Search Results (31,890)

Air density and pressure above the Earth’s surface in the tropospheric region depend on altitude relative to sea level. When a given amount of pollutant gas enters the atmosphere at sea level, it produces a contaminated air mixture; if the same amount of pollutant gas enters the atmosphere at a location situated at higher altitude, atmospheric pollution certainly also occurs. However, the relative compositions are not the same in both cases due to the greater air density present at sea level compared to the air density at higher altitude. Current regulatory frameworks, including the National Ambient Air Quality Standards (NAAQS) of the United States Environmental Protection Agency and the Air Quality Guidelines (AQG) of the World Health Organization, establish constant numerical values for air quality standards uniformly applicable at all geographic locations, regardless of altitude, resulting in inadequate health protection for millions of people. To address this critical gap, a universal adjustment factor for atmospheric pollutant gas concentrations at different altitudes has been derived from first principles of atmospheric physics; this factor is $f=e^{-0.000115 h}$, where h is expressed in meters, assuming air at constant temperature given that small temperature variations do not substantially influence atmospheric density and pressure or pollutant concentrations at different altitudes. The factor was systematically applied to the NAAQS and WHO AQG, demonstrating that for altitudes of 3500 m, representative of cities such as Cusco, Peru, the adjusted standards are approximately 67% of the nominal values established at sea level, preserving the gaseous pollutant–air proportionality. Experimental measurements of atmospheric density in six Peruvian cities distributed along an altitudinal gradient of 0–3826 m validated the theoretical model with relative deviations less than 5%, confirming the physical consistency of the derived factor. The importance of this research lies in adequately regulating air quality standards related to public health and the environment, supporting the implementation of equitable environmental policies aligned with the United Nations (UN) 2030 Sustainable Development Goals, and establishing that the constant values defined at sea level must be adjusted according to the aforementioned factor when geographic altitude is considered. Full article

Nitrogen-modified atmosphere technology, due to its effectiveness in pest control, is widely used in grain storage as an eco-friendly preservation method. This study compared the quality changes in unhulled rough rice (paddy) stored under nitrogen-modified atmosphere and conventional conditions. Fatty acid value (FAV), reactive oxygen species (ROS) content, coenzyme levels, antioxidant enzyme activities, and concentrations of central carbon metabolism-related metabolites of paddy were monitored during storage under different storage conditions. The results revealed that compared to conventional storage, nitrogen-modified atmosphere resulted in lower FAV and ROS levels, as well as higher pyridine nucleotides contents and antioxidant enzyme activities, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione reductase (GR). Metabolomic profiling demonstrated that N₂-MAS induced metabolic changes characterized by the down-regulation of 2-hydroxyglutaric acid and the up-regulation of fructose 6-phosphate, glucose 1-phosphate, glycerol 3-phosphate, gluconic acid, fumaric acid, and malic acid, which collectively contribute to reduced oxidative damage and enhanced preservation quality. These findings elucidated the mechanism of N₂-MAS-delayed quality deterioration and revealed the regulatory role of the antioxidant system and central carbon metabolism. Full article

Caspases are known for their roles in cell death and inflammation. However, emerging evidence suggests they also mediate non-lethal processes, governed by a finely tuned balance of localization, activity, kinetics, and substrate availability. Given that many caspase substrates are implicated in mechanoadaptive processes, we investigated if caspases contribute to morphological adaptation of human pulmonary artery endothelial cells to fluid shear stress and other morphology-altering stimuli in vitro. Using selective inhibitors, we screened all major caspases for a role in endothelial cell adaptation to unidirectional laminar shear stress (15 dyn/cm², 72 h). Selective inhibition of caspase-6, but not other caspases, impaired morphological shear adaptation. Only 5.5% of caspase-6-inhibited cells shear-adapted vs. 75.2% of vector controls. Live-cell FRET imaging revealed progressive caspase-6 activation starting at 18 h of shear stress, coinciding with the onset of morphological remodeling. The active caspase-6 localized predominantly perinuclearly, while caspase-3 remained inactive throughout shear exposure. Caspase-6 inhibition did not affect elongation in response to alternative biomechanical or biochemical stimuli, including uniaxial cyclic stretch (5%, 1 Hz), spatial confinement on narrow micropatterned RGD-lines, or TNF-α stimulation, nor did it impair cell adhesion, directed migration, wound healing, or barrier recovery after wounding. Our study uncovers a previously unidentified role of caspase-6 as a non-apoptotic, mechanosensitive effector specifically required for shear-induced morphological adaptation of pulmonary artery endothelial cells, highlighting a novel regulatory axis in vascular mechanoadaptation. Full article

