Search Results (33,657)

Background/Objectives: Chronic traumatic spinal cord injury (SCI) causes persistent neurological deficits for which no clinically effective regenerative therapy is currently available. Mesenchymal stromal/stem cells (MSCs), particularly Wharton’s jelly-derived MSCs (WJ-MSCs), demonstrate immunomodulatory and neurotrophic potential. This phase I/II study evaluated the safety and efficacy of intrathecal allogeneic WJ-MSC administration in individuals with chronic incomplete cervical SCI. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial (NCT05054803, EudraCT 2021-000346-18), 18 participants with chronic (1–5 years post-injury) incomplete cervical SCI (AIS B–D) received two intrathecal injections of WJ-MSCs (0.7–1.3 × 10⁶ viable cells/kg) or a placebo at baseline and 3 months. Seventeen participants completed the 12-month follow-up. Primary outcomes assessed safety, and secondary endpoints included International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor and sensory scores, spasticity, neuropathic pain, functional independence, neurophysiological measures, and quality of life. Results: Intrathecal WJ-MSC administration was safe and well tolerated. Eighty adverse events occurred (placebo: 26; WJ-MSC: 54), predominantly mild or moderate; four severe events were unrelated to treatment. Both groups demonstrated significant within-group improvements in total motor scores at 12 months, with no between-group difference. No treatment effects were observed for sensory scores, electrophysiological measures, functional independence, spasticity, pain, or patient-reported outcomes. Conclusions: In this first randomised, placebo-controlled trial evaluating intrathecal WJ-MSCs in chronic incomplete cervical SCI, WJ-MSC administration demonstrated a favourable safety profile; however, no significant between-group differences were detected relative to the placebo. Given the limited sample size and early-phase design, the efficacy findings should be interpreted cautiously. Future research should explore enhanced cell products, intensified dosing schedules, optimised delivery strategies, early intervention, and multimodal therapeutic combinations. Full article

Nighttime light (NTL), a crucial indicator of human activity intensity, has not been systematically analyzed for its interactive mechanisms with air pollution and climate change. This study first investigates the spatiotemporal evolution of China’s total nighttime light (TNTL) and average nighttime light (ANTL), alongside key indicators of meteorological parameters and air pollution, at the grid scale from 2000 to 2023. We then employ prefecture-level city data and a geographically and temporally weighted regression (GTWR) model to quantify the spatiotemporally heterogeneous associations of temperature (TMP), precipitation (PRE), fine particulate matter (PM_2.5), ozone (O₃), land use (LUL), topography, and socioeconomic factors with NTL. The results indicate that (1) China’s NTL exhibits a significant overall upward trend, with areas of increase or significant increase comprising 92.04% of the total study area. TNTL growth demonstrates regional heterogeneity, expanding by a factor of 4.91 in East China and 2.65 in Northeast China; (2) meteorological and air pollution indicators display spatiotemporal non-stationarity, with the synergistic effect between O₃ and PRE being the strongest; (3) among NTL drivers, LUL contributes most significantly (0.44), followed by TMP (0.14) > PM_2.5 (−0.33 × 10⁻¹) > O₃ (0.17 × 10⁻¹) > PRE (−0.33 × 10⁻⁶); (4) TMP and PRE may primarily influence NTL by altering ecological conditions and nighttime activity patterns. TMP shows a strong positive correlation with NTL in the junction zone of South, East, and Central China, whereas PRE predominantly exerts a negative influence; (5) air pollution exhibits distinct spatiotemporal effects: high PM_2.5 and O₃ generally correspond to lower NTL, though positive correlations persist in some areas due to industrial structures, highlighting the need for integrated policies that balance air quality management with sustainable urban planning; (6) the 2013 “Air Pollution Prevention and Control Action Plan” significantly strengthened the negative correlation between PM_2.5 and NTL in North China. However, O₃ concentrations increased by 28.9% after 2017, underscoring the challenge of coordinating VOC and NOx controls for long-term atmospheric sustainability. Full article

