Search Results (1,887)

Aggregates of misfolded α-synuclein proteins are key markers of Parkinson’s disease. The protein α-synuclein (aSyn) is an intrinsically disordered protein (IDP) and therefore lacks a single stable 3D structure, instead sampling multiple conformations in solution. It is primarily located in presynaptic terminals and is thought to help regulate synaptic vesicle trafficking and neurotransmitter release. ASyn proteins have three domains: an N-terminal domain, a hydrophobic non-amyloid-β component (NAC) core implicated in aggregation, and a proline-rich C-terminal domain. Asyn proteins with truncated C-terminal domains are known to be prone to aggregation and suggest that understanding domain–domain interactions in aSyn monomers could help elucidate the role of the flanking domains in modulating protein structure. To this end, we used Gaussian accelerated molecular dynamics (GAMD) to simulate wild-type (WT), N-terminal truncated (ΔN), C-terminal truncated (ΔC), and isolated NAC domain (isoNAC) aSyn protein variants. Using clustering and contact analysis, we found that removal of the N-terminal domain led to increased contacts between NAC and C-terminal domains and the formation of inter-domain β-sheets. Removal of either flanking domain also resulted in increased compactness of every domain. We also found that the contacts between flanking domains in the WT protein result in an electrostatic potential (ESP) that may lead to favorable interactions with anionic lipid membranes. Removal of the C-terminal domain disrupts the ESP in a way that could result in over-stabilized protein–membrane interactions. These results suggest that cooperation between the flanking domains may modulate the protein’s structure in a way that helps maintain elongation and creates an ESP that may aid favorable interactions with the membrane. Full article

Composite materials are widely utilized for their excellent properties; however, the mismatch in phase response during processing often induces surface and subsurface damage. While reducing the cutting depth is a common strategy to improve quality, it shifts the material removal mechanism from shear to ploughing–extrusion, which can, in fact, degrade the final surface integrity. Energy field assistance is a promising approach to suppress this issue, yet its underlying mechanism remains insufficiently understood. This study investigates high-silicon aluminum alloy by combining turning experiments with molecular dynamics simulations to elucidate the origin and evolution of damage under different energy fields, establishing a correlation between microscopic processes and observable defects. In conventional turning, damage propagation is driven by particle accumulation and dislocation interlocking. Ultrasonic vibration softens the material and confines plastic deformation to the near-surface region, although excessively high transient peaks can lead to process instability. Laser remelting turning disperses stress within the remelted layer, significantly inhibiting defect expansion, but its effectiveness is highly sensitive to variations in cutting depth. The hybrid approach, laser remelting ultrasonic vibration turning, leverages the dispersion buffering effect of the remelted layer and the localized plastic deformation from ultrasonication to reduce peak loads, control deformation depth, and suppress defects, while simultaneously mitigating the depth sensitivity of damage and maintaining removal efficiency. This work clarifies the mechanism by which a composite energy field controls damage in the micro-cutting of high-silicon aluminum alloy, providing practical guidance for the high-quality machining of composite materials. Full article

Litchi is an important subtropical fruit, highly valued by consumers for its vibrant color and distinctive flavor. B-box (BBX) proteins, which are zinc finger transcription factors, play a crucial role in regulating plant growth, development, and stress responses. Nevertheless, the specific function of BBX genes in the development and coloration of litchi fruit remains inadequately understood. In this study, 21 LcBBX genes (designated as LcBBX1-LcBBX21) were identified within the litchi genome. These genes were categorized into five sub-families based on phylogenetic analysis and were found to be unevenly distributed across 12 chromosomes. Promoter analysis revealed a rich presence of light-responsive elements, such as the G-box, and abscisic acid (ABA) responsive elements, including ABRE, within the promoter regions of LcBBX genes. Protein–protein interaction predictions indicated that the majority of LcBBX genes have the potential to interact with the light-responsive factor HY5. Transcriptome analysis and qRT-PCR results demonstrated that LcBBX genes exhibit tissue-specific expression patterns. Notably, most LcBBX genes were highly expressed prior to fruit coloration, whereas LcBBX4 and LcBBX10 were upregulated during the fruit coloration phase. Furthermore, LcBBX1/4/6/7/15/19 were upregulated in response to light following the removal of shading. The findings suggest that LcBBX4 may directly regulate anthocyanin biosynthesis in litchi pericarp. This study provides critical insights into the molecular mechanisms underlying litchi fruit development and coloration. Full article