Ischemia/reperfusion (I/R) injury is a major complication in lung transplantation. Recent evidence suggests that mitogen-activated protein kinases (MAPKs) such as p-38 mitogen-activated protein kinase (p-38 MAPK) and extracellular signal-regulated kinase (ERK), along with functionally related kinases like phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), contribute to I/R pathophysiology by mediating inflammatory and stress-response signaling. MicroRNAs (miRNAs) also play a regulatory role in these processes. Lidocaine has demonstrated anti-inflammatory activity in several tissues; however, its ability to modulate miRNA expression and kinase activation in the lung is not yet fully understood. This study investigated the involvement of these signaling molecules in lung I/R injury and evaluated the modulatory effect of intravenous lidocaine in a porcine lung auto-transplantation model. Eighteen large white pigs were assigned to sham-operated (n = 6), control (lung auto-transplantation, n = 6), or lidocaine-treated (n = 6) groups. Lidocaine was administered as a 1.5 mg/kg bolus followed by a continuous infusion (1.5 mg·kg⁻¹·h⁻¹). Lung biopsies were collected before ischemia, before reperfusion, and at 30- and 60-min post-reperfusion to assess total and phosphorylated levels of p-38 MAPK, ERK, PI3K, and AKT (Thr308, Ser473), along with miR-126, miR-142-5p, miR-152, and miR-155 expression. I/R increased p-38 MAPK and AKT, and enhanced phosphorylation of all four kinases. miRNA levels were also upregulated. Lidocaine partially or completely attenuated these changes. These findings support a role for these molecular pathways in lung I/R injury and suggest that lidocaine may offer protective effects through their modulation. Full article

Optical fiber technology is becoming essential in modern radiation therapy, enabling precise, real-time, and minimally invasive monitoring. As oncology moves toward patient-specific treatment, there is growing demand for adaptable and biologically compatible sensing tools. Fiber-optic systems meet this need by integrating into clinical workflows with highly localized dosimetric and spectroscopic feedback. Their small size and flexibility allow deployment within catheters, endoscopes, or treatment applicators, making them suitable for both external beam and internal therapies. This paper reviews the fundamental principles and diverse applications of optical fiber sensing technologies in radiation oncology, focusing on dosimetry, spectroscopy, imaging, and adaptive radiotherapy. Implementations such as scintillating and Bragg grating-based dosimeters demonstrate feasibility for in vivo dose monitoring. Spectroscopic techniques, such as Raman and fluorescence spectroscopy, offer real-time insights into tissue biochemistry, aiding in treatment response assessment and tumor characterization. However, despite such advantages of optical fiber sensors, challenges such as signal attenuation, calibration demands, and limited dynamic range remain. This paper further explores clinical application, technical limitations, and future directions, emphasizing multiplexing capabilities, integration and regulatory considerations, and trends in machine learning development. Collectively, these optical fiber sensing technologies show strong potential to improve the safety, accuracy, and adaptability of radiation therapy in personalized cancer care. Full article

