Search Results (15,425)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have proven their favorable cardiovascular and nephroprotective benefits in large randomized-controlled trials (RCTs). Given that older adults constitute a substantial part of patients with type 2 diabetes mellitus (T2DM), heart failure (HF), and chronic kidney disease (CKD), they are the primary target population for SGLT2 inhibitor therapy. However, their representation in clinical trials remains low and it does not reflect the real-life heterogeneity of this group of patients. As chronological age alone does not adequately reflect the biological age, it is important to evaluate older adults using a multidimensional approach, particularly with regard to frailty. This review aims to summarize and critically appraise the available evidence regarding the efficacy of SGLT2 inhibitors in older and frail adults, with a focus on age-specific outcomes, such as cognitive outcomes, risk of sarcopenia, functional activity and current gaps in evidence related to frailty. Full article

Urban areas require context-specific bioenergy solutions to advance toward circular and sustainable energy systems. In Bogotá, urban pruning and grass-cutting residues constitute a relatively stable biomass stream; however, the absence of district-scale valorization infrastructure leads to their direct disposal in landfill. This study develops and applies a GIS-based planning methodology to support the territorial design of a small-scale anaerobic digestion plant using urban green waste. In this study, “small-scale” is understood as an early-stage urban facility concept compatible with the available pruning stream of approximately 1200–1300 t/month of valorizable biomass, corresponding only to an order-of-magnitude energy range of a few hundred kW${}_e$/kW${}_t$, rather than to a final engineering design. The approach integrates official geospatial data with logistical, environmental, and institutional criteria to characterize biomass availability and evaluate location alternatives under real urban constraints. A continuous location model based on the Weber problem is first applied to estimate a theoretical lower bound of spatial effort, using public schools weighted by enrollment as a proxy for sensitive urban demand. Subsequently, a GIS-assisted Analytic Hierarchy Process (AHP) is implemented to incorporate environmental exclusions, territorial compatibility, and the operational structure of exclusive waste service areas. Results show that the optimal geometric location diverges from the territorially feasible alternative once environmental restrictions and biomass supply coherence are explicitly considered. The findings highlight that urban bioenergy infrastructure planning is governed less by pure spatial efficiency than by the integration of supply, demand, and institutional constraints. The proposed methodology provides a reproducible decision-support tool for urban bioenergy planning and contributes to sustainable waste management, circular economy strategies, and local energy resilience in cities of the Global South. Full article

The present study investigated the detection performance of the YOLOv8s, YOLO11s, and YOLO12s models, implemented within convolutional neural network architectures, for identifying floricane raspberry (Rubus idaeus L.) shrubs using RGB imagery and multispectral data acquired in the near-infrared, red-edge, red, and green spectral bands with a DJI Mavic 3 Multispectral drone. Model training and validation were conducted to evaluate both within-modality detection performance and cross-modality transferability. Under all training scenarios, the YOLO-based detectors reached near-saturated accuracy levels. However, cross-domain assessments demonstrated substantial variability depending on the spectral configuration of the input imagery. Overall, the combination of UAV-based multispectral sensing with convolutional neural network detection frameworks establishes a technological basis for automated shrub monitoring and constitutes a meaningful advancement toward intelligent raspberry production systems. This integration further creates new prospects for the technological development of cultivation practices for this crop within the rapidly evolving landscape of artificial intelligence-driven agriculture. Full article

BASIC PENTACYSTEINE (BPC) transcription factors are plant-specific and play crucial roles in regulating plant development and responses to abiotic stresses. However, the genomic characteristics of the BPC gene family in Brassica juncea and its regulatory mechanisms in response to light and salicylic acid remain poorly understood. In this study, we identified 25 BjuBPC genes in the B. juncea genome using bioinformatic approaches. All BjuBPC proteins were predicted to localize exclusively to the nucleus, with their distribution scattered across 14 chromosomes of B. juncea. Phylogenetic analysis classified these BjuBPC genes into three subfamilies (A, B, and C). The 25 BjuBPC genes showed strong collinearity with BPC orthologs from Arabidopsis thaliana, Brassica rapa, and Brassica nigra, and members of the same subfamily shared highly conserved exon–intron architectures and motif compositions, and a highly conserved canonical GAGA DNA-binding domain. Expression profiling across tissues revealed both tissue-specific and constitutive expression patterns among BjuBPC members. Subsequent expression analyses under four light qualities and exogenous salicylic acid treatment demonstrated that BjuBPC1, BjuBPC9, and BjuBPC24 were specifically responsive to both light and salicylic acid signals, with markedly strong induction by blue light. These findings provide valuable insights for future functional characterization of BjuBPC genes and enhance our understanding of their biological roles in B. juncea. Full article

