Search Results (1,797)

Gene therapy relies on safe and efficient delivery systems, yet traditional viral vectors and synthetic polymers often fail to meet these requirements due to immunogenicity and biocompatibility concerns. This review highlights self-assembling short peptides as a highly programmable and biocompatible non-viral platform uniquely positioned to overcome these translational bottlenecks. To provide a comprehensive overview of next-generation gene delivery, we systematically trace the trajectory from fundamental chemistry to clinical applications. First, we elucidate the supramolecular interactions and mechanisms driving peptide–nucleic acid co-assembly. Second, we outline concrete design strategies, detailing how sequence engineering and environmental responsiveness dictate the formation of optimized nanomorphologies. Third, we critically analyze how these nanocarriers navigate critical physiological and intracellular barriers, with a specific focus on cellular uptake, endosomal escape, and cargo release. Finally, we demonstrate the platform’s versatility in emerging frontiers, particularly mRNA vaccines and CRISPR/Cas9 gene editing. We conclude by identifying current obstacles to clinical translation and proposing future directions centered on multifunctional integration and stimuli-responsive design. Full article

Objectives: This overview of systematic reviews aimed to synthesize and critically evaluate the current evidence on the effects of exercise performed under hypoxic or altitude conditions in adults, with particular attention to studies reporting altitude-related clinical outcomes. Materials and Methods: Following PRIOR and PRISMA guidelines, and with the protocol registered in PROSPERO CRD420261325746, a comprehensive search was conducted on 22 February 2026 across Medline/PubMed, Scopus, Web of Science, Epistemonikos, and Preprints.org, using the query “Exercise AND Hypoxic AND Altitude Sickness.” Because the search included “Altitude Sickness,” this review may miss some studies on performance or physiological adaptations under hypoxia. Eligibility was defined according to the PICOS framework, including only systematic reviews with or without meta-analyses in adults exposed to normobaric or hypobaric hypoxia. Methodological quality was assessed using AMSTAR 2. Results: A total of 137 records were identified (114 from databases and 23 through citation tracking), of which 28 systematic reviews met inclusion criteria. Nineteen included quantitative meta-analyses. Structured altitude training strategies—live high–train low (LHTL), live low–train high (LLTH), and live high–train high (LHTH)—were generally associated with improvements in maximal oxygen uptake and hematological parameters, particularly in trained and athletic populations. In contrast, acute hypoxic exposure was consistently associated with reduced exercise performance and increased susceptibility to altitude-related symptoms in unacclimatized individuals. Evidence regarding effects on body composition and metabolic outcomes was heterogeneous and inconsistent. According to AMSTAR 2, most meta-analyses presented critically low or low methodological quality. Conclusions: Exercise under hypoxic conditions may enhances aerobic and hematological adaptations in trained populations, whereas acute exposure tends to impair performance and entails clinical risks. However, given the restricted search strategy, substantial heterogeneity, lack of formal overlap quantification, and the predominance of low methodological quality reviews, these findings should be interpreted with caution. Evidence on metabolic benefits remains limited, highlighting the need for further high-quality systematic reviews and meta-analyses to clarify optimal hypoxic training protocols and outcomes. Full article

Understanding the factors controlling nitrogen use efficiency (NUE) in paddy soil is essential for optimizing the application of relatively costly nitrogen (N) fertilizer for rice cultivation. Therefore, an experiment was conducted to assess the seasonal variation in NUE among three Aus, five Aman, and three Boro rice varieties at the Bangladesh Agricultural University (BAU) farm during the Aus, Aman, and Boro cropping seasons. In addition, the variation in the NUE of rice was assessed among eight soil series throughout Bangladesh during the Boro season. The experiment included N control and N application at the recommended rates. The results showed that BRRI dhan48 outperformed the other varieties in the Aus season, with the maximum agronomic efficiency (AE). In contrast, BRRI dhan65 was better in terms of physiological efficiency (PE), whereas BRRI dhan42 showed the lowest AE. Throughout the Aman period, BR11 exhibited the best AE and PE. During the Boro season, BRRI dhan29 and BINA dhan-6 demonstrated the maximum AE, PE, and apparent recovery efficiency (ARE). Grain yield, nitrogen response, AE, and ARE were markedly higher in the Boro season than in the Aus and Aman seasons. Among the eight locations, the highest grain yield of BINA dhan-7 in the Aman season was recorded in the Noadda soil series, followed by Barisal and Sara, with an AE extended from 11 to 19 kg grain kg/N applied, PE from 31 to 61 kg grain kg/N uptake, and ARE from 21% to 41%. These findings highlight the significant variability in NUE among rice varieties, seasons and soil series, suggesting the importance of variety, location and season-specific N management. Full article

