Search Results (489)

Background and Objectives: Pelvic ring injuries with symphyseal disruption are classically associated with high-energy mechanisms such as motor vehicle collisions. Recently, waterslides have emerged as an underrecognized but distinct source of severe pelvic trauma. Waterslide-related pelvic trauma represents a distinct biomechanical entity characterized by a supine or semi-supine body position at splashdown, extreme forced hip abduction, asymmetric lower-limb positioning, and abrupt hydrodynamic deceleration. The high descent velocity, abrupt hydrodynamic deceleration, and forced hip abduction at water entry may combine to generate open-book-type pelvic injuries. Evidence guiding diagnosis and surgical management in this setting remains scarce. Materials and Methods: We retrospectively analyzed a consecutive series of adult patients sustaining waterslide-related anterior–posterior compression type II (APC2) pelvic ring injuries. Demographic data and the body mass index (BMI), fracture classification, surgical strategy, complications, and functional outcomes were reviewed. Only patients with complete imaging, operative records, and follow-up were included. Results: Four patients (38–72 years) met the inclusion criteria. All sustained rotationally unstable open-book pelvic injuries and were classified as APC2; three were AO/OTA 61B2.3 and one 61B3.3. All patients were overweight or obese (BMI 27.2–31.2). Pelvic binders provided an effective acute reduction in symphyseal diastasis; however, in one bilateral injury, CT imaging obtained with the binder in situ masked posterior ligamentous instability. Definitive surgical fixation was performed in all cases. Early mechanical failure occurred in two patients treated with short anterior symphyseal plate constructs. In the bilateral injury, isolated anterior fixation failed repeatedly until posterior sacroiliac stabilization was added. No deep infections or thromboembolic events occurred. Although two patients required short observational ICU stays, none were admitted for hemodynamic instability or pelvic bleeding. Conclusions: At 12-month follow-up, three patients achieved pain-free ambulation without assistive devices, while one patient required intermittent use of a single crutch; all patients regained independence in daily activities. Waterslide accidents represent a high-energy injury mechanism capable of producing severe APC2 pelvic disruptions, particularly in patients with an elevated BMI. Awareness of this mechanism and meticulous assessment of posterior stability are essential to avoid under-treatment and mechanical failure. Full article

PET biodegradation remains limited due to its intrinsic properties—high crystallinity, hydrophobicity, and strong chemical stability. These characteristics lead to extremely slow degradation rates and contribute to PET’s persistence in the environment. Understanding how microorganisms respond at the molecular level when exposed to such a recalcitrant polymer is therefore essential. Living organisms express genes in response to their needs during development. When microbes are under critical conditions, such as when contaminants are present, they express genes encoding specific enzymes that attack the pollutant. In this study, a fungus isolated from the infected fruit of the plant Randia monantha was identified as Aspergillus terreus. It was tested for polyethylene terephthalate (PET) degradation, and the fungus Aspergillus nidulans was evaluated due to its previously reported recombinant cutinases for PET degradation. A microplastic polyethylene terephthalate (PET-MP) particle size of <355 μm for degradation was established, and a PET weight loss of 1.62% for A. nidulans and 1.01% for A. terreus was found. Additionally, the degradation of PET was confirmed by FTIR and SEM. This study also compares the transcriptomic profiles of Aspergillus nidulans and Aspergillus terreus during cultivation with PET-MP residues, which serve as a replacement for the carbon source. We present the first evidence of chitinase overexpression during direct exposure of PET to Aspergillus fungi. Interestingly, chitinase expression was detected in the crude extracts of A. nidulans and A. terreus during culture in the presence of PET residues, which replaced the carbon source. The chitinase produced by each fungus has a similar molecular weight of approximately 44 kDa. Chitinase activity was monitored over a 14-day cultivation period; from day 2, chitinase activity was detected in both cultures and continued to increase until day 14, when the highest values reported in this work were 24.88 ± 4.17 U mg⁻¹ and 10.41 ± 0.47 U mg⁻¹ for A. nidulans and A. terreus, respectively. Finally, we proposed a pathway for PET degradation by Aspergillus fungi that involves mycelial adherence and the secretion of hydrophobins, followed by the production of intermediates and monomers via esterase hydrolysis, and ultimately, the entry of monomers to the ethylene glycol (EG) and terephthalic acid (TPA) pathways, further suggesting these Aspergillus as candidates to produce valuable compounds under these conditions, such as muconic acid, gallic acid, and vanillic acid. Full article