Background: Dry Eye Disease (DED) is a multifactorial ocular disorder characterized by tear film instability, inflammation, oxidative stress, and ocular surface damage. Current therapeutic options often provide only temporary relief and are limited by poor patient compliance and inadequate drug retention at the ocular surface. Aim: This review aims to critically analyze the therapeutic potential of polyphenols and their nanoencapsulated formulations for the management of DED, focusing on pharmacological mechanisms, formulation strategies, and translational implications. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases using combinations of the following keywords: “dry eye disease,” “polyphenols,” “antioxidants,” “nanocarriers,” “ocular delivery,” and “bioavailability.” Studies published in English from 2000 to 2024 were considered. Inclusion criteria encompassed experimental, preclinical, and clinical studies evaluating polyphenol-based formulations for ocular application, while reviews without original data or studies unrelated to DED were excluded. Results: The analysis identified EGCG, curcumin, resveratrol, and quercetin as the most extensively investigated polyphenols, exhibiting antioxidant, anti-inflammatory, and cytoprotective activities through modulation of cytokines, reactive oxygen species, and immune signaling pathways. Nanoformulations such as lipid nanoparticles, micelles, and cyclodextrin complexes improved solubility, stability, ocular retention, and bioavailability, leading to enhanced therapeutic efficacy in preclinical DED models. Conclusions and Future Perspectives: Polyphenol-loaded nanocarriers represent a promising approach for improving the management of DED by enhancing local drug delivery and sustained release. However, further clinical studies are needed to assess long-term safety, scalability, and regulatory feasibility. Future research should focus on optimizing formulation reproducibility and exploring personalized nanotherapeutic strategies to overcome interindividual variability in treatment response. Full article

This review is focused on understanding the reasons why basal cell carcinoma (BCC), the most common, increasingly prevalent cancer, is classified as an “immune excluded” malignancy. It is, despite manifesting one of the highest tumor mutational burdens of any solid human malignancy, considered to be a biomarker of enhanced tumor immunogenicity and efficacy of tumor-targeted immunotherapy. Following a brief clinical overview, the balance of the review addresses important translational issues based on recent insights into the mechanisms underpinning immune exclusion/evasion in BCC. These include, firstly, the role of infectious agents and non-infectious potential causes of predisposition for and/or exacerbation of disease development and progression. Secondly, an overview of existing and emerging novel therapeutic strategies to ameliorate immune exclusion in BCC based on targeting several key immunosuppressive mechanisms. These are (i) inappropriate activation of the hedgehog signaling pathway (HHSP) due to formation of key driver mutations; (ii) interference with the presentation of tumor-specific antigens/neoantigens to cytotoxic T-cells; (iii) attenuation of the influx of anti-tumor natural killer cells; (iv) the recruitment and activation of immune suppressive regulatory T-cells; and (v) localized and systemic immune dysfunction achieved via elevated levels of soluble co-inhibitory immune checkpoint proteins (ICPs). The final section is focused on current and emerging pharmacologic and immune-based therapies. Full article

Geopolymers are inorganic aluminosilicate binders formed by alkali activation of reactive powders, offering a sustainable, low-carbon alternative to Portland cement. Their rapid setting and chemical durability make them well-suited for additive manufacturing (AM) in demanding environments, including underwater construction, where chemical stability is essential for both structural integrity and environmental safety. This study evaluates two metakaolin-based formulations designed for underwater extrusion, differing in activator chemistry and rheology control. Standardized leaching tests revealed alkaline but stable leachates with strong immobilization of most ions; major anions and total dissolved solids remained within regulatory thresholds. Limited exceedances were observed—soluble organic carbon in the NaOH-activated mix and arsenic/selenium in the waterglass–sand system—highlighting specific areas for mix improvement rather than fundamental limitations of the material. Complementary radioactivity screening confirmed activity concentration indices well below the regulatory limit, with measured radionuclide activities falling comfortably within exemption ranges. Together, the leaching and radioactivity results demonstrate that both formulations provide robust matrix integrity and environmental compatibility, while highlighting clear opportunities for mix design improvements to further minimize ecological risks. Full article

This paper examines how organizations and regions integrate digital transformation with environmental sustainability (“twin transition”). Based on 43 semi-structured expert interviews across 27 countries, we identify five empirically grounded insights. First, adoption is propelled by competitive pressure, external shocks, and rising regulatory and stakeholder demands. Second, success depends on internal capabilities—clear leadership vision and workforce skills—together with supportive regional innovation ecosystems. Third, deliberate technological synergies—especially digital twins for lifecycle optimization, Artificial Intelligence (AI)/analytics and Internet of Things (IoT) for monitoring, and blockchain for traceability—enable measurable gains in resource efficiency and environmental performance. Fourth, integration strengthens eco-innovation capacity, resilience to disruption, competitive positioning, and regional innovation dynamics. Fifth, persistent barriers remain; organizational silos, key performance indicators (KPIs) misalignment, rebound effects from digital infrastructures, and uneven regional capabilities. By linking enabling conditions, integration mechanisms, and barriers, the study advances theory and offers actionable guidance for managers and policymakers on realizing the twin transition, using descriptive counts to indicate salience within a purposive expert sample rather than to draw statistical inferences. Full article