Cadmium (Cd) is a potentially toxic element that impairs plant growth and threatens food safety and human health. This study aimed to investigate the effects of sulfur (S) supplementation on Cd uptake and tolerance in rice under hydroponic conditions. Rice seedlings were exposed to Cd stress and treated with S at different concentrations. Physiological traits, oxidative damage markers, thiol compounds, and ionomic profiles in rice plants were assessed. S supplementation reduced Cd-induced growth inhibition, restoring plant biomass. Although Cd accumulation increased with S treatment, it was accompanied by enhanced antioxidant responses, scavenging reactive oxygen species (ROS) and malondialdehyde. S application increased the production of thiol-containing compounds, including γ-glutamylcysteine, glutathione, and phytochelatins, which helped chelate Cd and sequester it in vacuoles, particularly in roots. Additionally, S supplementation altered the essential nutrient composition in rice tissues, particularly the uptake of N, P, and K, while influencing levels of Ca, Mg, and other essential elements. S supplementation enhanced rice tolerance to Cd stress by reestablishing ROS balance, activating thiol-based detoxification pathways, and regulating mineral nutrient balance. Furthermore, sulfur (S) exhibited a dual effect in plants, enhancing cadmium (Cd) uptake while also promoting its detoxification, underscoring its role in improving crop resilience in contaminated soils. Full article

Surface-enhanced Raman spectroscopy (SERS) amplifies Raman scattering by placing molecules in the near-field of plasmonic nanostructures, enabling label-free molecular fingerprinting. While attractive for living cell phenotyping, many cellular SERS works rely on internalized colloidal nanoparticles, leading to variable uptake/localization, aggregation-driven hotspot fluctuations, and potential cellular perturbation. Here, we report a chip-like Au/SiO₂ nanolaminate SERS substrate that supports direct culture and label-free measurements of living cells on spatially defined hotspots without nanoparticle uptake. The periodic nanolaminate forms dense nanogaps and is engineered for 785 nm excitation, providing uniform enhancement over a large, culture-compatible area with high hotspot uniformity. By engineering the cell–substrate nano–bio interface, the platform enables reproducible acquisition of intrinsic cellular vibrational fingerprints under physiological conditions without Raman tags. Using MCF-7 and MDA-MB-231 breast cancer cells, we collected hundreds of spectra per line, and MDA-MB-231 exhibited broader spectral variations, indicating greater heterogeneity. Principal component analysis and linear discriminant analysis achieved 99% classification accuracy for MCF-7 and MDA-MB-231, and bright-field imaging confirmed preserved adhesion and canonical morphologies. This chip-based, label-free living cell SERS platform enables scalable, nonperturbative phenotyping and may support rapid malignancy classification and treatment response screening across subtle cancer states. Full article

The liver’s anatomic position and immune specialization make it both a major target and a major filter for systemically delivered therapeutics. Because portal venous inflow exposes the liver early to gut-derived molecules and exogenous compounds, many intravenously administered agents, including gene-based medicines and their viral and non-viral delivery systems, preferentially enter and accumulate in hepatic tissue. This review synthesizes how core liver physiology and immunobiology influence the performance, safety, and clinical translation of genomic medicines in hepatology, and outlines near-term practice and research shifts likely to define a genomics-driven future in liver disease care. We review the hepatic microarchitecture relevant to therapeutic trafficking, including sinusoidal transit, the space of Disse, hepatocyte uptake, and hepatobiliary elimination, and highlight the gatekeeping roles of liver sinusoidal endothelial cells and Kupffer cells in clearing particulate material and shaping inflammatory signaling. We then discuss how these same features create both opportunities, such as efficient hepatic targeting, and constraints, including innate immune activation, vector clearance, and variable intrahepatic distribution, for DNA- and RNA-based platforms. Finally, we propose five actionable developments poised to move genomics from a niche tool to a routine component of hepatology practice: earlier genomic testing in unexplained liver disease, multidisciplinary hepatology genome rounds, a centralized liver-specific gene resource, genetics-aware clinical trial design, and expansion of genetic therapies. Integrating liver biology with genomic medicine is essential to improve diagnostic yield, personalize therapy, and accelerate translation of gene-based treatments while mitigating immunologic and delivery-related barriers. Full article

