential to significantly improve early diagnosis, reduce mortality, and promote health equity. Full article

Neoproterozoic iron formations (NIFs), deposited during Cryogenian glaciation events, are critical for understanding early Earth oxidation events and the evolution of glacial–interglacial environments. Apatite, a common accessory mineral in iron formations, holds significant implications for sedimentary environments and diagenetic processes, but these aspects remain underexplored. This study focuses on the Hengyang NIF in the Nanhua Basin, South China. Using whole-rock geochemistry and major and trace element analysis of apatite, we investigate the environmental significance of apatite and associated diagenetic processes. Our results show that the Hengyang NIF are formed through the mixing of low-temperature hydrothermal fluids, seawater, and terrigenous detrital materials, with hydrothermal contributions increasing progressively from the bottom to the top of the iron formation layers. Whole-rock geochemical proxies indicate that the depositional water column evolved from relatively oxidizing to weakly oxidizing conditions. The study further demonstrates that the rare earth element patterns in apatite, characterized by middle rare earth element enrichment, are primarily controlled by porewater chemistry during diagenesis. In contrast, Ce anomalies and the V/Cr and V/(V + Ni) ratios in apatite, which are strongly influenced by fluid–rock interactions and magnetite recrystallization, no longer reliably reflect the primary depositional environment. The Th/U ratio in apatite, due to its geochemical stability, aligns with whole-rock trends and serves as a more reliable redox proxy. Based on these findings, we propose a three-stage depositional-diagenetic model: the early and late stages are characterized by high-energy, rapid sedimentation with minimal diagenetic modification, while the middle stage is dominated by low-energy, stagnant conditions with slow sedimentation rates, leading to prolonged diagenesis and significant decoupling of mineral geochemical signatures. This study emphasizes the need to distinguish between sedimentary and diagenetic signals when using mineral geochemical proxies to reconstruct paleoenvironments and provides new insights into the genesis of Neoproterozoic iron formations. Full article

In a previous study, we demonstrated that a novel surface treatment applied to laser-melted Ti6Al4V substrates supports osteoblast-like cell adhesion, proliferation, and the activation of early osteogenic pathways. Building on these preliminary findings, the present work aimed to further investigate the ability of the same surface to promote extracellular matrix (ECM) deposition, organization, and osteogenic maturation, which are critical events for the establishment of a stable bone–implant interface in subperiosteal dental implants. Human osteoblast-like MG-63 cells were cultured on Ti6Al4V discs subjected to different surface treatments, including a proprietary surface modification (ATcs) specifically designed for subperiosteal applications. ECM formation and maturation were evaluated through scanning electron microscopy coupled with energy-dispersive spectroscopy, immunofluorescence, and semiquantitative analyses of osteogenic markers type I collagen (COL1A1), secreted protein acidic and rich in cysteine (SPARC), and dentin matrix protein 1 (DMP1) through Western blotting. The results showed that, while all tested surfaces supported cell adhesion, the ATcs surface promoted a distinct osteogenic profile characterized by enhanced DMP1 expression, organized collagen deposition, and the formation of calcium–phosphate–rich mineralized structures. Compared to surfaces that primarily stimulated cell proliferation or early matrix production, ATcs appeared to favour progression toward late-stage osteogenic maturation and matrix mineralization. Taken together, these findings extend our previous observations and indicate that this novel surface treatment not only supports osteoblast viability and early differentiation but also promotes extracellular matrix maturation, a key prerequisite for effective osseointegration. Although further in vivo studies are required, the present data provide additional biological rationale for the use of ATcs-treated Ti6Al4V surfaces in next-generation custom-made subperiosteal implant designs. Full article