Cuproptosis is a newly identified type of copper (Cu)-dependent programmed cell death (PCD), triggered when Cu directly interacts with the lipoylated components of the tricarboxylic acid (TCA) cycle, and it has shown significant antitumor potential. However, challenges such as insufficient Cu accumulation in tumor cells, systemic toxicity, and the lack of specific carriers for effectively inducing cuproptosis hinder its practical application. Inorganic nanoparticles (INPs) present a promising solution due to their unique ability to target specific areas, potential for multifunctional modification, and controlled release capabilities. Their distinctive physicochemical properties also enable the integration of synergistic multimodal cancer therapies. Therefore, utilizing INPs to induce cuproptosis represents a promising strategy for cancer treatment. This review systematically elucidates the regulatory mechanisms of Cu homeostasis and the molecular pathways underlying cuproptosis, thoroughly discusses current INP-based strategies designed to trigger cuproptosis, and comprehensively examines the multi-modal synergistic antitumor mechanisms based on cuproptosis. Finally, we also address the current challenges and future perspectives in developing clinically applicable nanoplatforms aimed at harnessing cuproptosis for effective cancer therapy. Full article

To enhance the nutritional value of sheep fat, high-melting-point solid fat (HSO) and low-melting-point liquid oil (LSO) were prepared from Altay sheep rump fat via solvent fractionation. The effects of HSO and LSO on lipid metabolism and intestinal health were evaluated in a mouse model. Results showed that HSO, rich in saturated fatty acids (SFA), induced obesity, dyslipidemia, and colonic inflammation in mice. These adverse effects were associated with the upregulation of hepatic lipid synthesis genes such as Sterol regulatory element-binding protein 1c (SREBP-1c) and Fatty acid synthase (FAS), as well as increased expression of pro-inflammatory cytokines including Tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) in the colon. In contrast, LSO, which was predominantly composed of unsaturated fatty acids (UFA), did not cause significant metabolic disorders. Instead, it promoted the upregulation of fatty acid oxidation-related genes such as Peroxisome proliferator-activated receptor alpha (PPARα) and Acyl-CoA oxidase 1 (Acox1), helped maintain intestinal microbial balance, and enhanced the production of beneficial short-chain fatty acids (SCFAs), particularly butyrate and propionate. In conclusion, solvent fractionation effectively modulates the fatty acid composition of sheep fat, thereby influencing lipid metabolism and inflammatory responses through the regulation of key gene expression and modulation of the gut microenvironment. Full article

The exceptional physicochemical properties of selenium nanoparticles (SeNPs) have led to their widespread development. The function of SeNPs is significantly influenced by their shape and particle size, which are in turn determined by the applied synthesis methods. This work presents a critical and comparative analysis of physical, chemical, and biosynthetic methods. The key point is to elaborate on how different methods precisely regulate the particle size, morphology, and stability that are crucial to their functional efficacy. This work emphasizes the importance of creating standardized protocols for characterizing SeNPs in order to make meaningful comparisons between the effectiveness of various studies. We further elucidate the underlying mechanisms of SeNPs’ anti-tumor, antioxidant, and antibacterial activities. A key novelty of this work lies in its systematic construction of a bridge between the synthesis, properties, functions, applications, and translational potential and its provision of a critical assessment. Finally, the review identifies and summarizes the principal challenges hindering clinical and commercial translation, including the imperative for standardized toxicological evaluation, scalable synthesis, and regulatory alignment. Full article