Salmonella enterica remains a major food safety concern in poultry, and processing-related stress can influence its survival and persistence. This study evaluated the phenotypic expression of S. enterica serotypes Kentucky (SK), Infantis (SI), Schwarzengrund (SS), and Typhimurium (ST) following antimicrobial and temperature stressors. A pre-harvest isolate of each serotype was gradually exposed to increasing concentrations of peracetic acid (PAA) and quaternary ammonium compounds (QACs), starting at 40 ppm and 1 ppm, respectively, until minimum inhibitory and bactericidal concentrations (MICs/MBCs) were established. Stressed cells were then subjected to cold (4 °C, 60 min) and heat (55 °C, 6 min) shock and assessed for sanitizer tolerance, biofilm formation and recovery, and antibiotic resistance. Sanitizer tolerance after daily conditioning varied among S. enterica serotypes, with ST and SK showing the highest tolerance to PAA and QACs, respectively. The tolerance of PAA variants increased by 10–20 ppm and QAC variants by 2–8 ppm following stress exposure. The double-stressed variants of ST significantly (p < 0.05) formed more biofilm than the control after PAA, whereas no significant differences were observed among the variants for other serotypes. Biofilm recovery was higher for the stressed variants of SI and SS (p < 0.05) following PAA stress but remained the same across all serotypes after QAC stress. QAC-stressed variants showed more phenotypic changes across the antibiotics tested. Notably, the stressed variants of SK, SS, and ST displayed increased MICs, including a 2- to 4-fold rise in azithromycin for the SK and ST variants. There was an increase in the MICs of ceftriaxone and nalidixic acid for some SK and SS variants. These findings suggest that environmental stress can significantly enhance the tolerance, survival, and persistence of S. enterica. Full article

Accessibility indicators derived from web-map platforms are increasingly used in sustainable spatial planning, service allocation, and land-value modelling, particularly in data-constrained regions. Yet the reliability of such source-dependent measures for decision-making remains insufficiently examined. Using paired parcel-level data from Khyber Pakhtunkhwa, Pakistan, this study conceptualizes accessibility as a spatial measurement process with structured source uncertainty by directly comparing platform-derived (PD) and field-verified (FV) nearest-facility distances across five facility types. Cross-source analysis reveals substantial facility-specific discrepancies in both magnitude and rank ordering, with certain facility types exhibiting near-random or reversed parcel rankings between sources. Spatial diagnostics further demonstrate that discordance events are geographically clustered rather than randomly distributed. An exploratory local amenity-density check further shows that mismatch prevalence varies systematically with nearby POI context, although the relationship is heterogeneous rather than uniformly sparse-driven. Under spatial block cross-validation, land-value models using FV accessibility consistently outperform PD-based models, while PD-based models display fold-level instability. Moreover, coefficient sign orientation and relative importance vary systematically across sources, indicating interpretation sensitivity to measurement choice. Importantly, reducing magnitude error alone does not restore decision reliability when ordering instability persists. These findings show that accessibility source choice can reshape spatial prioritization and inferred price gradients, introducing decision risk into sustainability-oriented planning. We therefore propose a minimum reliability protocol—including discrepancy profiling, ordering diagnostics, spatial discordance mapping, and spatially structured validation—to support transparent and defensible accessibility analytics in data-constrained environments. Full article

Oligometastatic prostate cancer represents a distinct biological state between localized and widely metastatic disease, characterized by a limited number of lesions. Stereotactic body radiotherapy (SBRT) has emerged as a key metastasis-directed therapy (MDT), enabling precise ablation of metastatic lesions with minimal toxicity. Prospective clinical trials such as SABR-COMET, STOMP, ORIOLE, RADIOSA, and EXTEND have shown that SBRT delays disease progression, prolongs progression-free survival, and postpones the need for systemic therapy, while maintaining a favorable safety profile. Nevertheless, methodological limitations persist, including heterogeneity in defining oligometastatic disease, variability in dosing and fractionation, and the lack of predictive biomarkers. Ongoing phase III trials aim to validate the integration of SBRT with modern systemic therapies, including next-generation androgen receptor pathway inhibitors, to optimize clinical outcomes in hormone-sensitive and castration-resistant oligometastatic prostate cancer. This review summarizes current evidence, clinical applications, and future directions for SBRT in this patient population. Full article

