Search Results (49)

Oxidative stress destabilizes microRNA homeostasis in the retinal pigment epithelium (RPE), driving apoptosis and the epithelial-to-mesenchymal transition, which contribute to age-related macular degeneration. We investigated whether Quantum Molecular Resonance (QMR^®) electrostimulation, alone or combined with Patient Blood-Derived (PBD) secretoma, can reprogram the RPE miRNome and mitigate stress-induced damage. Human ARPE-19 cells were exposed to tert-butyl-hydroperoxide and treated with QMR^®, PBD secretome, or their combination. The deep sequencing of small RNAs at 24 h and 72 h, followed by differential expression and pathway enrichment analyses, delineated treatment-driven miRNA signatures. Oxidative stress deregulated > 50 miRNAs, enriching pro-apoptotic, fibrotic, and inflammatory pathways. QMR^® restored roughly 40% of these miRNAs and upregulated additional cytoprotective species such as miR-590-3p, a known regulator of the NF-κB and NLRP3 pathways according to validated target databases. While these observations suggest the potential involvement of inflammatory and stress-related cascades, functional assays will be required to directly confirm such effects. Secretome treatment preferentially increased anti-inflammatory miR-146a-5p and regenerative miR-204-5p while suppressing pro-fibrotic let-7f-5p. Combined QMR^® + secretome triggered the broadest miRNA response, normalizing over two-thirds of stress-altered miRNAs. These changes are predicted to influence antioxidant, anti-apoptotic, and anti-fibrotic pathways, although they did not translate into additional short-term cytoprotection compared with QMR^® alone. These data indicate that QMR^® and PBD secretome modulate complementary miRNA programs that converge on stress response networks. This broader molecular reprogramming may reflect regulatory complementarity, but functional validation is needed to determine whether it provides benefits beyond those observed with QMR^® alone. These findings offer molecular insights into potential non-invasive, cell-free strategies for retinal degeneration, although in vivo validation will be required before any clinical translation to Age-Related Macular Degeneration (AMD) therapy. Full article

The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article

Drought stress negatively affects plant metabolism and growth, triggering complex defence mechanisms to limit damage. This study evaluated the effectiveness of a single foliar application of 1 mM L-proline (Pro) in winter wheat (Triticum aestivum L., cv. Bohemie) in two separate experiments differing in the time interval between application and drought—7 days (experiment 1) and 35 days (experiment 2). Net photosynthetic rate (A), transpiration rate (E), stomatal conductance (g_s), leaf water potential (Ψw), intrinsic water use efficiency (WUE_i), endogenous proline content (Pro), malondialdehyde content (MDA), and maximum quantum yield of photosystem II (F_v/F_m) were measured. In experiment 1, drought markedly reduced net photosynthetic rate, transpiration rate, stomatal conductance, and leaf water potential in both drought-stressed treatments, namely, without priming plants (S) and with Pro priming plants (SPro). Pro and MDA content increased under stress. Higher E and g_s in the SPro treatment indicated more effective stomatal regulation and a distinct water use strategy. Pro content was significantly lower in SPro compared to S, whereas differences in MDA levels between these treatments were not statistically significant. The second drought period (D2) led to more pronounced limitations in gas exchange in both S and SPro. Enhanced osmoregulation was reflected by lower Ψw (S < SPro) and higher Pro accumulation in S (S > SPro). The effect of exogenous Pro persisted in the form of reduced endogenous Pro synthesis and improved photosystem II protection. Rehydration of stressed plants restored all monitored physiological parameters, and Pro-treated plants exhibited a more efficient recovery of gas exchange. Experiment 2 demonstrated a long-lasting priming effect that improved the preparedness of plants for future drought events. In the SPro treatment, this stress memory supported more efficient osmoregulation, reduced lipid peroxidation, improved protection of photosystem II integrity, and a more effective restart of gas exchange following rehydration. Our findings highlight the potential of exogenous proline as a practical tool for enhancing crop resilience to climate-induced drought stress. Full article