Cornelia de Lange Syndrome (CdLS) is a rare multisystem developmental disorder caused primarily by mutations in cohesin complex genes, including RAD21. Psoriasis is a chronic inflammatory skin disease linked to immune dysregulation, notably involving TNFAIP3 (A20), a negative regulator of NF-κB signaling. Although case reports have suggested a possible coexistence of CdLS and psoriasis, the underlying molecular basis has remained unexplored. Here we report the first case of molecular co-occurrence of CdLS and generalized pustular psoriasis in a patient with novel heterozygous nonsense variant in RAD21 (c.1306C>T, p.Gln436*), pathogenic for CdLS type 4, and a previously unreported truncating variant in TNFAIP3 (c.2199C>A, p.Cys733*), predicted to disrupt NF-κB regulation and classified as a variant of uncertain significance. Structural protein modeling showed significant conformational disruption in RAD21 and partial truncation of the ZnF domains of TNFAIP3, supporting their functional impact. This study is the first to suggest a possible molecular mechanism that may explain the rare co-occurrence of CdLS and psoriasis: RAD21 deficiency disrupts chromatin architecture and immune gene regulation, while TNFAIP3 loss-of-function removes critical NF-κB inhibition, resulting in synergistic developmental and inflammatory phenotypes. Secondary transcriptomic data analysis further suggests that RAD21 knockdown may downregulate TNFAIP3 expression, providing a possible mechanistic intersection. Our findings provide the first molecular evidence linking RAD21 and TNFAIP3, introducing a novel pathogenic hypothesis connecting cohesin dysfunction and immune dysregulation. This work expands the mutational spectrum of both genes and opens a new avenue for understanding developmental-inflammatory disease overlap. Full article

New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales represent a major therapeutic challenge due to their resistance to nearly all β-lactams and frequent co-resistance to other antibiotic classes, leaving clinicians with few effective options. These challenges are amplified in orthopedic infections with hardware involvement, where biofilm formation and the need for prolonged antimicrobial therapy limit success. We describe a 55-year-old female with a history of right type 3 open pilon fracture complicated by hardware failure and revision, who presented with septic tibial nonunion and chronic drainage. During this admission, she underwent irrigation and debridement with hardware removal and intramedullary nail placement. Cultures grew Enterobacter cloacae complex resistant to meropenem, ceftazidime–avibactam, meropenem–vaborbactam, and cefiderocol, as well as Candida parapsilosis. Molecular testing confirmed NDM production, while reference testing showed susceptibility to aztreonam–avibactam (ATM-AVI). The patient was treated with ATM-AVI plus micafungin, achieving clinical stability within three days. Due to outpatient administration barriers with ATM-AVI, the patient was transitioned to eravacycline and micafungin. At eight-week follow-up, the patient remained clinically improved without relapse or adverse effects. This case highlights ATM-AVI as a critical therapy for NDM-producing orthopedic infections involving hardware and supports eravacycline as a feasible step-down option in outpatient management. Full article

Mesoporous materials have attracted increasing attention due to their ordered pore systems; tunable surface chemistry; and versatile applications in catalysis, adsorption, and environmental technologies. Among them, SBA-15 stands out for its large surface area, uniform mesopores, and high hydrothermal stability, which make it a promising platform for gas adsorption and mass transport studies. This review examines the functionalization of SBA-15 through strategies such as post-synthesis grafting and co-condensation, focusing on the introduction of amines, thiols, and organometallic species that enhance selectivity, adsorption capacity, and thermal stability. The discussion integrates classical diffusion models, including Fickian and Knudsen transport, with more advanced approaches such as the Maxwell–Stefan formalism, to describe molecular transport within mesoporous networks and highlight the role of van der Waals interactions in gas capture processes. Special emphasis is placed on the relationship between structural features and diffusive behavior, supported by recent advances in computational modeling and spectroscopic validation. Applications in CO₂ capture, heterogeneous catalysis, drug delivery, and environmental remediation are critically assessed to illustrate the versatility of functionalized SBA-15. This review concludes by outlining future perspectives on the rational design of hierarchical and multifunctional mesoporous materials for clean energy conversion, pollutant removal, and biomedical applications. Full article