Climate change and progressive aridification represent a substantial threat to the sustainability of wild medicinal plant resources in Central Asia. Rheum tataricum L.f. (R. tataricum), a mesoxerophytic species with high pharmacological potential and a restricted distribution range, was selected as a model for investigating adaptive responses to combined climatic and edaphic stress. Relationships among climatic parameters, soil agrochemical characteristics, anatomical and morphological traits, and the metabolomic profile of roots and rhizomes were analysed across six ecopopulations distributed along latitudinal and altitudinal gradients in southern and western Kazakhstan. To quantify population-level vulnerability to climatic stress, a Climate Sensitivity Index (CSI) was calculated. All investigated ecopopulations exhibited high climate sensitivity (CSI = 0.30–0.40), indicating persistent climatic stress. Significant altitudinal dependence was detected for such anatomical traits, as primary cortex thickness, as well as for the accumulation of tannins, anthraquinones, and flavonoids. The metabolomic profile was strongly associated with seasonal precipitation, temperature, relative air humidity, soil agrochemical properties, and root elemental composition. These findings demonstrate pronounced anatomical and metabolomic plasticity in R. tataricum, which appears to function as a key adaptive mechanism in arid ecosystems. The results provide a scientific basis for sustainable bioprospecting, conservation of natural populations, and targeted cultivation aimed at obtaining specific metabolomic profiles. Full article

Atherosclerosis is a chronic inflammatory and metabolic disease driven by endothelial dysfunction, immune activation, vascular smooth muscle cell remodeling and aging-associated mitochondrial decline. Although lipid lowering remains the cornerstone of therapy, substantial residual inflammatory risk persists, highlighting the need for integrative regulatory targets. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, has emerged as a central metabolic sensor linking energy availability to transcriptional control of inflammation, oxidative stress, mitochondrial biogenesis and cellular senescence. Experimental studies across endothelial cells, macrophages and vascular smooth muscle cells consistently demonstrate that SIRT1 activation preserves nitric oxide bioavailability, suppresses ROS-dependent inflammasome signaling, modulates macrophage polarization, inhibits ferroptosis and maintains mitochondrial integrity. These cell-type-specific effects converge to reduce plaque progression and enhance fibrous cap stability in preclinical models. However, SIRT1 activity is hierarchically regulated by AMPK signaling and NAD⁺ availability and is influenced by aging, metabolic dysfunction and environmental stressors, underscoring its context-dependent function. Despite promising mechanistic data, clinical translation remains limited, suggesting that precision modulation strategies may be required. This review synthesizes current evidence and proposes that SIRT1 functions as a metabolic–inflammatory integrator within the atherosclerotic arterial wall, representing a potential but context-sensitive target for future cardiovascular therapies. Full article

Background: Laser peripheral iridotomy (LPI) is the first-line treatment for eyes with primary angle closure suspect (PACS), but the extent and durability of anterior chamber angle widening over time remain variable. Ultrasound biomicroscopy (UBM) allows detailed quantitative assessment of angle anatomy and underlying mechanisms of residual angle closure. Methods: In this prospective cohort study, 39 eyes of 20 PACS patients underwent UBM examination before LPI and at 1 month and 1 year post-procedure. Angle opening distance at 500 µm from the scleral spur (AOD500) and trabecular–ciliary process distance (TCPD) were measured in four quadrants under standardized light conditions. Paired comparisons and linear regression analyses were performed. Results: Mean AOD500 increased significantly from baseline (90.1 ± 52.5 µm) to 1 month (146.2 ± 58.2 µm, p < 0.001) and remained greater at 1 year (128.4 ± 48.8 µm, p < 0.001), with the largest changes observed in the superior quadrant. TCPD remained unchanged over time. Despite a patent iridotomy, iridotrabecular contact (ITC) persisted in 12.8% of eyes at 1 year. Plateau iris configuration was identified in 35.9% of eyes. Eyes with smaller baseline AOD500 showed a more limited anatomical response to LPI, although interaction testing did not reach statistical significance. Conclusions: LPI induces significant but partially attenuated anterior chamber angle widening at one year in PACS eyes. A substantial subset exhibits persistent angle closure, frequently associated with plateau iris configuration, underscoring the need for continued post-LPI anatomical surveillance and mechanism-based management. Full article

