Search Results (1,057)

Histone-modifying enzymes and histone post-translational modifications (PTMs) play key roles in the organization (euchromatin versus heterochromatin) and function (active versus silenced genes) of chromatin. The abundance and activity of these enzymes, along with their associated histone PTMs, are often altered in cancer cells, leading to deregulated gene expression. The expression of the KMT2A-MLLT3 protein, resulting from a chromosomal translocation in mixed-lineage leukemia (MLL), a subtype of acute myeloid leukemia, augments transcription elongation, promoting the expression of HOXA9 and MEIS1, genes that play critical roles in MLL development. Bortezomib, a proteasome inhibitor, has been effective at treating various cancers. In this study, we compared the impact of bortezomib on histone PTMs in the MLL cell line MOLM-13 and the chronic myeloid leukemic (CML) cell line K562. We report that MOLM-13 had a greater level of histone H2B monoubiquitinated at lysine 120 (H2BK120ub) and histone H3 dimethylated at lysine 79 (H3K79me2) (modifications involved in elongation) and similar levels of histone H2A monoubiquitinated at lysine 119 (H2AK119ub). Bortezomib treatment resulted in significant reductions in H2BK120ub and H2AK119ub levels, as well as in transcript levels of genes involved in MLL development. Full article

Background: Pathogenic variants in genes that cause skeletal dysplasias may, instead of producing classic findings, present in children with a phenotype whose hip radiographs resemble bilateral Legg-Calvé-Perthes disease (LCPD). Objectives: This study aims to investigate the efficacy of genetic diagnosis in children with waddling gait or joint pain and radiological evidence of hip dysplasia mimicking bilateral LCPD. Methods: Forty children with bilateral femoral head dysplasia from 36 families were included in the study. Exome sequencing was performed, and all identified variants were confirmed within the families by Sanger sequencing. Results: Twelve pathogenic or likely pathogenic variants were identified: six in COL2A1, two in COL9A1, and one each in RPL13, EIF2AK3, DNAJC21, and ARSK; six are novel. The diagnostic yield was 33.3% (12/36) in 12 families. Additionally, variants of uncertain significance (VUS), proposed as causative, were detected in five families (5/36:13.9%): two in COL11A1 and one each in COL9A3, COL11A2, and ARSK. Based on bilateral epiphyseal dysplasia of the femoral head, it was observed that seven families may be compatible with mild spondyloepiphyseal dysplasia and six families may have Stickler syndrome. Notably, among these, three children carrying closely localized pathogenic/likely pathogenic variants in COL2A1 shared a novel phenotype characterized by short stature and bilateral irregular femoral heads. In four families, EIF2AK3, DNAJC21, and ARSK were also responsible for the ultra-rare disorders Wolcott-Rallison syndrome, bone marrow failure syndrome 3, and mucopolysaccharidosis 10, respectively. Conclusions: This study, for the first time, investigated the frequency of associated genes in a pediatric cohort with bilateral hip dysplasia resembling LCPD, providing important information for pathogenesis and differential diagnosis. Full article

Understanding the long-term spatiotemporal dynamics of soil nutrients in land consolidation areas is essential for sustainable land management. In this study, the changes in soil organic matter (SOM), available nitrogen (AN), available phosphorus (AP), available potassium (AK), and soil pH from 1980 to 2023 in the land consolidation area of Anyi County, China, were investigated. A random forest (RF) model was developed using multisource environmental variables, including climate, topography, remote sensing, vegetation, parent material, distance to rivers, and land use. The results revealed three key findings. First, while land consolidation significantly increased overall soil nutrient levels, trends for individual nutrients were highly variable: AP and AK continuously increased over the 40-year period. SOM and AN increased after consolidation but decreased in later years. This process was accompanied by systematic soil acidification. Second, land consolidation substantially restructured the spatial patterns of soil nutrients. SOM and AN became more homogeneously distributed, whereas AP and AK showed increased variability. High-value nutrient areas shifted from contiguous expansion in the early stages to local aggregation and patchy fragmentation over the long term. Third, the RF model demonstrated high predictive accuracy (R² = 0.70 for pH, 0.68 for SOM, 0.63 for AP, and 0.54 for AK), with variable importance analysis identifying distinct environmental drivers for each nutrient. These findings provide a scientific basis for precision fertilization and evidence-based land consolidation planning. Full article