The MERS-CoV (Middle East respiratory syndrome coronavirus) is a zoonotic virus with a high mortality rate and a lack of antiviral drugs, underscoring the need for effective therapeutic methods. Viral entry depends on interactions between viral surface proteins and human receptors, with Dipeptidyl Peptidase-4 (DPP4), a transmembrane glycoprotein, acting as the receptor for MERS-CoV. We employed Molecular Dynamics (MD) Simulations to identify critical interface residues under a high-performance computing (HPC) workflow for accelerated results. Target residue pairs were identified through analysis of salt bridge and hydrogen bond occupancy. The stability of these residues was confirmed through three independent MD Simulations at human body temperature and constant pressure. Additionally, binding affinity predictions were calculated to determine the interaction strength between the virus and human receptors. Applying the scientific threshold criteria, we narrowed our results to seven key interaction pairs; two of the identified pairs (Asp510-Arg317, and Arg511-Asp393) are consistent with findings published in previous research studies, and five novel interactions are proposed for future experimental studies with our active collaborators in Pharmacology. The results provide a molecular basis for targeted mutation-based experiments and support the rational design of structure-based inhibitors aimed at disrupting the MERS-CoV-DPP4 complex, thereby facilitating the translation of computational findings into antiviral drug discovery. Full article

The early identification of patients with highly active multiple sclerosis (HAMS) is crucial for guiding therapeutic decisions and initiating high-efficacy treatment strategies. This study aimed to characterize peripheral immune profiles that can distinguish between patients who are candidates for intensive therapy at disease onset and in later stages. Using spectral flow cytometry, we identified distinct immune signatures to differentiate early-stage patients from those with refractory, long-standing disease. In newly diagnosed individuals, decreased herpesvirus entry mediator (HVEM) expression on effector T helper (Th) cells distinguished HAMS from non HAMS cases. In contrast, patients with therapeutic resistance exhibited reduced CD28 expression on naïve regulatory and CD8⁺ T cells. Disability progression was associated with elevated HVEM on classical monocytes, decreased CD70 on CD56^bright natural killer cells (NK), and lower programmed cell death protein 1 (PD-1) expression on memory Th cells. Notably, CD28 expression on terminal effector CD8⁺ T cells and HVEM levels on plasmablasts emerged as strong predictors of progression independent of relapse activity, while higher PD-1 memory Th cell frequencies predicted clinical stability. This study identifies two panels of immune biomarkers: one distinguishing candidates for early high-efficacy intervention, and another defining patients with refractory disease. The immunological landscape of HAMS evolves across disease stages. In addition, we defined progression-associated markers detectable at the outset of follow-up, enabling the timely recognition of patients at heightened risk of disability accumulation, discriminating between neurodegeneration-driven and inflammation-driven mechanisms of progression. Full article

Circular RNA (circRNA) has emerged as a promising vector for drug delivery because, unlike linear mRNA, it does not require costly chemical modifications and offers greater stability and sustained expression in cells. Lacking the canonical 5′ cap structure, circRNA relies primarily on internal ribosome entry sites (IRES) to initiate translation, but IRES-mediated initiation is less efficient than cap-dependent translation. To overcome this limitation, we devised a dual-IRES strategy that introduces a second IRES to drive translation of the coding sequence (CDS). By testing several IRES elements known for high translational activity, this study shows that IRESs derived from the EMCV (Encephalomyocarditis virus) family can enhance expression when placed at the 3′ of the CDS, in coordination with the 5′ EMCV-derived IRES. The optimal dual-IRES combinations identified in this study display compatibility with two different coding sequences, offering a useful strategy to enhance circRNA translation. Full article