Chieng Hac in northern Vietnam is expanding maize cultivation, intensifying water competition and soil erosion. This study mapped regional water balance and erosion using remote sensing and GISs by coupling the Thornthwaite–Mather (TM) water balance model with the Revised Universal Soil Loss Equation (RUSLE) at 12.5 m resolution. Land cover was classified into maize, tree crops, paddy, forest, and other types using Random Forest. The TM model used 2021 precipitation and temperature measurements to estimate evapotranspiration, surplus, and deficit, while the RUSLE quantified soil loss. Two scenarios were evaluated: a baseline reflecting existing land use and an adjusted case applying strip cropping on 10–20° maize slopes and converting maize to tree crops on slopes > 20°. Tree crop conversion increased evapotranspiration and prolonged seasonal deficits relative to maize, increasing water deficit from 1013.6 to 1022.2 mm/year. In contrast, the interventions reduced mean soil loss from 15.52 to 11.51 t/ha/year, with the largest decline in the 5–25 t/ha/year class. Residual hotspots persisted on steep slopes and near drainage lines. The integrated framework highlights trade-offs between erosion control and seasonal water availability, supporting slope-based land-use planning in upland agricultural systems. These findings offer guidance for slope-based land-use planning by indicating that intervention priorities should vary depending on slope conditions and local water availability. Full article

Background: Sub-Saharan Africa is undergoing a rapid epidemiological transition marked by a growing burden of non-communicable diseases, including breast, cervical, ovarian, and uterine cancers, which constitute major causes of morbidity and mortality among women in the region; however, comprehensive assessments of long-term trends and regional heterogeneity remain limited. This study examines the burden and temporal trends of breast, cervical, ovarian, and uterine cancers across sub-Saharan Africa from 1990 to 2023. Methods: A retrospective ecological analysis was conducted using data from the latest Global Burden of Disease 2023 study. Age-standardised incidence rates, mortality rates, and disability-adjusted life year rates were estimated for breast, cervical, ovarian, and uterine cancers across 48 sub-Saharan African countries and four sub-regions. Temporal trends were assessed from 1990 to 2023, with percentage changes calculated to characterise epidemiological transitions. Geographic variation and age-specific patterns were examined to identify high-burden settings and priority populations. Results: Between 1990 and 2023, the burden of all four cancers increased substantially across sub-Saharan Africa, with significant regional and country-level heterogeneity. Breast cancer exhibited the largest absolute burden, with incidence increasing by over 120 percent and mortality by more than 80 percent, particularly in Central and Western Africa. Cervical cancer remained the leading cause of cancer-related mortality among women in Eastern and Southern Africa, despite evidence of stabilisation or decline in selected countries. Ovarian and uterine cancers demonstrated sustained upward trends, especially in Central Africa, with high mortality-to-incidence ratios indicating late diagnosis and limited treatment access. Across all cancer types, Central and Eastern sub-Saharan Africa consistently experienced the highest disability-adjusted life year burdens. Conclusions: The burden of the selected cancers in sub-Saharan Africa has increased markedly over the past three decades, with persistent regional inequities reflecting gaps in prevention, early detection, and treatment capacity. Strengthening cancer surveillance systems, expanding equitable access to screening and vaccination programmes, and improving diagnostic and treatment infrastructure are critical to reversing current trends. These findings provide region-specific evidence to guide cancer control priorities and resource allocation across sub-Saharan Africa. Full article