Microplastic particles with a size of less than 5 mm make up a significant component of the plastic pollution in freshwater and the ocean. This study was designed to investigate the effects of eight-week exposure to high-molecular-weight polyvinyl chloride (HMW-PVC) on young rats. A total of 40 rats were divided into two assay groups of 15 rats (Group 1, Group 2, a total of 30 rats) and a control group of 10 rats. The rats in the first and second assay groups were fed with food containing HMW-PVC at rates of 1 and 2% of their weight, respectively. The control group was fed food without HMW-PVC. The rats’ weights were recorded every 15 days. After eight weeks of feeding, the rats’ intestines, kidneys, and livers were removed and underwent histopathological examinations. Additionally, mRNA expression levels of Cyp3A2, Pepck, and Fasn genes in the liver, UT-A1, UT-A2, renin, and Cyp27B1 genes in the kidney, and Muc2, Fabp2, and PepT1 genes in the intestine were determined by using the RT-PCR technique. Our study revealed that rats exposed to microplastic particles exhibited non-significant weight loss and obvious organ degeneration. Furthermore, mRNA expression levels of the examined genes were either elevated or suppressed by regular exposure to high-molecular-weight PVC. Full article

Estrogen is a key regulator of skeletal muscle growth and metabolism in birds, yet its specific roles in female chickens remain poorly defined. To address this gap, we established an estrogen-deficient model by surgically removing the ovaries of Wuding hens, a Chinese indigenous slow-growing breed. Growth traits, carcass yield, and meat quality were evaluated across different ages, complemented by histological examination, serum biochemical analysis, and multi-omics approaches (transcriptomics, proteomics, and lipidomics). Ovariectomized hens maintained somatic growth for a longer period and reached greater body weight and carcass yield at 330 days compared with intact controls. Thigh muscle tenderness was also enhanced in the absence of estrogen, despite no long-term differences in muscle fiber morphology. Lipidomic analysis revealed a transient increase in intramuscular triglyceride content at mid-growth (240 days), pointing to altered lipid storage and distribution. Integrated omics profiling further demonstrated significant changes in the mitogen-activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) signaling pathways, accompanied by differential expression of key metabolic and structural genes, including mitogen-activated protein kinase 8 (MAPK8), fatty acid binding protein 4 (FABP4), ankyrin 1 (ANK1), and coenzyme Q6 monooxygenase (COQ6). These molecular adjustments suggest that estrogen withdrawal triggers broad reprogramming of muscle signaling and lipid metabolism. Overall, this study highlights the multifaceted role of estrogen in coordinating growth, muscle quality, and lipid homeostasis in hens and provides a functional model for studying estrogen deficiency in poultry with implications for meat quality improvement. Full article

The efficient removal of natural organic matter (NOM) through a coagulation process is crucial for improving the quality of drinking water. Recent studies have focused on the interaction between NOM and coagulants during the floc formation and aging process. Therefore, based on the relevant literature from the past few decades, this review focuses on changes in floc activity during floc formation and aging at a molecular level. It systematically clarifies the mechanisms and factors influencing floc formation and aging and summarizes the characterization techniques for NOM and flocs. Notably, the interaction between NOM and coagulant flocs is determined by the presence of carboxyl groups and hydroxyl groups on NOM and hydroxyl groups (η-OH) and water molecules (η-OH₂) on coagulant flocs. Aging involves the transformation of coagulant species and an increase in floc crystallinity, which leads to the absorption or release of organic matter. Although numerous analytical techniques currently offer new insights into the interaction between coagulants and NOM, in situ characterization techniques remain limited. This review provides a theoretical foundation for the full life cycle assessment of NOM in coagulation processes, which is of great significance for advancing drinking water technologies and achieving carbon neutrality goals. Full article

The intensification of industrialization and increasing energy consumption have led to elevated emissions of hazardous gases such as NO, NO₂, and SO₂, making their efficient capture and removal crucial for environmental remediation. In this work, first-principles calculations were employed to systematically investigate the adsorption behavior of these gases on single-atom-decorated (Sc, Ti, and V) 1T-ZrS₂ monolayers. The results indicate that the transition metal atoms preferentially occupy the hexagonal hollow sites of ZrS₂, forming an approximately octahedral coordination field and exhibiting characteristic d-orbital splitting. During gas adsorption, the decorated systems exhibit pronounced metal-to-adsorbate charge donation and strong d-p hybridization, indicative of strong chemisorption. Notably, Ti-ZrS₂ exhibits the strongest adsorption toward NO₂, inducing partial molecular dissociation and suggesting catalytic activity, whereas Sc- and V-decorated systems predominantly maintain molecular adsorption. Recovery time calculations indicate that the adsorption processes are comparatively stable, making these systems suitable for gas capture and pollution abatement. Overall, single-atom decoration provides an effective strategy to modulate the electronic structure and gas interactions of ZrS₂, highlighting its potential as an efficient gas scavenger for NO, NO₂, and SO₂. Full article