The compliant discharge of landfill leachate constitutes a pivotal factor for the effective implementation of integrated water resource management. Aged landfill leachate exhibits complex composition and an imbalanced carbon-to-nitrogen ratio. Electrocatalytic oxidation technology, as an efficient advanced oxidation process, demonstrates promising application potential. This study employed Ti/RuO₂–IrO₂ Anodes for the electrocatalytic oxidation treatment of aged landfill leachate. The removal efficiencies and variation patterns of chemical oxygen demand (COD), ammonia nitrogen, and total nitrogen at different current densities and reaction times were systematically investigated, along with an analysis of energy consumption and current efficiency. The degradation and transformation processes of organic matter were elucidated using Three-dimensional Excitation–Emission Matrix (EEM) Spectra. Fresh anodes and those used for 1000 h were characterized by scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) to elucidate their failure mechanisms. The results demonstrate that electrocatalytic oxidation achieves efficient pollutant removal. At a current density of 1000 A/m² and a reaction time of 30 min, the effluent concentrations of ammonia nitrogen and total nitrogen satisfied the discharge standards, while COD complied with emission requirements after 60 min. The pollutant removal efficiencies were positively correlated with current density and reaction time. EEM analysis revealed that the electrocatalytic process effectively disrupts the structure of macromolecular organic matter, degrading it into smaller molecules and eventually achieving complete mineralization. Electrode characterization identified titanium substrate corrosion due to coating cracks and coating detachment as the primary causes of electrode failure. This study confirms the effectiveness of electrocatalytic oxidation technology for treating aged landfill leachate, and provides a theoretical foundation and technical support for its practical engineering application. The technology exhibits considerable theoretical significance and promising application potential in the treatment of landfill leachate. Full article

Against the backdrop of population aging, community parks are important spaces for older adults’ daily activities, and perceived safety plays a key role in shaping their use and spatial satisfaction. This study selected six typical community parks in central Beijing, constructed an indicator system for safety perception needs, and applied an analytical KANO–IPA (Integrated Kano and Importance-Performance Analysis) approach to identify the demand attributes and optimization priorities of safety elements. The results reveal a clear hierarchy in older adults’ safety perception needs. Basic environmental and facility safety factors, such as pavement conditions and facility reliability, function as must-be needs. Elements related to spatial visibility, circulation, lighting, and wayfinding act as one-dimensional needs that steadily influence satisfaction, whereas features including natural surveillance, spatial enclosure, and activity atmosphere mainly enhance spatial experience as attractive needs. Priority analysis further indicates that circulation conditions and facility safety constitute the most critical aspects for improvement. Overall, older adults’ safety perception in community parks results from the combined effects of multiple spatial factors. Hierarchical spatial optimization can enhance user experience and improve resource allocation efficiency. The findings provide theoretical support and decision-making guidance for safety-oriented planning and age-friendly renewal of urban community parks in aging societies. Full article

The objective of this research was to apply morphometric and chemometric techniques to analyze the influence of climate and soil type on the morphological, proximate, and fatty acid fingerprints of moringa (Moringa oleifera Lam.) seeds cultivated in different regions of Mexico. Seeds were collected from the states of Chiapas, Michoacán, Nuevo León, Oaxaca, Veracruz, and Yucatán. The morphological traits of the seeds were evaluated, while the proximate composition and fatty acid profiles of the seed flours were analyzed using gas chromatography–mass spectrometry (GC–MS). Data were assessed through analysis of variance (ANOVA) and linear discriminant analysis to develop their fingerprint profiles. The results showed that the morphological variables that constituted the climate-based morphological fingerprint were seed length, width, seed weight, and kernel weight, whereas for the soil type-based fingerprint, only seed length was significant. Regarding the proximate chemical composition, all variables (fat, ash, moisture, and protein), except fiber content, were influenced by both climate and soil type, forming the proximate chemical fingerprint. The fatty acid fingerprint consisted of 21 compounds, with oleic, behenic, stearic, palmitic, and arachidic acids present in the highest concentrations. The fingerprints obtained from the different determinations were confirmed through cross-validation values exceeding 50%, according to the linear discriminant analysis validation technique. The fatty acid and proximate composition determinations showed the highest classification values (83–100%) and contributed most significantly to ensuring the fingerprinting of moringa seeds cultivated in Mexico. Full article