The Jiaodong Peninsula hosts one of the largest gold provinces in the world. The Xincheng gold deposit, located within the Jiaojia gold metallogenic belt, is the largest deposit in this belt and represents a super-large fractured alteration-type gold deposit hosted in fracture zones with relatively well-preserved conditions. Mineralization and hydrothermal alteration are controlled by the Jiaojia Fault zone and its subsidiary faults. The Jiaojia Fault (JJF) serves as the principal ore-hosting structure of the Xincheng deposit, and its multi-stage activity has governed the mineralization, subsequent modification, and preservation of the deposit. However, the post-mineralization cooling, uplift, and exhumation history of the deposit remains poorly constrained. In this study, zircon and apatite fission-track thermochronology analyses were conducted, and inverse thermal history modeling of apatite was performed to reconstruct the tectonic-metallogenic evolution of the Xincheng gold deposit. The zircon fission-track ages range from 90.0 ± 4.0 to 118.0 ± 5.2 Ma, which are younger than the mineralization age (~120 Ma), indicating that the region experienced widespread cooling during the Late Early Cretaceous. This cooling event was likely related to crustal uplift and exhumation triggered by a transformation of the tectonic regime. The apatite fission-track ages range from 15 ± 1.8 to 38 ± 2.7 Ma, recording the Cenozoic cooling and uplift history after mineralization. The inverse thermal history modeling results show that the post-mineralization cooling process can be divided into three stages. The first stage, from 42 ± 5 to 30 ± 4 Ma, is characterized by rapid cooling, with an average cooling rate of 4.23 °C/Myr. The second stage, from 30 ± 4 to 12 Ma, represents a period of slow cooling, with an average cooling rate of 0.98 °C/Myr. Since 12 Ma, the third stage has been marked by renewed rapid cooling, with an average cooling rate of 4.17 °C/Myr. Variations in cooling rates among different stages reflect adjustments in the regional tectonic stress field and the influence of activity along the JJF. Based on the fission track thermochronological data and a reasonable estimate of the geothermal gradient, the total amount of exhumation since 120 Ma is calculated to be approximately 8.22 km. Integration of these results indicates that the shallow portion of the deposit has undergone a certain degree of erosion; however, the overall preservation conditions remain favorable, and significant exploration potential persists at depth and along strike. This study constrains the post-mineralization cooling and erosion history of the Xincheng gold deposit, reveals the controlling role of multi-stage tectonic activity on deposit preservation, and provides new temporal constraints and a scientific basis for preservation assessment and deep exploration of gold deposits in the Jiaodong Peninsula and in regions with similar tectonic settings. Full article

Antimicrobial resistance (AMR) threatens global health, particularly through the rise of multidrug-resistant tuberculosis (MDR-TB) and other critical bacterial infections such as methicillin-resistant Staphylococcus aureus (MRSA). Rifamycins remain frontline antibiotics but are increasingly undermined by resistance. Here, we introduce a click-enabled platform for the synthesis of C8-functionalized rifamycins, which can be converted in a single additional step into efficacious 3′-hydroxy-5′-aminobenzoxazinorifamycins (bxRifs) and enzymatically into 25-deacetylated rifamycins (deAcRifs), providing access to novel antibacterial scaffolds that expand beyond the scope of traditional C8 modifications. Accordingly, we establish a modular strategy for late-stage analog development of the complex natural product rifamycin S, wherein azido and alkyne functionalities are installed via tailored core chemistry and converted into 1,2,3-triazoles through copper(I)-catalyzed click chemistry. Another key feature of this work is the development of systematic HPLC purification methods, enabling the isolation of analytically pure compounds despite structural complexity. The resulting analogs exhibit distinct antibacterial profiles, notably against Gram-positive bacteria including MRSA and Streptococcus mutans, informing structure–activity relationships and offering a foundation for further optimization. This approach supports the rapid diversification of rifamycin scaffolds to combat the escalating threat of AMR, while also establishing a foundation for future discovery through bioorthogonal applications. Full article

Alluvial–proluvial parent-material soils are widely distributed in the Qinghai Lake Basin; however, their timing of development and associated climatic background remain poorly constrained. In this study, two representative alluvial–proluvial fan-covered soil profiles (QRZQ and YXC) from the Qinghai Lake Basin were investigated. Quartz optically stimulated luminescence (OSL) dating was combined with analyses of grain-size composition and soil organic carbon (SOC) to constrain the timing of soil development and its climatic background. The results show that the studied soil profiles are mainly characterized by Ah–As–C and Ah–A–C horizon configurations, with soil development spanning from 15.7 to 1.0 ka. The underlying alluvial–proluvial parent material of the QRZQ profile formed during the Last deglaciation, whereas the oldest OSL ages in the YXC profile occur within a weakly developed A horizon, indicating that this profile had already transitioned from a depositional environment to a pedogenic environment during the Last deglaciation. This contrast reflects staged differences between depositional and pedogenic processes within alluvial–proluvial settings. The soils were formed through upbuilding pedogenesis, in which sediment accumulation and top-down pedogenic modification proceeded concurrently. Grain-size composition and SOC characteristics further indicate that the depositional environment of the YXC profile was relatively stable. Integrating the obtained chronological results with regional climatic changes suggests that climate variability in the Qinghai Lake Basin exerted a primary control on the transformation between sedimentary processes and soil development. In particular, the Late Holocene (0–4 ka), characterized by a generally cold–dry climate accompanied by pronounced humidity fluctuations, represents an important pedogenic stage for alluvial–proluvial parent-material soils in the Qinghai Lake Basin. This study provides a robust chronological framework for further investigating the mechanisms of soil development in alluvial–proluvial environments from a climatic perspective. Full article