Cannabis plants are susceptible to microbial contamination, including fungi capable of producing harmful mycotoxins. The presence of these toxins in cannabis products poses serious health risks, especially when used for medical purposes in immunocompromised people. This study evaluated the presence of fungi and mycotoxins in dried cannabis buds following gamma irradiation, using culture-based techniques, PCR/qPCR, and ELISA. Irradiation significantly reduced fungal and bacterial loads, eliminating culturable bacteria but did not achieve complete sterilization. Viable spores of toxigenic fungal genera, such as Aspergillus, Penicillium, and Fusarium, persisted. Sequencing of ITS amplicons revealed dominant mycotoxigenic fungi in non-irradiated (NR), irradiated (IR) and licensed producer (LP) samples, while next-generation sequencing (NGS) revealed additional non-culturable toxigenic species. PCR/qPCR detected biosynthetic genes for aflatoxins, trichothecenes, ochratoxins, and deoxynivalenol across all samples, with gene copy numbers remaining stable post-irradiation, suggesting DNA damage without full degradation. ELISA confirmed aflatoxin, ochratoxin, DON, and T2 toxins in both IR and LP samples at variable concentrations. While LP samples showed lower microbial counts and gene abundance, residual DNA and toxins were still detected. Our study shows that while irradiation decreases microbial loads, it does not completely remove toxigenic fungi or their metabolites. Ensuring the safety of cannabis products necessitates a multifaceted assessment that incorporates cultural, molecular, and immunological techniques, in parallel with more stringent microbial standards during production stage. Full article

To address the challenge of treating reverse osmosis concentrate (ROC) in municipal wastewater reclamation processes, this study systematically investigated changes in ozone demand, organic compound molecular weight distribution, UV/fluorescence characteristics, and microalgal growth potential during ozone treatment of ROC. The ROC contained fast-reacting substances and had an instantaneous ozone demand of 6.3 mg/L. The chemical oxygen demand (COD) and total organic carbon were partially removed, and the COD/five-day biochemical oxygen demand ratio increased slightly during the ozonation process. The molecular weight components shifted considerably during ozonation: the 300 Da–1000 Da components became dominant (51.6–72.3%), while the 1000 Da–4000 Da and <300 Da components were partially or completely removed. The maximum absorbance of the ROC peaked at 270 nm. At an ozone dosage of 84 mg/L, the UV₂₅₄ and UV₂₇₀ removal rates reached 76.9% and 86.5%, respectively. The three-dimensional fluorescence spectra showed that ozone effectively removed tryptophan-type aromatic proteins, fulvic acid-type substances, aromatic proteins, soluble microbial metabolites, and humic acid-type substances from the concentrate (84.6–88.9%), but only removed a minimal amount of the tyrosine-type aromatic protein (7.4%). The UV₂₅₄ at different molecular weights and the fluorescence area integrals across regions declined rapidly initially, then slowed gradually, correlating with the rapid reaction of UV/fluorescence chromophore-containing substances in ROC. Studies on microalgal growth potential indicate that ozonation increased the maximum algal density (K) in ROC (48.9–91.7%), while ozone/coagulation effectively reduced K (35.1–76.6%). This occurs because ozone converts organic phosphonate antiscalants in ROC into more readily absorbable inorganic phosphorus, whereas ozone/coagulation effectively removes total phosphorus from water. These results can guide the safe disposal of ROC and facilitate sustainable reclamation of municipal wastewater. Full article