This paper examines how Dushyant Kumar’s collection, sāye meṅ dhūp (lit. Sunlight in the Shadows), reinvented the classical ġhazal genre as a vernacular weapon of anti-authoritarian dissent—not by abandoning ambiguity, but by recalibrating it under conditions of constraint—during India’s Emergency. This study argues that Kumar’s work constitutes a radical departure from the genre’s traditional emphasis on the abstract longing of the lover for the beloved and other tropes which are peculiar to writing ġhazal in the Perso-Urdu world. Instead, Kumar systematically repurposed its conventions—its ambiguity, its metaphors of the beloved and the garden, its themes of sacrifice—to mount a sharp polemic against Indira Gandhi’s regime. Through an analysis of ġhazal-s selected for their range of polemical strategies—from direct satire and political allegory to the recasting of traditional themes like martyrdom—this paper demonstrates how Kumar’s conscious use of a blended Hindi–Urdu vernacular was central to his political project. By writing in “the language I speak,” he dragged the elite ġhazal into the public square, transforming it into a medium for articulating collective disillusionment, resistance, and a scathing critique of a democracy in crisis. Kumar’s work thus stands as a testament to the ġhazal’s potent, and often overlooked, capacity for explicit political engagement. Full article

In this study, we explore how to balance the preservation of the original appearance of ancient villages with their development within the framework of World Heritage protection. We applied resilience theory and constructed a simple checklist, taking cultural ecosystem services into consideration, and selected the Zuojiang Huashan Rock Art Heritage Area in China for field investigation, as well as conducted in-depth interviews, the distribution of short questionnaires, and two rounds of Delphi surveys. This comprehensive approach enabled us to discover the key cultural ecosystem services that villagers rely on for their livelihoods. Then, we tracked how these services enhanced buffering capacity, helped people self-organize, and promoted adaptive learning. The results show that cultural ecosystem services constitute the core framework of the social–ecological resilience of the villages. The quantity and combination of the services directly determine the resilience score, and the resilience of villages within the heritage area shows significant spatial differentiation. High-resilience villages have diverse and mutually reinforcing cultural ecosystem services and local community rules, while low-resilience villages face service loss, weakened social connections, and single development options. Through this study, we aim to further enrich the cultural connotation of resilience theory, provide a practical assessment tool for practitioners of the method, and offer practical guidance and suggestions for transforming heritage protection from static protection to a dynamic, vibrant system that promotes vitality and resilience in practice. Full article

This study investigated the impact of the pretreatment of pea plants (Pisum sativum L. Ran 1) for five days by three times higher light intensity (360 μmol m⁻² s⁻¹) than the intensity for their cultivation (120 μmol m⁻² s⁻¹) on the photosynthetic apparatus’s ability to withstand moderately high temperatures. Photosystem II (PSII) performance was assessed by pulse amplitude-modulated (PAM) fluorometry—evaluation of F_v/F_m, Chl fluorescence decrease ratio—R_Fd, excitation pressure on PSII (1 − qP), non-photochemical quenching (NPQ) analysis, and PsbA (D1) abundance. The redox state of P700 was used to examine photosystem I (PSI), and the redox kinetics of P700 was evaluated as an estimate of cyclic electron flow (CEF). The energy distribution and interaction between the two photosystems were assessed by 77 K chlorophyll fluorescence. Diphenylhexatriene (DPH) fluorescence polarization and PsbS accumulation were followed to estimate alterations in thylakoid membrane characteristics. Our data show that pea plants pretreated with a higher level of light intensity showed higher resistance to temperature increase, maintaining R_Fd values similar to control plants, and the effect of high temperature on PSII excitation pressure (1 − qP) was mitigated. A significant difference between the two groups of plants was observed in terms of quantum yields in both types of non-photochemical quenching, with light pretreated plants showing no change in the energy partitioning ratio while the exposure of non-high light pretreated plants to elevated temperatures led to a more significant increase in quantum yield of constitutive non-photochemical quenching. When plants were exposed to higher temperature, the accumulation of PsbS, induced by high light treatment, was accelerated, and stabilization of thylakoid membrane also occurred. A complex mechanism behind the enhanced tolerance to higher temperature includes the reorganization of membrane pigment–protein complexes, which is regulated by the buildup of PsbS and the accompanying redistribution of excitation energy. Full article