Heatwaves, intensified by climate change and urbanization, pose increasing threats to human health, with occupational populations facing disproportionate risks due to prolonged exposure and high metabolic demands. Existing evidence remains fragmented, particularly regarding the integration of acute and chronic health effects in workplace settings. This narrative review synthesizes current knowledge on occupational heat exposure, highlighting emerging risks such as cumulative physiological strain, heat-related chronic diseases, and mental health impacts. We identify key occupational-specific pathways that amplify vulnerability beyond that of the general population. Despite growing awareness, substantial gaps persist in the implementation of effective adaptation strategies, especially in low- and middle-income countries, where regulatory, economic, and structural barriers limit intervention uptake. To address these challenges, we emphasize the need for adaptive work–rest scheduling, dynamic early warning systems, and cross-sectoral collaboration to enhance occupational heat resilience under a changing climate. Full article

Understanding the soil–plant transfer of both essential and non-essential elements is crucial for evaluating the crop nutritional quality, environmental interactions, and food safety. This study delivered a multiyear and multielement assessment under field conditions of the element uptake, translocation, and accumulation in raspberry (Rubus idaeus L.), based on data collected over two growing seasons (2024–2025) in two contrasting Romanian agroecosystems. Two commercial cultivars (Opal and Delniwa) were investigated under fertilized and unfertilized conditions. The concentrations of essential macroelements such as Ca, Mg, Na, and K, as well as trace elements (Li and Sr), were determined in soils and fruits using ICP-OES and AAS. The soil–fruit transfer was quantified through the transfer factor, assisted by a robust statistical framework which integrated spatial–temporal variability and non-parametric analysis. The results highlighted two contrasting accumulation regimes. The essential macroelements revealed a dynamic uptake pattern driven by the physiological demand, soil availability, and fertilization. K exhibited the highest transfer capacity, while Ca had a restricted translocation to the fruits, due to the intrinsic transport limitations. On the other hand, Li and Sr revealed a constrained accumulation, characterized by low concentrations, weak responsiveness to fertilization, and a strong dependence on the soil geochemical background and interannual dilution processes. The spatial variability between the cultivation sites and year-to-year changes in the dilution intensity was evidenced as the dominant driver of the transfer efficiency, while the varietal differences had a secondary but detectable role, mainly for the Ca–Sr discrimination. Overall, the results evidenced that the multielement accumulation in the raspberries was governed by the interplay between the soil geochemistry, physiological transport constraints, and environmental variability. Furthermore, the research provided a field-based, multiyear evidence supporting improved soil management, cultivar selection, as well as the strategies that may increase the fruit nutritional quality while minimizing the trace element risks. Full article

Antioxidants, such as phenolic compounds, are essential for mammal physiology. Significant research made on the gut–brain axis has produced volumes of evidence indicating that some plant-derived phenolic compounds can reach brain cells to exert protective effects on them, mainly by maintaining and/or restoring redox homeostasis. Their systemic uptake and transport might be determined by the phenolic’s physicochemical properties, along with complex interactions with protein transporters and carriers, including GLUT, SGLT1, ABC transporters (P-glycoprotein, breast cancer resistance protein), albumin, fibrinogen, organic anion and cation transporters, and MATE1. The present work focuses on the chemical interactions and transport pathways of some phenolic compounds to reach brain cells. Full article