Background/Objectives: Antisense oligonucleotides (ASOs) hold great therapeutic potential due to their precise ability to modulate gene expression, particularly for treating genetic and neurological disorders. However, effective delivery of ASOs remains a major challenge. While most recent research focused on lipid nanoparticles (LNPs) as ASO carriers, alternative formulations, preparation methods and lipid compositions on delivery optimization are not fully explored. In this study, we investigated two types of formulations, lipoplexes (LPXes) and LNPs, prepared using lysine-type cationic lipids, K3C14 or K3C16, selected from a lysine-type lipid mini-library for their superior formulation stability and distinct cellular entry mechanisms. Methods: The physicochemical properties of the formulations were characterized using dynamic light scattering. Cytotoxicity was evaluated in spleen and liver cell lines. LPXes and LNPs were assessed for ASO delivery efficiency using an engineered HEK293 split-luciferase cell line, while immune response was evaluated in human peripheral blood mononuclear cells. Cryogenic electron microscopy (Cryo-EM) images were captured for structural analysis. Results: Lysine-type lipid mini-library screening identified lipids with either a hydrocarbon spacer K3 or C14 fatty acid tail exhibiting great stability and safety. Among the tested LPX and LNP formulations, the K3C16 lipoplex demonstrated ASO delivery efficiency and immune responses comparable to the benchmark SpikeVax LNP formulation. Notably, Cryo-EM imaging revealed novel structures that have not been reported previously; the K3C14 lipoplex formed a rouleaux-like structure, whereas the K3C16 lipoplex exhibited a lipid nanosheet-like structure, distinct from the conventional LNP structure. Conclusions: These results highlight the potential of an unconventional type of lipid assembly for efficient ASO delivery. Full article

The career anchor (CA) is a metaphor created by Edgar Schein to illustrate the role of patterns of self-perceived talents, motives, and values in guiding, stabilizing (i.e., anchoring), and integrating a person’s work career. With the early years of work experience, this pattern tends to stabilize into one of the possible CAs and plays two main roles: guiding the selection of specific occupations and work environments; shaping individual reactions to the actual occupation and work environment. Since Schein’s initial conceptualization, theoretical refinements have been proposed, suggesting that CAs can change over time and that multiple CAs can coexist. Although substantial evidence supports the theory’s key predictions, the available literature appears fragmented, with a primary focus on descriptive concerns. Actual measurement issues also limit the development of theoretical knowledge. This entry provides an updated overview of the central predictions related to CAs, aiming at promoting greater integration and coherence in research and practice. Full article

Accumulating evidence recognizes cardiovascular–kidney–metabolic syndrome (CKMS) as a life-course disorder arising from dynamic and maladaptive interactions among the heart, vasculature, kidneys, liver, and pancreas. Beyond a late-onset clinical entity, CKMS susceptibility is increasingly understood to be programmed during critical developmental periods. Redox imbalance has emerged as a central integrative mechanism in this process, functioning as a mechanistic interface through which adverse early-life environments translate into persistent multi-organ vulnerability. Perturbation of the reactive oxygen species–nitric oxide axis during development disrupts organogenesis, vascular maturation, and metabolic regulation, resulting in enduring structural and functional alterations that predispose individuals to hypertension, metabolic dysfunction, and chronic kidney disease. These insights position redox biology not merely as a pathogenic mechanism but as a strategic entry point for precision intervention. Addressing the escalating global burden of CKMS requires a paradigm shift toward redox-driven precision medicine. This framework integrates biologically informed phenotyping, life-course–based risk stratification, early precision prevention through developmental reprogramming, and phenotype-guided therapeutics to stabilize interconnected organ networks. Transitioning from reactive, fragmented care to a proactive, systems-oriented approach offers a transformative opportunity to interrupt intergenerational risk transmission and achieve durable improvements in cardiovascular–kidney–metabolic health across the lifespan. Full article