Background and Objectives: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and remains a leading cause of cancer-related mortality worldwide. EGFR-targeted tyrosine kinase inhibitors (TKIs) have substantially improved outcomes in EGFR-mutant NSCLC; however, primary and acquired resistance continues to limit their long-term efficacy. HER3 (receptor tyrosine-protein kinase ErbB3), a member of the ErbB receptor family, has been implicated in TKI resistance through heterodimerization with EGFR and HER2, leading to downstream PI3K/AKT pathway activation. Despite its biological plausibility as a resistance mediator, the clinical significance of HER3 expression as a prognostic and predictive biomarker in EGFR-mutant NSCLC has not been thoroughly characterized in real-world cohorts. Materials and Methods: This retrospective, single-center study included 52 patients diagnosed with EGFR-mutant NSCLC who received TKI therapy at Afyonkarahisar Health Sciences University between January 2011 and September 2023. HER3 protein expression was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumor tissue sections using the Huabio anti-HER3 antibody (clone PD00-44, 1:2000 dilution). Staining in more than 30% of tumor cells was considered HER3-positive; membranous staining intensity was scored on a 1–3 scale. Progression-free survival (PFS1, PFS2) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test. Statistical significance was set at p < 0.05. Results: Of 52 patients (55.8% female; mean age 64.5 years), 59.6% received chemotherapy and 40.4% received an EGFR TKI as first-line treatment; erlotinib constituted 71.2% of targeted therapies. In the first-line TKI group, HER3-negative patients had a numerically longer median PFS1 compared with HER3-positive patients (14.0 vs. 7.1 months; p = 0.285); however, this difference did not reach statistical significance and should be interpreted with caution given the small sample size. In contrast, among patients receiving first-line chemotherapy, HER3 staining status did not meaningfully affect PFS1 (4.1 vs. 2.5 months; p = 0.063). In second-line treatment, HER3-positive patients who received TKI after prior chemotherapy demonstrated a PFS2 comparable to or slightly exceeding that of HER3-negative patients (21.8 vs. 19.8 months; p = 0.49), suggesting that the sequencing of chemotherapy before TKI may attenuate the adverse effect of HER3 positivity. Median OS was 15.1 months in HER3-negative patients and 12.7 months in HER3-positive patients (p = 0.824); this numerical difference of approximately 3 months did not reach statistical significance and should therefore be interpreted cautiously. Among patients receiving TKI in the first line, HER3-positive patients had a shorter median OS than HER3-negative patients (9.6 vs. 14.2 months), whereas those receiving TKI in the second line showed a trend toward longer OS in HER3-positive patients (20.5 vs. 17.2 months). Conclusions: HER3 expression was associated with reduced first-line TKI efficacy in EGFR-mutant NSCLC, suggesting a possible role for HER3 in primary TKI resistance; however, these findings are exploratory and did not reach statistical significance. The observation that HER3-positive patients who received chemotherapy before TKI demonstrated outcomes comparable to HER3-negative patients raises the hypothesis that treatment sequencing may potentially influence the impact of HER3 positivity, though this requires prospective validation before any clinical conclusions can be drawn. These results suggest that HER3 expression may warrant further investigation as a candidate biomarker for treatment sequencing decisions and as a potential therapeutic target in EGFR-mutant NSCLC. Prospective studies evaluating chemotherapy–TKI sequencing and HER3-directed agents such as patritumab deruxtecan (HER3-DXd) in HER3-positive patients are needed to confirm these preliminary observations. Full article