For the interaction of angiotensin II (AngII) with AngII type 1 receptors (AT₁R), two potential proton hopping pathways have been identified, each associated with distinct physiological outcomes. The octapeptide AngII (Asp¹-Arg²-Val³-Tyr⁴-Ile⁵-His⁶-Pro⁷-Phe⁸) appears to form a charge relay system (CRS) in solution in which the C-terminal carboxylate abstracts a proton from the His⁶ imidazole group, which, in turn, abstracts a proton from the Tyr⁴ hydroxyl (OH) group, creating a tyrosinate anion. When AngII binds to the AT₁R, the CRS can be reconstituted with D281 of the receptor taking up the role of the Phe⁸ carboxylate in the tripartite interaction, whilst the Phe⁸ carboxylate forms a salt bridge with K199 of the receptor. As a consequence, the Tyr⁴ OH of AngII is positioned with accessibility to either the Phe⁸ carboxylate (bound to K199) or the His⁶ imidazole (activated by D281), thereby creating a potential gating mechanism for AT₁R receptor signaling. This study summarizes evidence based on structure activity data for various analogs wherein Tyr⁴ OH interaction with His⁶ imidazole (CRS formation) leads to G protein sequestration and vasoconstriction, whereas Tyr⁴ OH interaction with Phe⁸ carboxylate (bound to K199) engenders arrestin-mediated vasodilation and receptor desensitization. These findings, combined with quantum mechanical (semiempirical) calculations of CRS proton transfer presented herein, provide insights for the therapeutic targeting of angiotensin receptor blockers (sartans) and the development of second-generation drugs (bisartans). Full article

The importance of sustainable polymers has increased greatly in the last years since most polymers are derived from non-renewable sources. Sustainable polymers (i.e., biopolymers) such as natural rubber (NR) are proposed as a solution for this concern. A comparative study between NR and deproteinized NR (DPNR) was carried out to elucidate the role of proteins on the network formation and degradation of peroxide cross-linked NR using time-domain NMR experiments. The ¹H multiple-quantum (MQ) NMR experiments provided information on the cross-link density and its spatial distribution, while the actual fraction of non-coupled network defects was obtained by exploiting the Hahn echo approach measured on swollen samples. The results showed that proteins influenced the network formation during the vulcanization process of NR, leading to a higher number of non-elastic network defects and promoting the creation of additional cross-links with a broader spatial distribution. The formation of network heterogeneities in different length scales deeply influences the mechanical properties of NR samples. On the other hand, the proteins showed a pro-oxidant activity on the degradation behavior by accelerating the degradation process of peroxide cross-linked NR. Full article

The growing need for sustainable energy solutions has propelled the development of Hybrid Renewable Energy Systems (HRESs), which integrate diverse renewable sources like solar, wind, biomass, geothermal, hydropower and tidal. This review paper focuses on balancing economic, environmental, social and technical criteria to enhance system performance and resilience. Using comprehensive methodologies, the review examines state-of-the-art algorithms such as Multi-Objective Particle Swarm Optimization (MOPSO) and Non-Dominated Sorting Genetic Algorithm II (NSGA-II), alongside Crow Search Algorithm (CSA), Grey Wolf Optimizer (GWO), Levy Flight-Salp Swarm Algorithm (LF-SSA), Mixed-Integer Linear Programming (MILP) and tools like HOMER Pro 3.12–3.16 and MATLAB 9.1–9.13, which have been instrumental in optimizing HRESs. Key findings highlight the growing role of advanced, multi-energy storage technologies in stabilizing HRESs and addressing the intermittency of renewable sources. Moreover, the integration of metaheuristic algorithms with machine learning has enabled dynamic adaptability and predictive optimization, paving the way for real-time energy management. HRES configurations for cost-effectiveness, environmental sustainability, and operational reliability while also emphasizing the transformative potential of emerging technologies such as quantum computing are underscored. This review provides critical insights into the evolving landscape of HRES optimization, offering actionable recommendations for future research and practical applications in achieving global energy sustainability goals. Full article

