Search Results (39,695)

To address the issues of high cutting temperatures and severe tool wear during titanium alloy machining, this study proposes a hybrid surface modification strategy combining micro-textures and multicomponent titanium nitride (TiN)-based coatings on cemented carbide tools. Using YG8 cemented carbide as the substrate, micro-dimple textures were fabricated by fiber laser, and three coatings with different architectures (TiAlSiN, TiSiN/TiAlN, and TiSiN/TiAlSiN/TiAlN) were deposited via multi-arc ion plating technology. Based on a two-factor (texture diameter and texture spacing) and three-level orthogonal experiment, the evolution behaviors of surface morphology, phase composition, and mechanical properties of the textured multicomponent TiN-based coatings were systematically characterized and comparatively analyzed. The results reveal that: compared to the monolithic-structured TiAlSiN coating, the TiSiN/TiAlSiN/TiAlN and TiSiN/TiAlN composite coatings with multilayered composite structures can effectively relieve the residual stress inside the film–substrate system, and significantly suppress the phenomena of coating cracking and localized spallation caused by irregular protrusions of the recast layer at the micro-texture edges. X-ray diffraction (XRD) and crystallite size analyses indicate that the amorphous Si₃N₄ phase promoted by the Si element in the composite coatings effectively impedes the growth of TiN columnar crystals, achieving significant grain refinement. Mechanical property tests confirm that the existence of multicomponent composite interfaces effectively hinders dislocation movement. Among them, the textured TiSiN/TiAlSiN/TiAlN composite coating exhibits the optimal comprehensive performance; its microhardness, nanohardness, and H/E ratio (characterizing the resistance to plastic deformation) are increased by 17.94%, 8%, and approximately 45%, respectively, compared to those of the textured TiAlSiN coating. This study deeply elucidates the synergistic strengthening and toughening mechanisms between micro-texture parameters and the internal structures of the coatings, providing important theoretical guidance and experimental data support for the surface design of long-lifespan tools oriented towards the high-efficiency machining of titanium alloys. Full article

This paper presents a holistic development model for South African schools that aims to ensure inclusive and equitable quality education and promote lifelong learning opportunities for all, as defined by the United Nation’s Sustainable Development Goal 4: Quality Education, by 2030. It addresses critical gaps in private secondary schools, including unclear performance objectives, inadequate monitoring, and limited data-driven decision-making. To meet these needs, the study proposes a new performance management model based on Kaplan and Norton’s balanced scorecard framework, combining four perspectives: Students, Academic excellence, Learning and growth, and Resources. Using a positivist approach, the model was validated by confirmatory factor analysis of 244 respondents across 12 private schools in Durban. The Comparative Fit Index, Normed Fit Index, and Tucker–Lewis Index confirmed its structural validity, while the Root Mean Square of Error Approximation indicated excellent absolute fit. Several intercorrelations emerged within the Learning and growth perspective, particularly regarding staff respect for students and their value to students. Implementation revealed an overall satisfactory performance rating of 3.85 on a 5-point scale. The Student perspective scored lowest (3.39), highlighting inadequate student preparation as a key issue, with learners’ pre-class reading of material scoring just 2.81. These findings underscore the model’s utility in identifying areas for improvement, particularly in student engagement, academic excellence, and organisational culture within the Learning and Growth dimension. Full article

Background: Growth hormone deficiency (GHD) in childhood impairs linear growth and may affect body composition, metabolism, and quality of life; recombinant human growth hormone (rhGH) therapy improves outcomes, but response is highly variable, especially in idiopathic GHD (IGHD). Objective: To summarize current evidence on predictors of growth response to rhGH therapy in children with IGHD, focusing on clinical, biochemical, and treatment-related determinants. Methods: This is a narrative review dealing with studies assessing clinical, auxological, biochemical and treatment-associated factors that may influence response to rhGH in IGHD. Results: Early treatment initiation, baseline short stature, prepubertal status, and higher early height growth velocity are strong clinical predictors; biochemical markers, including GH peak, IGF-1, and IGFBP-3, provide complementary information. Modifiable factors such as GH dose, adherence to therapy, and therapy duration also influence outcomes. Integrated predictive models improve accuracy but require further validation. Conclusions: Growth response to rhGH in IGHD is multifactorial and could be individualized: early identification of suboptimal responders and personalized treatment strategies that integrate clinical, biochemical, and treatment-related data may optimize the final outcome. Future research studies should focus on validated predictive models incorporating genetic and molecular markers. Full article