Photodynamic therapy (PDT) is a cornerstone non-invasive modality for keratinocytic precancers and non-melanoma skin cancer (NMSC), leveraging selective photosensitizer accumulation, light activation, and reactive oxygen species (ROS) generation. This narrative review synthesized literature from major databases (2010–2025) to comprehensively evaluate PDT’s molecular mechanisms, innovative optimization protocols, and clinical efficacy across actinic keratosis (AK), field cancerization, Bowen’s disease (BD), basal cell carcinoma (BCC), and invasive squamous cell carcinoma (cSCC). The evidence highlights frontline clinical maturity and excellent cosmetic outcomes for superficial lesions (AK, field cancerization, superficial BCC, and BD), with daylight PDT offering a virtually painless alternative for widespread dysplasia. However, therapeutic reliability decreases in thick nodular, pigmented, or high-risk lesions due to optical barriers and tissue hypoxia. To overcome these limitations, advanced physical and chemical enhancements—such as ablative fractional lasers, iron chelators, epigenetically enhanced PDT (ePDT), and targeted nanocarriers—are actively reshaping drug delivery and cellular susceptibility. Furthermore, cyclic PDT serves as an indispensable tissue-sparing intervention for organ transplant recipients and Gorlin syndrome patients. In conclusion, while PDT is highly effective for superficial neoplasias, precise histopathological stratification and the integration of nanomedicine are critical to overcoming current biological barriers in aggressive dermatological malignancies. Full article

To explore low-carbon spring wheat production strategies for the ecologically fragile Qinghai Plateau, a two-year field experiment was conducted using a split-plot design. The main plots were set with three nitrogen (N) application levels: N0 (0 kg·ha⁻¹, no N input), N1 (157.5 kg·ha⁻¹, 30% N reduction relative to conventional rate), and N2 (225 kg·ha⁻¹, the conventional rate). The subplots comprised four green manure mixed cropping patterns: sole cropped common vetch (CK), common vetch mixed with hull-less barley (HB), common vetch mixed with hairy vetch (HV), and common vetch mixed with rapeseed (RS). Averaged across green manure treatments, N1 reduced global warming potential (GWP) by 14.56% and greenhouse gas intensity (GHGI) by 16.89% compared with N2. Under the N1 treatment, compared with CK, RS reduced cumulative CO₂ emissions by 7.77% and GWP by 7.45%, maintained wheat grain yield comparable to those under N2, and obtained the minimum GHGI which was 2.92% lower than CK. Regarding soil properties, all green manure patterns significantly increased soil available phosphorus (AP) and available potassium (AK) compared with CK. Specifically, HB increased AP by 12.81% and AK by 16.38%, and RS also increased AP by 4.37% and AK by 2.36%. In addition, HB enhanced soil organic matter (SOM) by 5.85%, ammonium nitrogen (NH₄–N) by 8.13%, and nitrate nitrogen (NO₃–N) by 4.34%. Soil NH₄–N and NO₃–N were identified as key drivers of GHGI across treatments. On the Qinghai–Tibet Plateau, a 30% N reduction combined with target-oriented green manure mixtures—RS for emission mitigation and HB for high yield and fertility—offers a viable low-carbon strategy for spring wheat production. Full article

This study established three intercropping densities of cassava and chili (chili plant spacing of 0.4 m, 0.5 m, and 0.6 m, denoted as IA, IB, and IC, respectively), using cassava monoculture (MC) and chili monoculture (MP) as controls, to systematically investigate differences in soil biochemical properties and soil bacterial community structure under different cassava−chili cropping systems. The results showed that soil pH, catalase activity, and acid phosphatase activity were higher in the IB and IC treatments than in the monoculture treatments, while alkali-hydrolyzable nitrogen (AN), available phosphorus (AP), and available potassium (AK) contents were lower in the IA and IC treatments compared to the monoculture treatments. Alpha diversity was higher in the intercropping systems than in the monoculture systems, and the soil bacterial communities exhibited greater richness and diversity. In the intercropping systems, the relative abundances of Verrucomicrobiota, Gemmatimonadota, and the common dominant soil genus Candidatus_Udaeobacter increased, while those of Actinobacteriota, Proteobacteria, and the genera Acidothermus and Chujaibacter decreased. Redundancy analysis indicated that the soil bacterial community was significantly influenced by soil catalase activity and total nitrogen. In summary, cassava−chili intercropping enhances soil nutrient levels and enzyme activity while reshaping the structure of the soil bacterial community. Full article