To address the insufficient bearing capacity and severe deformation of narrow coal pillars in deep gob-side entries under the influence of residual dynamic loading and hydraulic punching of the coal mass, this study investigates the plastic-damage evolution mechanism of narrow pillars and proposes a novel “grip-anchoring (GA)” collaborative support system. A physical model testing system for narrow coal pillars reinforced by double-pull cable bolts was established based on similarity theory, and six support schemes were designed for comparative experiments. Digital image correlation was employed to analyze the displacement field and the evolution of plastic failure, and an industrial-scale field test was carried out to verify the reliability of the proposed support technology. The results indicate that the double-pull cable bolts, through a “dual-tensioning and synergistic locking” procedure, can effectively solve the support challenges of narrow coal pillars under asynchronous excavation. The dense double-row double-pull cable-bolt scheme maintained overall structural stability even under a 2.5p overload, with only localized damage occurring at the roof- and floor-corner zones of the pillar. This scheme exhibited the smallest deformation and the highest peak load among all tested configurations, demonstrating its significant advantage in enhancing structural stability. Full article

Flexible-formwork concrete (FFC) is widely adopted in gob-side entry retaining (GER). However, the roadside FFC wall cannot provide sufficient load-bearing capacity immediately after casting. This time-dependent strength gain induces a distinct structural and mechanical asymmetry—solid coal on one side versus a developing FFC wall on the other—which significantly amplifies advance-pressure-driven roof damage. Field inspections using borehole cameras in the N1215 panel of the Ningtiaota Coal Mine confirmed this failure mechanism, revealing severe roof fracturing and progressive degradation in the advance zone. To address this, a three-dimensional numerical model was established to reproduce the full mining process and identify the pressure zoning characteristics. Parametric comparative simulations were systematically performed considering three key design variables: advance support length, hydraulic prop spacing, and roof anchor cable spacing. To strictly quantify the control performance, a comprehensive evaluation system was defined, including roof stress increase rate, side abutment pressure increase rate, and deformation control rate. The results indicate that the advance-pressure-affected region extends significantly ahead of the face, and the marginal benefit of support intensification diminishes beyond specific thresholds. Consequently, a symmetry-enhancing “hydraulic prop-anchor cable coupled” advance support strategy was proposed to compensate for the inherent asymmetry of FFC-based GER. Field application in the belt transport roadway of the N1215 panel indicates that roadway convergence was effectively restrained, with roof–floor convergence of 13 mm and side convergence of 9 mm at the monitored section, confirming the applicability of the optimized design for maintaining entry stability during safe mining. Full article

High-water material (HWM) is widely used for roadside filling in gob-side entry retaining (GER), where its creep behavior under sustained loading critically influences the long-term stability of the roadway. To enhance the long-term mechanical performance of HWM, this study modified it with polyethylene (PE) fiber and conducted uniaxial compression creep tests to investigate the effects of fiber content on time-dependent deformation, long-term strength, and failure time. The results indicate that when the applied stress remains below the long-term strength, the creep deformation of PE fiber-modified HWM stabilizes over time. In contrast, under higher stress levels, the deformation of HWM continuously develops over time and progresses through three stages: attenuation, steady-state, and accelerated creep, ultimately resulting in failure. Compared with pure HWM, the fiber-modified material exhibits a significant improvement in long-term strength, which increases linearly with fiber content. Furthermore, a higher fiber content raises the stress threshold for creep failure and substantially extends the time to failure. To predict the creep response of PE fiber-modified HWM, a viscoelastic-plastic creep damage model was developed using the component combination method, incorporating the Riemann–Liouville fractional-order integral operator and a time-dependent damage evolution equation. The reliability of the model was verified by utilizing the experimental data, and a sensitivity analysis of the model parameters was carried out based on the fitting results. The proposed model can not only describe the creep behavior of HWM across all loading stages, including the accelerated creep phase, but also accounts for the effect of fiber content on long-term strength. These findings can provide a theoretical foundation for the design and stability assessment of fiber-reinforced HWM roadside backfills in GER engineering. Full article

To address the instability of small coal pillars in gob-side entry driving under thick and hard roof conditions, this study proposes a synergistic control technology combining “pressure relief, bundle control, and strong support”. First, a segmented deflection curve model of the coal pillar was established to quantify the correlation between pillar deformation and dominant controlling factors. Numerical simulations (FLAC3D) were then performed to optimize the roof cutting parameters, determining an optimal cutting height of 23.2 m and a cutting angle of 9°. Based on these findings, a comprehensive control scheme was implemented in the Fucun Coal Mine. Field monitoring results indicate that the proposed technology effectively controlled the lateral displacement of the coal pillar to 264 mm and maintained the stability of the roadway. This study provides a theoretical basis and practical reference for deformation control in similar geological conditions. Full article