Mechanical ventilation is a critical intervention in patients who cannot spontaneously maintain adequate oxygenation and remove carbon dioxide. However, it can also lead to severe lung injury via volutrauma, barotrauma, atelectrauma and biotrauma, and it can worsen existing lung disease such as acute respiratory distress syndrome. Ventilator-associated lung injury, the clinical manifestations of lung damage associated with mechanical ventilation, can trigger systemic inflammatory cascades that contribute to multi-organ failure. The utilization of lung-protective ventilation strategies helps to minimize further injury to the lungs during mechanical ventilation and improve survival rates. This review discusses the pathophysiology of ventilator-associated lung injury, including cellular and molecular responses, its systemic effects, risk factors, clinical presentation and diagnosis, protective strategies, and emerging therapies. It incorporates interdisciplinary advances, from novel pharmacologic and stem-cell therapies coupled with artificial intelligence and machine learning systems to provide a framework for the prevention of ventilator-associated lung injury that moves beyond purely mechanical considerations. Full article

Background: Preeclampsia is a complex hypertensive disorder of pregnancy associated with significant maternal and foetal morbidity and mortality. Its pathogenesis involves placental hypoxia, oxidative stress, and impaired trophoblast invasion. Recent evidence highlights the role of microRNAs, particularly microRNA-210 (miR-210), in the molecular disruptions underlying preeclampsia. Aim: This study aims to explore the pathogenic, diagnostic, and therapeutic significance of miR-210 in preeclampsia, with emphasis on its molecular mechanisms, biomarker potential, and prospects as a therapeutic target. Methods: A systematic narrative review was conducted following PRISMA guidelines. A total of 498,184 articles were identified through eight scientific databases, and, after duplicate removal and eligibility screening, 111 peer-reviewed studies published between 2015 and 2025 were included in the final analysis. The selected literature focused on miR-210’s expression in placental tissue and maternal circulation, its molecular targets, and its clinical relevance. Results: miR-210 is consistently upregulated in preeclamptic placentas and maternal plasma. It contributes to shallow trophoblast invasion, impaired angiogenesis, mitochondrial dysfunction, and the activation of a hypoxia-induced HIF-1α feedback loop. These mechanisms are central to the disease’s pathophysiology. Clinically, miR-210 demonstrates high stability in circulation and early detectability, making it a promising diagnostic and prognostic biomarker. Experimental models have also demonstrated the therapeutic potential of miR-210 inhibition using antisense oligonucleotides or HIF-1α modulators. Conclusions: miR-210 is both a marker and mediator of preeclampsia. Its integration into diagnostic protocols and therapeutic strategies, alongside clinical validation and standardisation, may enhance early detection and personalised care in high-risk pregnancies. Full article

Coagulation–flocculation, historically reliant on simple inorganic salts, has evolved into a technically sophisticated process that is central to the removal of turbidity, suspended solids, organic matter, and an expanding array of micropollutants from complex wastewaters. This review synthesizes six decades of research, charting the transition from classical aluminum and iron salts to high-performance polymeric, biosourced, and hybrid coagulants, and examines their comparative efficiency across multiple performance indicators—turbidity removal (>95%), COD/BOD reduction (up to 90%), and heavy metal abatement (>90%). Emphasis is placed on recent innovations, including magnetic composites, bio–mineral hybrids, and functionalized nanostructures, which integrate multiple mechanisms—charge neutralization, sweep flocculation, polymer bridging, and targeted adsorption—within a single formulation. Beyond performance, the review highlights persistent scientific gaps: incomplete understanding of molecular-scale interactions between coagulants and emerging contaminants such as microplastics, per- and polyfluoroalkyl substances (PFAS), and engineered nanoparticles; limited real-time analysis of flocculation kinetics and floc structural evolution; and the absence of predictive, mechanistically grounded models linking influent chemistry, coagulant properties, and operational parameters. Addressing these knowledge gaps is essential for transitioning from empirical dosing strategies to fully optimized, data-driven control. The integration of advanced coagulation into modular treatment trains, coupled with IoT-enabled sensors, zeta potential monitoring, and AI-based control algorithms, offers the potential to create “Coagulation 4.0” systems—adaptive, efficient, and embedded within circular economy frameworks. In this paradigm, treatment objectives extend beyond regulatory compliance to include resource recovery from coagulation sludge (nutrients, rare metals, construction materials) and substantial reductions in chemical and energy footprints. By uniting advances in material science, process engineering, and real-time control, coagulation–flocculation can retain its central role in water treatment while redefining its contribution to sustainability. In the systems envisioned here, every floc becomes both a vehicle for contaminant removal and a functional carrier in the broader water–energy–resource nexus. Full article