Cutaneous leishmaniosis (CL) remains a major neglected tropical disease, with current therapies constrained by toxicity, high cost, and variable efficacy. Here, we evaluated an immunochemotherapy strategy combining topical amphotericin B (AmB) with the therapeutic DNA vaccine HisAK70 in a murine model of Leishmania major infection. BALB/c mice were subcutaneously infected and treated with topical AmB cream alone, AmB plus HisAK70, or paromomycin (PM) as a reference therapy. Therapeutic efficacy was assessed through lesion progression, parasite burden in draining lymph nodes and spleen, and immunological markers associated with parasite control. Both PM and the combined AmB + HisAK70 treatment significantly reduced lesion progression and markedly decreased parasite burden compared with infected controls, demonstrating effective control of local infection and systemic dissemination. Importantly, the combination therapy enhanced the efficacy of AmB alone, supporting the beneficial contribution of vaccine-driven immune modulation to therapeutic outcome. Therapeutic efficacy was associated with reduced arginase activity in infected tissues and an increased IFN-γ/IL-4 ratio, indicative of a protective Th1-oriented immune response. Together, these findings highlight immunochemotherapy as a promising strategy for CL treatment, integrating localized topical drug delivery with targeted immune activation to improve therapeutic efficacy while potentially reducing systemic toxicity. Full article

Davis critiqued a recent review, “Eastern North American Monarch Butterfly Conservation Needs and Opportunities: What the Science Tells Us”. He argued that Eastern North American monarch numbers in the summer have not declined, despite dramatic declines in the area covered by this population in Mexico during the winter. These declines in winter numbers, he said, can be explained by increasing mortality during the fall migration and subsequent density-dependent increases the following spring. A strong impetus for these arguments appears to be Davis’s concern that recommendations by “certain circles” of the monarch research community could steer conservation funding toward a species that does not need our help. Here, we address these concerns, and note that there is no evidence that conservation funding focused on providing breeding habitat for monarchs detracts from conservation for other species in need of help, or from efforts to support migrating monarchs. Full article

Soil texture is a key determinant shaping bacterial communities in vineyard ecosystems, yet how different soil textures modulate bacterial characteristics in rhizosphere versus bulk soils during grapevine growth remains poorly understood. This study collected rhizosphere and bulk soil samples from five commercial Vitis vinifera cv. Cabernet Sauvignon vineyards in the eastern piedmont of Helan Mountain, Ningxia, China, spanning three distinct textures (gravelly, calcareous, and aeolian sandy soils). Shotgun metagenomic sequencing, soil physicochemical analysis, and four soil enzyme activity (alkaline phosphatase, urease, catalase, and invertase) measurements were conducted, using PERMANOVA and RDA to identify dominant driving factors. The results showed that bacteria accounted for 97.6% of all annotated sequences, representing the dominant group in soil microbial communities. Significant differences in bacterial abundance and alpha diversity (Chao1, ACE, Shannon, and Simpson) were observed in bulk soils across textures, whereas rhizosphere soils showed significant abundance differences but similar diversity levels. However, the 50 cm bulk soil sampling distance may have attenuated the true rhizosphere effect, and these findings should be interpreted with this methodological constraint in mind. Notably, bacterial community structure differed significantly between soils of the same pedogenic type but different textures, confirming that soil texture, rather than pedogenic classification, is the primary driver. Thirteen dominant bacterial phyla (>1% relative abundance) were identified, with Proteobacteria (47.7%), Actinobacteriota (22.9%), and Acidobacteriota (6.5%) as the main taxa. Mantel tests revealed significant correlations between nitrogen, phosphorus, organic matter contents and enzyme activities in rhizosphere soils (r ≥ 0.4, p < 0.01). RDA indicated that total phosphorus (TP), organic matter (OM), alkali-hydrolyzable nitrogen (AN), Mg, pH, available K (AK), and enzyme activities were key drivers of bacterial community structure (p < 0.05). Annotated metabolic functions based on KEGG orthology indicated lower overall metabolic pathway abundances in gravelly soils compared to calcareous and aeolian sandy soils. In conclusion, soil texture, rather than broad pedogenic classification, primarily shapes vineyard bacterial communities, providing a theoretical basis for precision viticulture and sustainable soil management. Full article