Sweet potato (Ipomoea batatas (L.) Lam) is an important food and energy crop. Soil salinization is a major abiotic stress that limits agricultural productivity and severely reduces yield of crops. Protein hydrolysates, as a class of natural biostimulants, have gained increasing attention for their potential to improve crop yield, quality and stress tolerance. This study investigated the effects of peptides from swine blood (PSB) on high salinity stress tolerance in sweet potato. Application of PSB promoted the growth of both aerial and underground parts of sweet potato under normal and high-salinity conditions. Further analysis revealed that, under high salinity stress, exogenous PSB up-regulated the expression of genes associated with stress responses, increased the accumulation of organic osmotic adjustment compounds such as free amino acids, promoted K⁺ uptake to elevate the K⁺/Na⁺ ratio, and enhanced the activity of key antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) involved in the reactive oxygen species-scavenging system. These biochemical responses contributed to maintaining cellular osmotic balance and redox homeostasis, protecting the cell membrane from damage while preserving its structural integrity and normal physiological functions, and improving photosynthetic efficiency, thereby enhancing high salinity stress tolerance in sweet potato. Thus, PSB holds significant potential as an effective natural biostimulant for sweet potato cultivation in saline soils. Full article

This study develops and validates an integrated framework that combines UAV multispectral imagery and canopy structural metrics with gridded climatic variables to predict soybean (Glycine max (L.) Merrill) foliar potassium (K) status and grain yield. Field experiments were conducted over three consecutive growing seasons (2022–2023, 2023–2024, and 2024–2025) under different potassium fertilisation strategies and environmental conditions. Machine learning models, particularly the random forest algorithm, were applied to multisource datasets, including UAV-derived canopy structural traits (height and canopy area), spectral indices (NDVI), meteorological variables, and fertilisation information. The foliar K prediction models achieved high accuracy (R² up to 0.85), while the yield prediction models achieved R² values between 0.71 and 0.81. The inclusion of the potassium rate and fertilisation strategy further improved model performance, highlighting the strong influence of potassium supply and fertilisation management on plant physiological responses. Interestingly, compared with those required to stabilise grain yield, foliar potassium saturation occurred at substantially higher K₂O rates, indicating the occurrence of luxury potassium uptake. The association of UAV-derived canopy metrics with this pattern suggests that remote sensing may help detect subtle nutritional dynamics that are not directly reflected in yield responses. Model interpretability using SHAP analysis identified relationships within the analysed dataset that were consistent with physiological expectations, with positive contributions associated with canopy vigour and negative contributions associated with thermal stress. In addition, probabilistic SHAP analysis provided a decision-oriented perspective by quantifying yield probabilities under contrasting potassium management regimes and climate scenarios. Overall, within the experimental conditions studied, the proposed framework enabled a rapid assessment of crop nutritional status, yield prediction, and the evaluation of fertilisation strategies. The integration of UAV data, climatic variables, and machine learning provides an interpretable basis for potassium management and soybean yield forecasting within the experimental conditions studied, while broader transferability requires external validation. Full article

Homeobox protein MEIS2 has been strongly implicated in colorectal cancer (CRC) progression and metastatic potential, making its targeted inhibition a promising therapeutic strategy. However, recently developed MEIS inhibitors are limited by poor aqueous solubility, instability under physiological conditions, and insufficient intracellular accumulation, which restrict their clinical applicability. To overcome these challenges, a multifunctional hybrid nanoemulsome system was developed by integrating boron–silane-doped carbon dots (CDs) with chitosan via glutaraldehyde crosslinking, followed by emulsification with oleic acid and non-ionic surfactants (Span 80 and Tween 20/80) in the presence of a MEIS inhibitor (MEISi-2). The resulting composite exhibited high structural stability, excellent biocompatibility, and a drug encapsulation efficiency of 96.2%. Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) analyses confirmed successful hybridization and the formation of nanoemulsions with an average particle size of approximately 320 nm following drug loading. The system demonstrated controlled drug release under physiological conditions. In vitro studies using HCT116 CRC and HaCaT healthy keratinocytes revealed effective cellular uptake and selective cytotoxicity. The intrinsic fluorescence properties of CDs enabled real-time monitoring of intracellular drug delivery via DAPI-channel imaging. Overall, this hybrid nanoemulsome platform provides a stable and efficient delivery system for MEIS inhibitors and represents a promising strategy for the treatment of CRC. Furthermore, this approach may be extended to other poorly soluble amphiphilic therapeutic agents. Full article