The Changbai Mountain–Liaodong region is a crucial component of the global black soil belt in Northeast China and a significant national grain production base. However, like many high-latitude agricultural regions worldwide, it faces persistent challenges during the spring sowing period, including low soil temperatures and excessive moisture. Therefore, developing region-specific, effective methods of reducing soil moisture and increasing temperature while improving soil fertility is essential for improving agricultural productivity. To this aim, a field experiment was conducted with two factors: a main plot subjected to ridge tillage (RT) and flat tillage (FT) and subplots with biochar (BC) and straw (ST) amendments. A subplot with no amendment (CK) was used as a control. During maize growth, the daily soil temperature and moisture were monitored, and the soil water evaporation rates and physical structure, as well as the maize yield performance, were evaluated. The results showed that biochar and straw application significantly decreased the soil monthly water content by 1.69–2.22% (p < 0.05) in the surface soil layer (0–15 cm) from May to June, with a more pronounced effect under RT. In contrast, biochar application increased soil moisture and water storage from July to September, indicating that the influence of biochar on soil moisture depends on time and field aging processes. Biochar amendment raised the soil maximum temperature by 0.32–0.79 °C in the top 0–15 cm layer, while straw incorporation decreased the minimum soil temperature by 0.11–0.52 °C. The increase in soil temperature was primarily due to the biochar’s darker color, which facilitated solar radiation absorption, while the decrease in soil temperature was caused by the “Wind Leakage Effect” induced by the large particle size of the straw. Biochar and straw incorporation effectively enhanced maize dry matter accumulation by an average of 15.8% and 8.2%, respectively, and grain yield by 13.0% and 7.8%, respectively. Correlation analysis indicates that these increments are primarily due to enhanced soil moisture and available N content during the middle to late stages of maize growth. Therefore, the integration of straw and biochar with high-ridge cultivation is an effective strategy for excessive moisture reduction and warming in spring soil and it also contributes positively to maize yield. Full article

The rapid growth of artificial intelligence (AI) workloads and data center infrastructure is driving a surge in electricity demand, underscoring the need for robust metrics to evaluate energy generation and storage strategies. This study introduces the Bring Your Own Battery (BYOBattery) metric, a region-specific, temporally resolved indicator designed to quantify the ideal energy storage capacity required to mitigate generation-demand mismatches. The BYOBattery metric is computed as the minimum ideal battery storage required to eliminate generation-demand imbalances over a given time window, and is extended to incorporate curtailment via a convex optimization formulation to better manage peak generation and storage requirements. We applied the BYOBattery metric to wind, solar, and nuclear generation technologies across three major U.S. grid regions: the California Independent System Operator (CAISO), the Electric Reliability Council of Texas (ERCOT), and the Pennsylvania–New Jersey–Maryland Interconnection (PJM), using operational data from 2021 to 2024. Key findings are: (1) nuclear consistently requires the least storage in order to meet demand (i.e., one equivalent load hour compared with 10–25 h for wind and solar); (2) wind storage requirements decrease with increased capacity, whereas solar necessitates consistent levels of storage; and (3) the 30-year non-discounted cost per kWh for nuclear ($0.10/kWh) is substantially lower than that of wind or solar by a factor of 1–4 across all studied region. The BYOBattery metric enables comparative benchmarking of generation technologies under dynamic demand conditions and supports cost-informed planning for energy systems. This work contributes a reproducible, interpretable, and computationally efficient tool for energy system analyses and broader performance evaluations. Full article

Trees in arid mountainous forests adapt to seasonal water variability through dynamic eco-physiological adjustments. This study investigated the spatiotemporal dynamics and environmental drivers of such adaptations in Picea schrenkiana Fisch. et Mey, a keystone conifer in China’s Tianshan Mountains. We monitored key indicators—including osmoregulatory substances, antioxidant enzyme activities, and stoichiometric traits—across three regions (eastern, central, western) and three seasons (spring, summer, autumn) during the 2023 growing season. The results revealed significant seasonal shifts in all the measured traits (p < 0.05). Spring was characterized by high carbon allocation toward soluble sugars and starch, supporting growth; summer triggered elevated antioxidant enzyme activities to mitigate oxidative stress; and autumn favored nitrogen accumulation and proline synthesis, indicating preparatory storage for winter. Soil factors were primarily positively associated with antioxidant enzyme activity (path coefficient = 0.51; p < 0.001), whereas microenvironmental factors were more complex and often negatively correlated. The partial least squares path model confirmed that osmoregulatory substances centrally link stoichiometric adjustments with antioxidant defense, revealing an integrated physiological strategy. These findings elucidate the mechanism underlying the resilience of P. schrenkiana in arid highlands and provide a framework for its conservation under environmental change. Full article