Mitochondrial dysfunction and impairment of high-energy phosphate transfer are increasingly recognised as shared pathogenic features across neurological disorders. Because neurons require large amounts of ATP to sustain synaptic transmission, ion gradients, axonal transport, and intracellular signalling, they are especially vulnerable to disturbances in energy metabolism. Neurological dysfunction, therefore, cannot be explained solely by reduced mitochondrial ATP production. It also involves failure of the creatine kinase/phosphocreatine (CK/PCr) and adenylate kinase/AMP-activated protein kinase (AK–AMPK) systems, which normally support local ATP buffering, high-energy phosphate transfer, and intracellular energy homeostasis. In parallel, extracellular ATP-dependent purinergic dysregulation contributes to glia-mediated inflammation, synaptic dysfunction, and cell death, linking intracellular energy failure to abnormal intercellular signalling. In this review, we integrate these mechanisms into a shared pathological continuum of disrupted energy homeostasis. We then compare Alzheimer’s disease, Parkinson’s disease, and epilepsy as representative disorders with shared and disease-specific manifestations of this continuum, characterised respectively by chronic cerebral energy crisis, selective metabolic fragility, and acute energy overload with purinergic dysregulation. Finally, we discuss how this comparative perspective may help identify shared therapeutic opportunities while preserving disorder-specific interpretation. Full article

This study empirically investigates the interplay between two foundational knowledge frameworks in architectural design education: the Vitruvian triad (Architectural Knowledge Traditions—AkT) and the Triple Bottom Line (Sustainability Knowledge Traditions—SkT). Focusing on Ethiopia as a case of non-industrial urbanization in the Global South, where socio-economic realities diverge from Global North contexts, the research examines how the six variables within these frameworks interact within pedagogical practice. Using a mixed-methods approach, the study combines questionnaires from senior architectural design instructors across 13 universities with a critical content analysis of university exit model-examinations. Analyzed through specific theoretical lenses, findings reveal a critical divergence: while instructors demonstrate strong theoretical awareness of complementarity between the two traditions, their model-assessment focuses contradict this stance. The analysis reveals a fundamental skew toward an inherited environmental doctrine, where the Venustas–Environment coupling dominates at the expense of social and economic survival imperatives. The study concludes that these “knowledge overlaps” do not inherently warrant successful integration but instead reflect a “design–reality gap” fueled by globalized doctrines and knowledge coloniality. The study concludes by providing the empirical grounding necessary to dismantle the often-universalized norms, arguing for a localized matrix that centers epistemological autonomy within architectural education in the Global South. Full article

This paper addresses the challenges of life prediction and reliability assessment for ball screws under complex operating conditions by proposing a reliability prediction model that incorporates full-life fatigue damage. First, a full-life fatigue life prediction model encompassing the three stages of crack initiation, propagation, and fatigue cumulative spalling is developed. This model comprehensively considers the effects of material properties, geometric parameters, and loading history, enabling a systematic description of the fatigue process of ball screws from initial use to final failure. Based on this life prediction model, an enhanced adaptive Kriging–Monte Carlo simulation (E-AK-MCS) method is introduced to construct a surrogate model, which efficiently solves the high-dimensional nonlinear limit state function, thereby enabling accurate reliability assessment and parameter sensitivity analysis. Experimental results demonstrate that the proposed model achieves an average life prediction accuracy of 94.15% for the 8020 and 5005 specification ball screws, indicating its preliminary engineering applicability under the tested conditions. Reliability analysis indicates that ball diameter fracture toughness, and initial crack size are key factors influencing service reliability. This research provides systematic theoretical methods and technical support for the accurate life prediction, reliability design, and process optimization of ball screws. Full article

Assessment of upper-limb kinematics is essential in clinical practice for diagnosis, rehabilitation monitoring, and treatment personalization. Markerless Motion Capture (MMC) systems, such as the Microsoft Azure Kinect (AK), offer a low-cost and time-efficient alternative to marker-based systems. However, while AK accuracy has been extensively studied for lower-limb movements, its performance for upper-limb analysis—especially under clinically relevant, suboptimal conditions—remains underexplored. This study aims to validate AK for upper-limb motion tracking against a gold-standard optoelectronic system under optimal and suboptimal conditions. Sixteen healthy adults performed ten upper body motor tasks in three scenarios: optimal setup, seated posture with table occlusion, and increased camera distance. Joint angles were compared using normalized Root Mean Squared Error (nRMSE) and Pearson’s correlation coefficient. Performance Indicators (PIs) including Range of Motion (ROM), smoothness, and Time to Peak Velocity (TTPV) were also evaluated. AK accurately captured movements performed within the camera plane, with median nRMSE below 20% in optimal conditions and no significant degradation in suboptimal setups. In contrast, movements occurring on planes perpendicular to the camera were poorly captured. ROM estimation was acceptable and highly reproducible, while TTPV showed moderate-to-poor reliability and smoothness deviated substantially from the reference system. These findings suggest that careful attention to Kinect positioning is essential to ensure effective acquisitions, even in suboptimal scenarios. Future research should evaluate AK validity in clinical populations and explore the effects of system interference in multi-device setups. Full article