Background/Objectives: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (¹¹¹In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. Methods: N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. Results: In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca²⁺ and Mg²⁺ had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, ¹¹¹In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). Conclusions: A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required. Full article

Against the backdrop of accelerated terrestrial hydrological cycling and the increasing concurrence of drought-heatwave compound extremes under global warming, regional land-atmosphere coupling has emerged as a central mechanism shaping climate feedbacks and trajectories of ecosystem carbon uptake. However, prior studies spanning climatic regimes, observational scales, and data sources have often yielded contradictory conclusions. Here, we challenge these fragmented perspectives by constructing an integrated LST-SM-ET-GPP chain that jointly represents land surface temperature, soil moisture, evapotranspiration, and gross primary productivity, thereby linking water availability, surface energy balance, and plant physiological processes within a unified framework. We synthesize a conceptual diagnostic roadmap for interpreting land-atmosphere coupling across observations and models. When ecosystems operate in humid, energy-limited environments, radiative and advective controls should be prioritized to diagnose system forcing. By contrast, as the system becomes water-depleted, attribution must shift to a nonlinear regime transition framework governed by a critical soil moisture threshold. This threshold mechanism implies that, once the system enters the moisture-limited regime, even modest declines in soil moisture can trigger a rapid weakening of evaporative cooling, substantially amplifying LST anomalies and strongly suppressing GPP. The competitive regulation of stomatal conductance by atmospheric demand (vapor pressure deficit, VPD) and terrestrial supply (rootzone soil moisture) further explains why the “dominant” controlling factor can dynamically reverse across hydrothermal states, timescales, and stages of extreme-event evolution. Notably, the steady-state coupling assumption may break down under flux “flooring” during extreme drought, or when structural buffering such as deep root water uptake is present, delineating strict applicability bounds for existing diagnostic frameworks. Finally, current assessments remain constrained by multiple uncertainties, particularly the lack of ET partitioning constraints, representativeness biases arising from clear-sky observations and sampling-depth limitations, and systematic errors in Earth system model simulations during the warm season. Full article

Excess post-exercise oxygen consumption (EPOC) reflects cardiorespiratory fitness, energy metabolism and the residual physiological effects of preceding exercise. We aimed to compare EPOC profiles of master swimmers across different age groups and performance levels. Fourteen male master swimmers performed a 200 m all-out front crawl and breath-by-breath gas exchange and their heart rates were recorded during exercise and for 5 min post-exercise. A single exponential regression model was fitted to the post-exercise oxygen uptake kinetics to determine the EPOC amplitude, time constant and time delay. The EPOC magnitude was calculated as the area under the oxygen uptake–time curve. Swimmers were grouped into younger vs. older and faster vs. slower clusters using the 50th percentile, and the associations between age, performance and physiological variables were examined. Older swimmers were slower and showed a lower peak oxygen uptake than their younger counterparts (213.9 ± 27.9 vs. 165.7 ± 24.9 s and 39.1 ± 4.8 vs. 50.2 ± 8.1 mL∙kg⁻¹∙min⁻¹; p < 0.05). Slower swimmers were older and displayed a lower EPOC amplitude than faster performers (69.8 ± 7.3 vs. 45.7 ± 1.7 years and 23.2 ± 4.0 vs. 36.8 ± 10.2 mL∙kg⁻¹∙min⁻¹; p < 0.05). Although many of the variables did not differ between groups, effect sizes were moderate to very large (except for time constant and time delay). The swimmers’ age related directly to their performance and inversely to their peak oxygen uptake, peak heart rate and EPOC amplitude, while performance presented inverse associations with peak oxygen uptake, peak heart rate, EPOC amplitude and EPOC magnitude (p < 0.05). Master swimmers of different ages and performance levels exhibited distinct EPOC characteristics, which may provide relevant information regarding the individualisation of training and recovery strategies in this population. Full article