Background: While the prognostic and predictive value of tumor cell–derived features such as grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and Ki67 index is well established in breast cancer, less is known about the prognostic role of tumor stroma. This study aimed to evaluate stromal parameters in HER2-positive breast cancer patients treated with adjuvant trastuzumab. Material and methods: The study included 224 patients (T ≥ 1, N ≥ 0, M0) who underwent radical treatment followed by adjuvant chemotherapy, hormone therapy (if ER/PR-positive), and trastuzumab. The following histological and immunohistochemical parameters were analyzed: stroma type, tumor-infiltrating lymphocytes (TILs), eosinophils, neutrophils, central area of fibrosis, necrosis, and programmed cell death protein ligand 1 (PD-L1) expression in tumor and stromal cells. Results: Low TILs percentage (≤50%) was associated with lower tumor grade (G2) (p = 0.013) and ER/PR positivity (p = 0.001). Tumors lacking PD-L1 expression had a lower percentage of TILs (p < 0.001), less frequently exhibited tumor-associated neutrophilia (p = 0.019), and more often presented with desmoplastic stroma (p < 0.001). The following parameters were associated with prognosis: TILs percentage, stroma type, and PD-L1 expression. High TILs percentage (>50%) was an independent positive prognostic factor. Conclusions: In patients with HER2-positive breast cancer treated with adjuvant trastuzumab, the percentage of TILs, stroma type, and PD-L1 expression are prognostically relevant. Specifically, a TILs percentage >50% independently predicts favorable outcomes. Routine evaluation of stromal features may provide additional prognostic information and support treatment planning. Full article

The homeodomain-leucine zipper (HD-Zip) transcription factor family is conserved in land plants and is critical for regulating growth, development, and stress responses. Flax (Linum usitatissimum L.) is an economically valuable dual-purpose crop valued for its high nutrition and notable drought tolerance; however, its HD-Zip gene family has not been systematically characterized. In this study, a comprehensive genome-wide analysis was performed to identify and characterize the HD-Zip family in flax. A total of 34 LuHD-Zip genes were identified, which were unevenly distributed across 15 chromosomes and exhibited substantial variation in physicochemical properties. The encoded proteins ranged from 200 to 372 amino acids in length, with molecular weights of 22.7–40.3 kDa and theoretical isoelectric points (pI) of 4.49–9.46. All LuHD-Zip proteins were predicted to be hydrophilic and localized to the nucleus. Phylogenetic analysis divided these proteins into two major subfamilies (Group 1 and Group 2), a classification strongly supported by conserved gene structures and motif compositions, implying potential functional redundancy within each group. Gene duplication analysis revealed that segmental duplication events (29 pairs) were the primary drivers of family expansion. Comparative syntenic analysis further indicated that the LuHD-Zip gene family has remained relatively conserved throughout evolution. Promoter cis-element analysis identified multiple regulatory elements associated with hormone signaling and abiotic stress responses, suggesting complex transcriptional control in response to environmental stimuli. Expression profiling via quantitative real-time PCR (qRT-PCR) demonstrated that LuHD-Zip genes exhibit tissue-specific expression patterns and are differentially regulated by various phytohormone treatments and abiotic stresses. This study provides the first genome-wide characterization of the HD-Zip gene family in flax, offering valuable insights into its evolution and potential functions. These findings establish a solid foundation for future functional investigations of the LuHD-Zip gene family. Full article