While stamen-focused research has predominantly examined flowering ornamental species, the tissue-specific regulatory mechanisms governing anthocyanin biosynthesis in potato stamens remain poorly understood. To characterize the tissue-specific regulatory mechanisms controlling anthocyanin biosynthesis in potato reproductive and storage organs, this investigation employed the red stamen mutant line ‘BF1811-8’ and the commercial cultivar ‘Atlantic’ as experimental models. Anthocyanin composition and quantification were determined using high-performance liquid chromatography (HPLC), while RNA-sequencing coupled with quantitative real-time PCR validation enabled comprehensive analysis of differential gene expression patterns within the anthocyanin biosynthetic pathway. Biochemical analysis revealed complete absence of anthocyanins across all examined tissues in ‘Atlantic’, whereas ‘BF1811-8’ exhibited tissue-specific anthocyanin profiles: stamens accumulated delphinidin and pelargonidin, while tuber skin and flesh primarily contained pelargonidin and peonidin. Gene ontology and KEGG pathway enrichment analysis of differentially expressed genes identified significant representation within secondary metabolism, flavonoid biosynthesis, and pigmentation processes. The transcription factors StMYB4 and StMYBA1 demonstrated positive regulatory roles in anthocyanin biosynthesis within tuber flesh and skin, respectively, while exhibiting coordinated expression with structural genes including CHS, DFR, ANS, and GST. Notably, StbHLH94 showed stamen-specific regulatory activity and demonstrated transcriptional co-regulation with 3GT. These findings provide crucial insights into the tissue-specific regulatory architecture governing potato anthocyanin biosynthesis, establishing a foundation for elucidating molecular mechanisms underlying tissue-specific pigmentation and advancing functional cultivar development. Full article

Panama, with nearly 3000 km of coastline and half its population living in coastal zones, faces high vulnerability to sea level rise, flooding, and extreme events. The most vulnerable areas include low-lying coastal provinces such as Panama, Colón, and Chiriquí. This review explores the use of sustainable concrete to address the effects of climate change in Panama towards coastal resilience. The methodology combined a bibliometric analysis using VOSviewer, a systematic literature review (2015–2025) of 99 sources including regulations and technical standards, and a socioeconomic SWOT analysis to assess adoption drivers and barriers. A 2050 permanent inundation map was examined to identify vulnerable areas, and an inventory of concrete-based protection structures was developed. The results highlight that concrete is already used in Panama for coastal resilience through structures such as breakwaters, dolos, and Xbloc units. However, as the country still needs to expand its coastal protection infrastructure, there is a crucial opportunity to implement lower-impact, sustainable concrete alternatives that minimize environmental burdens while ensuring long-term durability and performance. Sustainable options, including supplementary cementitious materials (SCMs), recycled aggregates, and CO₂ injection technologies, demonstrate strong mitigation potential, with national initiatives such as Vertua, Greentec, and Argos pozzolan offering early pathways. The conclusions emphasize the need to expand sustainable concrete applications, integrate nature-based solutions, and strengthen Panama’s regulatory and technical capacity to achieve resilient, low-carbon coastal infrastructure. Full article

Gene regulatory networks (GRN) govern cellular identity and function through precise control of gene transcription. Single-cell technologies have provided powerful means to dissect regulatory mechanisms within specific cellular states. However, existing computational approaches for modeling single-cell RNA sequencing (scRNA-seq) data often infer local regulatory interactions independently, which limits their ability to resolve regulatory mechanisms from a global perspective. Here, we propose a deep learning framework (Planet) based on diffusion models for constructing cell-specific GRN, thereby providing a systems-level view of how protein regulators orchestrate transcriptional programs. Planet jointly optimizes local network structures in conjunction with gene expression profiles, thereby enhancing the structural consistency of the resulting networks at the global level. Specifically, Planet decomposes GRN generation into a series of Markovian evolution steps and introduces a Triple Hybrid-Attention Transformer to capture long-range regulatory dependencies across diffusion time-steps. Benchmarks on multiple scRNA-seq datasets demonstrate that Planet achieves competitive performance against state-of-the-art methods and yields only a slight improvement over DigNet under comparable conditions. Compared with conventional diffusion models that rely on fixed sampling schedules, Planet employs a fast-sampling strategy that accelerates inference with only minimal accuracy trade-off. When applied to mouse-lung Cd8⁺Gzmk⁺ T cells, Planet successfully reconstructs a cell-type-specific GRN, recovers both established and previously uncharacterized regulators, and delineates the dynamic immunoregulatory changes that accompany ageing. Overall, Planet provides a practical framework for constructing cell-specific GRNs with improved global consistency, offering a complementary perspective to existing methods and new insights into regulatory dynamics in health and disease. Full article