Karst rocky desertification (KRD) is a critical abiotic stressor that compromises Rosa roxburghii Tratt fruit quality, yet its underlying physiological and ecological pathways remain poorly understood. This study aims to bridge this knowledge gap by elucidating how KRD-driven soil C:N:P:K stoichiometric shifts indirectly affect fruit quality (vitamin C and fructose) by disrupting fruit internal elemental balance. We characterized soil nutrient dynamics and evaluated fruit quality along the natural rocky desertification gradient (RDG) in Guizhou, China. Mantel tests and structural equation modeling (SEM) were applied to identify primary predictors and quantify integrated pathways. With increasing desertification, total organic carbon (TOC), total nitrogen (TN), and soil C:P ratio (C:P) increased monotonically, while total phosphorus (TP) remained at a low concentration without significant change. Available phosphorus (AP) and available potassium (AK) followed a U-shaped trend, reaching their minimum under moderate desertification, whereas total potassium (TK) peaked at this stage before declining. Correspondingly, fruit vitamin C (FVC) and fruit fructose (FF) exhibited a non-linear pattern, first increasing under light stress, then decreasing under moderate stress, and finally rebounding under severe desertification, which is consistent with the nonlinear response pattern of fruit C:P ratio (FC:FP) reported for the same desertification stages. The SEM revealed a dual-pathway mechanism: KRD directly enhanced FVC (β = 0.69, p < 0.001), while KRD and soil properties enhanced FF (β = 0.39 and 0.64, respectively, p < 0.01). KRD also indirectly lowered FVC and FF through a sequential nutrient cascade that promoted soil nutrients (Soil, β = 0.81–0.82, p < 0.001), which triggered negative effects particularly via soil stoichiometry (SS, |β| = 0.76–0.91, p < 0.001), with a modest additional contribution from fruit stoichiometry (FS, |β| ≈ 0.27, p < 0.05). This suggests that KRD influences fruit quality via a soil–plant network mediated by soil P-limitation and K-dynamics. Balanced P and K management may, therefore, be critical for maintaining fruit quality and ecological restoration in karst ecosystems. Full article

Vermicomposting is an eco-friendly biotechnology for organic waste valorization. As the primary product of earthworm biotransformation, vermicompost is a high-value bio-organic fertilizer abundant in diverse biologically active components. To date, most studies have focused on quality variation during the earthworm transformation process, while research on quality variations in the resulting vermicompost fertilizer during long-term storage remains scarce. To explore the shelf-life of vermicompost fertilizer and its key influencing indicators, this study investigated the changes in quality indicators in sealed-packaged vermicompost over a 180-day period using two typical vermicompost, namely cattle manure vermicompost (CM) and straw-amended cattle manure vermicompost (CMS). The temporal dynamics of physicochemical properties, nutrient contents, humification indices, enzyme activities, and microbial communities were monitored. The vermicompost quality was evaluated, and core quality drivers were identified using an integrated principal component analysis-partial least squares (PCA-PLS) approach. The results indicated that moisture content (MC), total organic carbon (TOC), and total nitrogen (TN) declined progressively, whereas available phosphorus (AP) and available potassium (AK) peaked at day 150 and day 120, respectively, and the humification rate (HR) increased by 2.6–4.0-fold. Bacterial diversity and relative abundance slightly decreased, accompanied by taxonomic differentiation, whereas fungal communities maintained stable diversity. Most enzyme activities, including urease, phosphatase, catalase, and dehydrogenase, reached their maxima at day 120. Comprehensive quality scores peaked at day 150, with a marked decline observed by day 180. The recommended shelf-life of vermicompost fertilizer is 150 days. The key quality determinants include TN, electrical conductivity (EC), pH, actinomycete abundance, TOC, TP, bacterial abundance, AP, AK, and HR. These findings provide theoretical support and references for the storage management and quality control of commercial vermicompost products in practice. Full article