The block-and-lock strategy aims to achieve a functional cure for human immunodeficiency virus type 1 (HIV-1) infection by enforcing durable, drug-independent silencing of proviral transcription. Several latency-promoting agents have been described that effectively limit viral reactivation in vitro or in animal models. However, most approaches induce only partial or reversible transcriptional repression and have not yet been translated into safe and effective clinical interventions. This review summarizes the molecular mechanisms underlying block-and-lock strategies and critically evaluates the limitations of current candidate compounds. We highlight recent advances in understanding HIV-1 integration site selection, focusing on the roles of lens epithelium-derived growth factor p75 (LEDGF/p75) and cleavage and polyadenylation specificity factor subunit 6 (CPSF6) in directing proviral integration toward gene-dense, transcriptionally active chromatin. Pharmacological disruption of the LEDGF/p75–integrase interaction by LEDGF/p75 inhibitors (LEDGINs) redirects proviral integration toward less transcriptionally active genomic regions that are more resistant to reactivation. Recent tandem knockout experiments, however, demonstrate that CPSF6 plays a dominant role in guiding HIV-1 integration toward gene-dense, transcriptionally active chromatin. LEDGIN treatment has been linked to the preferential targeting of proviruses to heterochromatin-rich regions within the nuclear interior. By contrast, CPSF6 knockout redirects integration toward peripheral heterochromatin, especially lamina-associated domains (LADs), genomic regions typically exhibiting stronger and more stable transcriptional repression than interior heterochromatin. These findings suggest that therapeutic modulation of CPSF6 may exert a more profound and durable effect on proviral silencing within a block-and-lock framework. Nevertheless, complete CPSF6 ablation is associated with severe cellular toxicity. The challenges associated with CPSF6-related adverse effects and potential strategies to overcome these limitations are discussed. Full article

To improve nitrogen (N) fertilizer management in vineyards and support sustainable production, we conducted field experiments in 2021–2022 to evaluate the effects of reduced N fertilization combined with organic fertilizer (OF) on vine growth, fruit quality, soil fertility, and economic returns in Shine Muscat grapes. Six treatments were established: conventional fertilization (CF), four reduced-N treatments combined with OF (0.9N + OF to 0.6N + OF; i.e., 10–40% N reduction), and a blank control (CK). Yield was significantly increased under 0.8N + OF (18.2% in 2021; 96.0% in 2022) and 0.7N + OF (10.8% in 2021; 47.9% in 2022), with 0.8N + OF also delivering the highest economic returns. Fruit quality analysis showed that 0.8N + OF consistently increased total sugar and the sugar–acid ratio, and improved vitamin C content. Substitution ratios >40% led to a decline in economic benefits. Path analysis indicated that vertical diameter and single-berry weight exerted significant positive effects on total yield. OF substitution also improved fruit quality. Soil available nutrients (N, P, and K) and organic matter were primary factors influencing yield; potassium was the key factor regulating sugar accumulation, with the strongest effect on improving flavor coordination. Reducing N by 20–30% combined with OF (particularly the 0.8N + OF treatment) synergistically enhanced photosynthetic efficiency, N utilization, yield and quality, and soil fertility, representing the optimal fertilization strategy. Full article

Diabetic retinopathy is increasingly recognized as a neurovascular disorder rather than a purely vascular disease; however, therapeutic strategies targeting retinal neurodegeneration remain limited. In this study, we investigated the protective effects of norrin against hyperglycemia-induced retinal neurodegeneration and elucidated its underlying molecular mechanisms in diabetic mice. We found that retinal neurodegeneration may precede microvascular leakage in diabetic retinas. Norrin, which is expressed in the inner retina, was significantly downregulated under diabetic conditions. Intravitreal supplementation of norrin markedly attenuated hyperglycemia-induced neurodegenerative processes, leading to retinal ganglion cell (RGC) apoptosis, including oxidative stress, inflammation, and neuropathological alterations such as reactive gliosis, glutamate excitotoxicity, and synaptic dysfunction. Norrin also reduced hyperglycemia-induced microvascular leakage and RGC apoptosis by normalizing vascular endothelial growth factor (VEGF) overexpression and restoring pigment epithelium-derived factor (PEDF) levels. Notably, PEDF upregulated by norrin effectively suppressed neurodegenerative processes induced by hyperglycemia or VEGF, thereby preserving RGC function. These findings identify norrin as a critical modulator of hyperglycemia-induced retinal neurodegeneration through restoration of the VEGF–PEDF balance. Our results highlight norrin as a potential therapeutic target for early neurodegenerative changes in diabetic retinopathy. Full article

Epidermal growth factor receptor (EGFR)-kinase domain duplication (KDD) represents an atypical mutation distinct from classical EGFR mutations in lung adenocarcinoma (LUAD). Although first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity in EGFR-KDD, the mechanisms of acquired resistance in this setting remain poorly characterized. Herein, we present a LUAD patient with EGFR-KDD who achieved a sustained initial response to afatinib lasting 67 months before developing acquired resistance. Re-biopsy with next-generation sequencing (NGS) uncovered EGFR T790M, accompanied by EGFR amplification and EGFR M766T. The patient was switched to firmonertinib, with subsequent tumor regression. We reviewed published EGFR-KDD cases that had both acquired resistance to first- or second-generation EGFR-TKIs and corresponding repeat biopsy findings. Five of the eleven cases harbored EGFR T790M, yielding a prevalence of 45%, which is similar to that seen in classical EGFR mutations. This case suggests that EGFR T790M mediates acquired resistance to first- and second-generation EGFR-TKIs in EGFR-KDD, mirroring the resistance pattern observed in classical EGFR mutations. Full article