Quiescence is a reversible, non-proliferative cellular state that enables survival under nutrient limitation while preserving the capacity to resume growth. Rather than representing a passive default, quiescence is an actively regulated program conserved from unicellular eukaryotes to metazoans. This review focuses on the nuclear mechanisms underlying quiescence entry, maintenance, and exit, with primary emphasis on mechanistic insights from yeast models while highlighting conserved principles in multicellular systems. Across species, quiescence is characterized by global transcriptional repression, chromatin compaction, and the extensive reorganization of nuclear architecture, coordinated by nutrient-sensing pathways centered on TOR/mTOR signaling. We discuss how transcriptional reprogramming is achieved through redistribution of RNA polymerases, dynamic transcription factor activities, and large-scale remodeling of histone modifications, alongside repressive chromatin formation. In parallel, post-transcriptional mechanisms—including intron retention, alternative polyadenylation, and accumulation of non-coding RNAs—fine-tune gene expression while limiting biosynthetic output. We further examine how changes in nuclear organization, such as nucleolar condensation, condensin-mediated chromosome rearrangements, and telomere hyperclusters, support long-term viability and genome stability. Collectively, this review highlights nuclear dynamics as an integrative regulatory layer that links metabolic state to cellular identity, adaptability, and long-term survival, with broad implications for development, stem cell function, and disease. Full article

Slag entrainment within the mold is a significant cause of surface defects in continuously cast slabs. As a key component for controlling molten steel flow, the structure of the submerged entry nozzle directly influences the flow field characteristics and slag entrainment behavior within the mold. This paper employs a 1:4-scale water–oil physical model combined with numerical simulation to investigate the effects of elliptical and circular submerged entry nozzles on slag entrainment behavior in a wide slab mold under different casting speeds and immersion depths. High-speed cameras were used to visualize meniscus fluctuations and oil droplet entrainment processes. An alternating control variable method was employed to quantitatively delineate a slag-free “safe zone” and a “slag entrainment zone” where oil droplets fall, determining the critical casting speed and critical immersion depth under different operating conditions. The results show that, given the nozzle immersion depth and slag viscosity, the maximum permissible casting speed range without slag entrainment can be obtained, providing a reference for industrial production parameter control. The root mean square (RMS) of surface fluctuations was introduced to characterize the activity of the meniscus flow. It was found that the RMS value decreases with increasing nozzle immersion depth and increases with increasing casting speed, showing a good correlation with the frequency of slag entrainment. Numerical simulation results show that compared with elliptical nozzles, circular nozzles form a more symmetrical flow field structure in the upper recirculation zone, with a left–right vortex center deviation of less than 5%, resulting in higher flow stability near the meniscus and thus reducing the risk of slag entrainment. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by persistent memory impairment and complex molecular and cellular pathological changes in the brain. Current treatments, including acetylcholinesterase inhibitors and memantine, only help with symptoms for a short time and do not stop the disease from getting worse. This is mainly because these drugs do not reach the brain well and are quickly removed from the body. The blood–brain barrier (BBB) restricts the entry of most drugs into the central nervous system; therefore, new methods of drug delivery are needed. Nanotechnology-based drug delivery systems (NTDDS) are widely studied as a potential approach to address existing therapeutic limitations. Smart biosensing nanoparticles composed of polymers, lipids, and metals can be engineered to enhance drug stability, improve drug availability, and target specific brain regions. These smart nanoparticles can cross the BBB via receptor-mediated transcytosis and other transport routes, making them a promising option for treating AD. Additionally, multifunctional nanocarriers enable controlled drug release and offer theranostic capabilities, supporting real-time tracking of AD treatment responses to facilitate more precise and personalized interventions. Despite these advantages, challenges related to long-term safety, manufacturing scalability, and regulatory approval remain. This review discusses current AD therapies, drug-delivery strategies, recent advances in nanoparticle platforms, and prospects for translating nanomedicine into effective, disease-modifying treatments for AD. Full article