The milpa (a traditional Mesoamerican agricultural system) constitutes a dynamic space with a great diversity of agro-food and sociocultural resources. The objective of this study was to evaluate the milpa’s contribution to food self-sufficiency and to document perceptions of its attributes and cultural significance in San Felipe Tejalápam, Oaxaca. Using a mixed-methods design that included food frequency questionnaires, 24 h dietary recalls (n = 50), and semi-structured interviews (n = 12), the percentage of adequacy (PA) and the symbolic perception of the milpa were analyzed. The results indicate that milpa foods are important for local nutrition, providing significantly higher percentages of adequacy (p ≤ 0.05) for carbohydrates (63.72%), fiber (69.72%), and iron (77.22%). However, the system proved insufficient in energy (42.35%), protein (32.38%), vitamin C (2.69%), vitamin E (0.17%), and potassium (11.14%) compared to external food sources. From a cultural perspective, the milpa was identified as a pillar of community identity. Participants highlighted its culinary properties, health benefits, and its role as a driver of economic and food self-sufficiency. It is concluded that the milpa not only satisfies key nutritional needs but also preserves ancestral knowledge and strengthens the social fabric of the population. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death, yet adequate in vitro models mimicking the tumor immune microenvironment (TIME) are rare. Specifically, the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in modulating interactions between tumor cells and tumor-associated macrophages (TAMs) is not fully understood. We established a 3D multicellular tumor spheroid (MCT) model using murine N-HCC25 cells with CRISPR/Cas9-mediated knockouts of Nrf2 and its negative regulator Kelch-like ECH-associated protein 1 (Keap1), the latter mimicking constitutive activation. N-HCC25 cells were co-cultured with bone marrow-derived macrophages (BMDMs) isolated from wild-type and Nrf2-knockout C57BL/6J mice. We compared co-culture setups (conditioned media, transwell systems, direct contact) using RT-qPCR, flow cytometry, and invasion assays. 3D spheroid systems better preserved stemness than 2D cultures and revealed functional Nrf2-dependent effects such as increased Vegf-α secretion in Keap1-deficient spheroids. Among the different co-cultivation models, the most profound effects were observed in the MCT model. Macrophages successfully integrated into the spheroids and triggered invasive outgrowth, whereas MCTs containing Nrf2-deficient macrophages displayed markedly reduced tumor spheroid growth and lower programmed cell death ligand-1 expression. These findings demonstrate that Nrf2 signaling in macrophages fosters an immunosuppressive and pro-invasive microenvironment. The established MCT model provides a suitable platform to further unravel Nrf2-dependent mechanisms in the HCC TIME. Full article

Amidst global economic volatility and technological disruption, enhancing supply chain efficiency remains critical, yet the fragmented theoretical frameworks, opaque mediation mechanisms, and neglected contextual heterogeneity in understanding how new quality productivity forces (NQPFs) drive this transformation constitute a critical research gap. This study empirically examines NQPF’s impact on supply chain efficiency and its underlying mechanisms, addressing three core problems: first, the lack of a holistic NQPF framework integrating digital, green, and talent dimensions; second, insufficiently explored mediating roles of technological innovation; and third, unaddressed heterogeneity across ownership types, industries, and regions. Using 2012–2022 panel data from Shanghai and Shenzhen A-share listed companies, we employ robustness tests, mediating effect models, and heterogeneity analyses. The results reveal that the NQPF significantly improves supply chain efficiency, primarily through technological innovation—which accounts for 84.6% of the variance—acting via technological innovation, management restructuring, and digital transformation. Crucially, heterogeneity analysis reveals stronger effects in state-owned enterprises, nonhigh-tech industries, and Eastern China, whereas high-tech sectors face integration challenges. Our originality lies in three aspects: integrating the NQPF’s multiple dimensions into a unified theoretical framework; empirically clarifying the “black-box” mediation of innovation; and providing granular evidence for differentiated regional/industrial policies to bolster supply chain resilience. Full article

Mild behavioral impairment (MBI) constitutes a late-life transition state that is associated with an increased risk of cognitive impairment and dementia. Herein, we cross-sectionally describe the MBI construct and its relationship with cognitive status in Mexican-Mestizos (MM) older adults. Participants were classified according to their cognitive and behavioral statuses using tests administered to older adults and their informants. APOE_rs429358/rs7412 variants were genotyped by real-time PCR. Multivariate correlation and Principal Components Analysis (PCA) were used in statistical analysis. A total of 246 participants were included, 56.1% were classified as individuals with NC, 13.0% had subjective cognitive decline, and 30.9% had mild cognitive impairment. A total of 37% (91/246) of participants from all over the cognitive spectrum met the MBI criteria; among this group, APOEε4 homozygosity was associated with two subdomains of the MBI. Subjective cognitive complaint, symptoms of depression, and cognitive decline reported by the informant were associated with an increased risk for MBI (ORs in the range of 4.7–15.89). The first three components of PCA explained 68.0% of the variance of the dataset, including the MBI-checklist total score as a main contributor. Well-known risk factors for dementia also correlated with this PCA. MBI could be a potential marker for cognitive decline in non-demented MM elderly people; however, observed associations should be confirmed in future longitudinal studies. Full article