The structural characteristics of the Majiatan fault–fold system in the northwestern Ordos Basin are complex, and the detailed 3D distribution of faults and their evolutionary mechanisms remain insufficiently understood, which restricts effective petroleum exploration in this region. To address this, this study utilizes high-resolution 3D seismic data comprising 20 lines (total length 753.371 km, survey grid 3 × 3 km) and drilling and logging data from 13 wells (including synthetic seismograms) to establish a detailed 3D fault model. We aim to elucidate the fault styles and the formation mechanism of the fault–fold–thrust belt. Results indicate the presence of 47 Mesozoic faults, all of which are thrust faults classified into three types. Structural traps dominate the leading transition zone, whereas lithologic–structural traps are prevalent in the Tian-huan Syncline. Laterally, from south to north, the fault occurrence transitions from west-dipping east-thrust to east-dipping west-thrust, accompanied by a shift in tectonic style from thrusting nappe to late-stage reconstruction. The stress intensity generated during the Late Cretaceous increases northward, causing deformation to shift westward. Typical fault styles observed include “y-shaped”, “flower-shaped”, and “imbricated” structures. The middle-north zones of the Majiatan area and the Hengshanbu Thrust Belt share a unified formation mechanism: initiation in the Late Triassic, main development in the Late Jurassic, initial shaping in the Late Cretaceous, and final modification in the Eocene, driven by the rotation of the Ordos Basin and shear tectonic forces. The most favorable exploration zones are identified at the junctions between the leading zone, the fault–fold zone, and weakly transformed zones. The tectonic evolution model established in this study provides a valuable reference for understanding structural complexities and guiding hydrocarbon exploration in similar fold and thrust belts globally. Full article

Noble metal-catalyzed C–H activation has transformed synthetic methodology by enabling direct modification of inert C–H bonds with high levels of efficiency, selectivity, and functional group tolerance. This mini-review provides a focused overview of the mechanistic foundations and emerging advances in C–H functionalization mediated by ruthenium, iridium, rhodium and palladium catalysts. Key activation modes including oxidative addition, concerted metalation deprotonation (CMD), and electrophilic pathways are discussed alongside the roles of high-valent intermediates and ligand control in determining reactivity and regioselectivity. Special emphasis is placed on recent electrochemical strategies, where anodic oxidation replaces traditional chemical oxidants, granting access to unique redox manifolds and expanding the scope of C–C, C–N, C–O, and C–X bond-forming reactions. Representative transformations highlight the versatility of noble metals in constructing heterocycles, enabling enantioselective processes, and facilitating late-stage functionalization of complex molecules. Current challenges and future perspectives are outlined, including the need for improved nondirected activation, deeper mechanistic insight, and enhanced scalability. Collectively, this review underscores the central role of noble metals in advancing sustainable and innovative C–H functionalization chemistry. Full article

This manuscript presents the synthesis of eight novel noracronycine derivatives containing 1,2,4-triazine moiety and evaluates their anticancer activity in vitro. The obtained compounds exhibit activity in the micromolar range and show selectivity towards glioblastoma A172 and breast cancer Hs578T cells. Compounds incorporating a dihydrotriazine moiety demonstrate an enhanced anticancer profile when compared to a noracronycine derivative lacking a triazine substituent. Furthermore, introducing a pyridyl group into the triazine core increases selective cytotoxicity toward cancerous cells. The lead compound exhibits an IC₅₀ value of 3.4 μM for glioblastoma A172, with a selectivity index of 7.59. Mechanistic studies reveal that the obtained compounds slow down cell division, while no significant apoptosis was detected. Full article

The Esquel pallasite provides a valuable record of metal–silicate interaction in differentiated planetesimals, yet many aspects of its formation and thermal evolution remain uncertain. Here, we present a comprehensive multi-technique characterization of a single Esquel specimen, integrating SC-XRD, Raman spectroscopy, SEM–EDS, XPS, magnetic force microscopy, and X-ray computed tomography. Olivine grains are shown to be structurally pristine, with the first full crystallographic refinement for Esquel confirming a single-domain silicate lattice. XPS demonstrates a stoichiometric silicate surface containing only lattice O²⁻, Si⁴⁺, Mg²⁺, and Fe²⁺, indicating that olivine remained chemically unaltered. The Fe–Ni metal preserves diffusion-controlled taenite–kamacite exsolution, compositionally distinct plessite, accessory schreibersite and troilite as resolved by SEM. Quantitative Ni zoning, evaluated through interface-to-center gradients and a width–center-Ni correlation method, yields a self-consistent cooling rate of ~10–20 °C/Myr. MFM reveals microscale magnetic structures that correlate directly with Fe–Ni chemical zoning, providing magnetic confirmation of slow cooling. CT analysis further identifies interconnected metal networks, inclusions, and micro-porosity reflecting melt migration and late-stage modification. These results establish Esquel as an exceptionally well-preserved pallasite and demonstrate the value of integrated, multi-scale analytical workflows for reconstructing early Solar System processes. Full article