Using panel data from 278 Chinese prefecture-level cities during 2011–2019, this study employs two-way fixed effects and instrumental variable (2SLS) models to investigate how the distinct dimensions of digital financial inclusion (DFI)—coverage breadth, usage depth, and digitisation level—affect urban economic growth. The results reveal substantial heterogeneity across these DFI dimensions. The expansion of coverage breadth significantly and robustly promotes city-level economic growth. In contrast, greater usage depth exerts a negative effect, possibly due to regulatory lags in internet credit and insurance that intensify financial risks. The digitisation level shows a positive but statistically insignificant impact, indicating that digital infrastructure has not yet been fully transformed into growth-enhancing productivity. Furthermore, the regional heterogeneity analysis reveals a stark divergence: DFI acts as a crucial growth engine in the financially underserved central and western regions, whereas excessive financialisation has exerted a crowding-out effect in eastern cities. These findings suggest that policy efforts should prioritise broadening DFI coverage while strengthening the regulation of usage-related activities, thereby balancing financial innovation with systemic stability. Full article

Aspergillus flavus is a globally distributed filamentous fungus of major agricultural and medical importance, capable of producing carcinogenic aflatoxins and forming two specialized developmental structures, conidia and sclerotia. While the molecular framework governing conidiation has been well characterized in Aspergillus nidulans, the corresponding mechanisms in A. flavus remain somewhat unelucidated. In this study, we identified and functionally characterized AfldrnA, a gene encoding a basic helix–loop–helix (bHLH) transcription factor. Targeted deletion of AfldrnA resulted in an aconidial phenotype accompanied by a significant increase in sclerotia formation, whereas complementation with the intact AfldrnA gene restored conidiation and reduced sclerotia development. Phenotypic assays revealed that the ΔAfldrnA mutant exhibited normal vegetative growth, unchanged antifungal susceptibility, and unaffected aflatoxin B₁ production, indicating that AfldrnA primarily regulates developmental rather than metabolic differentiation. Additionally, observed differences between standard and dark incubation conditions suggest that AfldrnA may be involved in environmentally responsive regulation of fungal development. Overall, this study identifies AfldrnA as a pivotal transcriptional regulator essential for coordinating conidiation and sclerotia formation in A. flavus, providing new insights into the genetic and environmental regulation of fungal developmental programs. Full article

Purpose: Cannabidiol (CBD) is a primary bioactive, non-intoxicating cannabinoid found in the cannabis plant. Studies have shown that CBD causes anticancer activity by inhibiting the expression of growth factors and inducing apoptosis, leading to cell cycle arrest. In this study, we aimed to determine how CBD influences the expression of genes that affect cancer pathways in doxorubicin-sensitive (MCF-7) and doxorubicin-resistant (MCF-7/Adr) breast cancer cells. Materials and Methods: IC₅₀ concentrations of CBD in MCF-7 and MCF-7/Adr cell lines were determined by the MTT cell cytotoxicity assay. RNA isolation and subsequent cDNA synthesis were performed for qPCR experiments with the determined IC₅₀ values. The effects of CBD on the cell cycle and apoptosis were studied using flow cytometry. IC₅₀ values of CBD were determined in MCF-7 and MCF-7/Adr breast cancer cell lines at eight different concentrations and at three different incubation periods (24 h, 48 h, and 72 h) with different doses. RT-qPCR was used to investigate the molecular mechanisms underlying the expression of genes involved in cancer pathway analysis. Results: Treatment with CBD at concentrations of 17.57 μM (MCF-7) and 11.41 μM (MCF-7/Adr) for 48 h decreased colony formation, induced apoptosis, and inhibited cell invasion in both cell lines. In addition, we observed significant alterations of angiogenesis, apoptosis, cell cycle, cellular senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, metabolism, telomeres, and telomerase in both cell lines. Conclusions: Our research indicates that CBD could be an effective natural bioactive compound for breast cancer treatment, inhibiting tumor cell proliferation and inducing apoptosis. Full article