The Black Sea is highly vulnerable to environmental degradation, making the evaluation of contaminant transfer within its food webs essential for ecosystem protection, sustainable resource management, and human health risk assessment. Marine organisms accumulate contaminants through three main processes: bioconcentration (direct uptake from the abiotic environment), biomagnification (trophic transfer through consumption of contaminated prey), and bioaccumulation, which integrates contaminants from all exposure pathways. Despite numerous studies reporting contaminant concentrations in Black Sea waters, sediments, and biota, integrated analyses of trophic transfer within both pelagic and benthic food webs in the Romanian coastal sector remain limited. This study assessed the bioamplification of heavy metals—HMs, persistent organic pollutants—POPs (OCPs, PCBs) and polycyclic aromatic hydrocarbons—PAHs along the main pelagic and benthic food webs in the Romanian coastal sector, based on concentrations measured in representative invertebrate and fish species. The results revealed a compartment-driven contamination pattern, with the benthic food web functioning as an important reservoir and transfer pathway. Heavy metals showed variable and context-dependent trophic transfer, with selective amplification for Cu and Ni in some benthic links, trophic dilution or neutral transfer for Cd and Pb, and more consistent retention for Cr. In contrast, several PCB congeners showed clear biomagnification, particularly in benthic predator–prey relationships. PAHs displayed compound-dependent trophic transfer, with more pronounced amplification in benthic pathways. Overall, biomagnification was stronger for organic pollutants, particularly PCBs, than for heavy metals. The study contributes to two United Nations Sustainable Development Goals (SDGs): SDG 14 (Life Below Water) and SDG 12 (Responsible Consumption and Production). Full article

Mountain Social–Ecological Systems (MtSES) are global assets, providing essential ecosystem services to nearly half of humanity, yet they are disproportionately vulnerable to global change, experiencing “polytraps” of depopulation, poverty, and environmental degradation. Despite the inherent human dimension in sustainability, the social pillar remains conceptually chaotic, forming a highly fragmented “publication labyrinth”, and is often neglected in favor of more easily quantifiable environmental and economic metrics. These oversights leave mountain communities in a precarious state, underscoring an urgent need for robust, context-specific assessment tools. This paper addresses this critical gap by employing a two-step methodology: first, a literature review identifies prevailing social sustainability issues in mountain contexts; second, a comparative analysis evaluates prominent frameworks and indicator-based tools against these themes, using Ostrom’s multi-tier Social–Ecological Systems (SES) framework as the theoretical lens. Our findings reveal a persistent environmental bias in MtSES research and highlight the necessity for frameworks that integrate local knowledge, address power imbalances, and support bottom-up governance. A tool is proposed with indicators specifically for mountainous contexts. This study contributes to theory by offering a structured approach to unpack the elusive “social” in SES and to practice by providing a model and tool for developing actionable, context-sensitive social sustainability assessments, thereby fostering resilience and equitable development in vulnerable mountain regions. Ultimately, by operationalizing these social dimensions, this research provides a direct roadmap for achieving key United Nations Sustainable Development Goals in marginalized high-altitude contexts, particularly focusing on No Poverty (SDG 1), Good Health and Well-being (SDG 3), Reduced Inequalities (SDG 10), Sustainable Communities (SDG 11), and Peace, Justice, and Strong Institutions (SDG 16). Full article

Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer closely associated with smoking and alcohol consumption, with a higher incidence in men. Despite changes in treatment strategies, poor survival persists in most patients, highlighting the need for novel and improved therapeutic options. Naphthoquinone analogs are being investigated because of their active redox structure and broad pharmacological profile; they demonstrate cytotoxic antitumor activity, making them potential candidates for new drug agents. Objective: This study investigated new benzyl-naphthoquinone compounds as potential anticancer agents for various genotypes of oral squamous cell carcinoma (OSCC) and other cancer cells. Methods: This study reports the synthesis and evaluation of a series of eight benzyl-naphthoquinone compounds against oral squamous cell carcinoma. Results: Four compounds 1–4 showed the best cytotoxic profiles, with a selectivity index ≥ 3 for all OSCC cell lines tested. Compound 1 was the most selective compound in all OSCC models, showing a higher selectivity index than both carboplatin and shikonin. Furthermore, compound 1 induced DNA fragmentation, cell-cycle arrest, and caspase-3/7 activation, changes consistent with apoptosis, and time-lapse imaging corroborated the apoptotic phenotype. Hemolysis assays showed minimal toxicity in human erythrocytes, and acute in vivo evaluation in mice revealed no evident adverse effects under the conditions tested, indicating low acute toxicity, although more detailed histopathological and biochemical studies will be required to fully establish the safety profile. Molecular modeling suggested that compound 1 may interact with topoisomerase II, RSK2, and PKM2, which could contribute to the activation of apoptotic pathways, although these interactions remain predictive and require biochemical validation. Finally, in silico analysis of physicochemical and ADMET parameters indicated properties compatible with oral absorption and systemic exposure, together with predicted low toxicity; however, these results are model-based and should be confirmed experimentally. Conclusions: Based on these findings, compound 1 emerges as a promising lead candidate for the development of a novel chemotherapeutic agent against OSCC, with potential therapeutic efficacy against other cancer types. Full article

Quantitative sensory testing (QST), including temporal summation of pain (TSP) and pressure pain threshold (PPT) assessments, was conducted to evaluate the diagnostic validity and immediate therapeutic efficacy of the manual therapy technique Fascial Counterstrain (FCS). A single patient with persistent lower back and referred leg pain was evaluated and treated by a certified FCS practitioner. A clinical diagnosis of left S1–S2 radiculitis (FCS criteria) was established and corroborated by elevated pre-treatment TSP and reduced PPT measures in the affected dermatomes, indicating nerve root irritation and central sensitization. Immediate post-treatment TSP and PPT assessments demonstrated near-complete normalization of wind-up in the involved S1 and S2 dermatomes, along with a substantial improvement in three-trial-average PPT measurements of the S1–S2 musculature from 2.4 kg/cm² to 6.1 kg/cm². This case report provides preliminary evidence supporting the diagnostic process and immediate post-treatment efficacy of FCS in patients with lower back pain and central sensitization. Full article

Ecosystem transpiration (T) is the core process in terrestrial water and carbon cycles. Accurately estimating T is critical to improving evapotranspiration (ET) models and understanding global ecosystem responses to climate change. In this study, we evaluated four ET partitioning methods (TEA, Z16, L19, and Y21) using 368 global eddy covariance (EC) sites and 15 sap flow sites. Intercomparison results showed that TEA, Z16, and Y21 maintained good consistency, whereas L19 exhibited lower agreement, primarily due to its high sensitivity to energy closure errors and poor non-linear fitting accuracy under extreme conditions. Validation against sap flow data indicated that Z16 performed best (R² = 0.45, KGE = 0.52), followed by Y21, while TEA had the lowest accuracy due to systematic overestimation driven by unremoved persistent background soil evaporation in its training dataset. Global analysis revealed that mean annual T ranged from 213 mm yr⁻¹ (Z16) to 294 mm yr⁻¹ (TEA), with annual T/ET varying between 0.45 (Z16) and 0.63 (TEA). Trend analysis further showed consistent increasing trends across all four methods for both annual T (0.33–0.83 mm·yr⁻²) and annual T/ET (0.0015–0.0019 yr⁻¹). Additionally, a notably stronger relationship was found between gross primary productivity (GPP) and T than between GPP and ET. Despite substantial differences in model structures, these methods effectively capture the temporal dynamics of T and the coupled relationships between ecosystem carbon and water fluxes. Our findings provide critical benchmarks for terrestrial water cycle modeling and sustainable water resource management under a changing climate. Full article