Restriction–modification (RM) systems contribute to genome plasticity in Mycoplasma hominis, a facultative pathogen with an extremely small but highly heterogeneous genome. The MhoVII RM system, which contains a fusion of two methyltransferases (MTases), M1 and M2, was recently identified within a family of Type II RM systems, but its specificity and biological function remained unknown. Phylogenetic analysis revealed that M1 and M2 belong to distinct MTase classes clustering within the YhdJ and MTaseD12 branches, respectively. In this study, the dissemination, expression and function of the MhoVII system was analyzed in detail using Oxford Nanopore-based methylation analysis, recombinant expression of the individual RM components in Escherichia coli, and methylation-sensitive restriction assays. It was thus possible to demonstrate that M1 and M2 methylate the complementary non-palindromic motifs GATG and CATC, and that the associated restriction endonuclease cleaves only DNA lacking 6mA methylation at these sites. The transcriptional analysis of mid-to-late logarithmic cultures indicated a polycistronic organization of the MhoVII genes, and GATG/CATC-driven methylation analysis revealed culture-dependent methylation differences, suggesting a post-transcriptional regulation, whereas in the infection of HeLa cells, MhoVII transcription was highest at the beginning and was then gradually downregulated in the later stages of infection. These findings establish MhoVII as a previously uncharacterized Type II RM system. Full article

Background: Maternal aging progressively compromises oocyte competence, yet the precise molecular trajectory across the reproductive lifespan remains insufficiently defined. Methods: Here, we mapped the transcriptomic landscape of mouse germinal vesicle (GV) oocytes across three distinct reproductive stages: post-pubertal peak fertility (Young, 8 weeks), fertility decline (Middle, 12 months), and reproductive senescence (Old, 18 months). Results: Our bioinformatic analyses reveal that oocyte aging follows a biphasic nonlinear trajectory. The transition from Young to Middle age marked the most profound period of transcriptional destabilization, characterized by 1197 DEGs and extensive perturbation of metabolic and signaling networks. To elucidate the regulatory drivers of this early drift, we performed transcription factor binding site (TFBS) analysis, which identified massive regulatory potential involving master regulators such as LHX8, MYC, and GATA4. Interestingly, despite the predicted extensive TF–target interactions, the mRNA expression levels of these TFs remained stable across age groups. This discrepancy suggests that the observed transcriptional dysregulation is likely associated by age-associated epigenetic modifications that alter chromatin accessibility or binding efficiency, rather than TF depletion. In the subsequent transition from Middle to Old age, the landscape shifted from active perturbation to systemic collapse. This late stage was characterized by mitochondrial respiratory dysfunction and severe proteostatic stress. Conclusions: Colectively, our findings define oocyte aging as a biphasic transition from compensatory resistance to systemic collapse. We identify midlife as the critical inflection point of regulatory remodeling, followed by terminal network exhaustion in senescence. This framework provides a molecular foundation for therapeutic and rejuvenation strategies aimed at mitigating age-associated infertility. Full article

Macrocyclic drugs are promising for targeting undruggable proteins, including those in cancer. Our prior work identified BE-43547A₂ (BE) as a selective inhibitor of pancreatic cancer stem cells in PANC-1 cultures, but its high lipophilicity limits clinical application. To address this, we designed derivatives retaining BE’s backbone while modifying tail groups to improve its properties. A concise total synthesis enabled a versatile late-stage intermediate (compound 17), serving as a platform for efficient diversification of BE analogs via modular click chemistry. This approach introduced a central triazole ring connected by flexible alkyl spacers. Key properties, including lipophilicity, solubility, and Caco-2 permeability, were experimentally determined. These derivatives exhibited reduced lipophilicity and improved solubility but unexpectedly lost cellular activity. Direct target engagement studies using MicroScale Thermophoresis (MST) revealed compound-dependent deactivation mechanisms: certain derivatives retained binding to eEF1A1 with only modestly reduced affinity (e.g., compound 29), while others showed no detectable binding (e.g., compound 31). Microsecond-scale molecular dynamics simulations and free-energy calculations showed that, for derivatives retaining target affinity, tail modifications disrupted the delicate balance of drug–membrane and drug–solvent interactions, resulting in substantially higher transmembrane free-energy penalties (>5 kcal/mol) compared to active compounds (<2 kcal/mol). These insights emphasize the need to simultaneously preserve both target engagement and optimal permeability when modifying side chains in cell-permeable macrocyclic peptides, positioning compound 17 as a robust scaffold for future lead optimization. This work furnishes a blueprint for balancing drug-like properties with therapeutic potency in macrocyclic therapeutics. Full article