The thermodynamic study of protein folding shows the generation of a narrow range of ΔG° values, as a net result of large changes in the ΔH° and TΔS° values of the folding process. The obvious consequence of this narrow range of values is that a linear enthalpy–entropy relationship, showing apparent enthalpy–entropy compensation (EEC), is clearly observed to be associated with the study of protein folding. Herein, we show the ΔH°, TΔS°, and ΔG° values for a set of 583 data from protein folding processes, at various temperatures, as calculated by using the Gibbs–Helmholtz equations. This set of thermodynamic data was calculated from the melting temperature (Tm), the melting enthalpy (ΔHm), and the change in heat capacity (ΔCp°) values, all of them associated with the heat-induced protein unfolding processes and included in the ProTherm Data Base. The average values of enthalpy (ΔH°av), entropy (TΔS°av), and free energy (ΔG°av) for the folding process were calculated within the range of temperature from 0 °C to the average value of Tm. The values and temperature dependency of TΔS°av within this temperature range are practically equal to those corresponding to ΔH°av, while ΔG°av remains small and displaying a curve with a minimum at about 10 °C and a value of ΔG° = −30.9 kJ/mol at the particular temperature of 25 °C. The large negative value of TΔS°av, together with the also large and negative value of ΔCp°av, suggests large conformational changes and important EEC, thus causing the small average value of ΔG° for protein folding, which is enough to guarantee both protein stability and molecular flexibility to allow for adaptation to the chemical potentials of the environment. Our analysis suggests that EEC may be the quantum-mechanical evolutive mechanism to make functional proteins adaptative to environmental temperature and metabolite concentrations. The analysis of protein folding data, compared with those of protein–ligand interaction, allows us to suggest strategies to overcome EEC in the design of new drugs. Full article

Fruits and vegetables play a crucial role in addressing food security challenges posed by the growing global population. Citrus fruits are among the most widely cultivated crops worldwide; however, their production is steadily declining due to climate change. Among the various biotic and abiotic stresses affecting citrus production, water scarcity caused by climate change stands out as a significant issue. Interestingly, the rhizosphere of citrus plants is home to beneficial fungi known as arbuscular mycorrhizal fungi (AMF). AMF have been shown to enhance the growth and development of host plants. They also improve the plants’ tolerance to various stresses and enhance soil structure. This study aimed to evaluate the response of two different citrus rootstocks—Rangpur lime and Carrizo citrange—when subjected to three mycorrhizal treatments, namely, AMF+ (inoculated with AMF), AMF- (treated with fungicide to eliminate AMF), and a control (naturally occurring AMF), under conditions of water deficit. The results indicated that the AMF+ treatment had a significant positive effect on both rootstock genotypes compared to the AMF- treatment. Physiological attributes such as photosynthesis, stomatal conductance, transpiration, non-photochemical quenching, and both dark and light quantum yield exhibited significantly smaller declines under water deficit conditions in AMF+ plants compared to those in the AMF- and control groups. Conversely, stress indicators—such as malondialdehyde (MDA) and hydrogen peroxide (H₂O₂)—increased significantly in the AMF- treatment compared to AMF+. Additionally, the increase in antioxidative enzymes (superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APx) and osmotic adjustment (proline (PRO)) was more pronounced in the AMF+ treatment in the leaves and roots of both citrus rootstocks. In conclusion, the findings suggest that the presence and application of AMF in citrus roots may enhance the plants’ ability to cope with water scarcity more effectively. Full article

The rapid evolution of mobile and optical communication technologies is driving the transition from 5G to 6G networks. This transition inevitably brings about changes in authentication scenarios, as new security demands emerge that go beyond the capabilities of existing frameworks. Therefore, it is necessary to address these evolving requirements and the associated key challenges: ensuring Perfect Forward Secrecy (PFS) to protect communications even if long-term keys are compromised and integrating Post-Quantum Cryptography (PQC) techniques to defend against the threats posed by quantum computing. These are essential for both radio and optical communications, which are foundational elements of future 6G infrastructures. The DMRN Protocol, introduced in 2022, represents a major advancement by offering both PFS and PQC while maintaining compatibility with existing 3rd Generation Partnership Project (3GPP) standards. Given the looming quantum-era challenges, it is imperative to analyze the protocol’s security architecture through formal verification. Accordingly, we formally analyze the DMRN Protocol using SVO logic and ProVerif to assess its effectiveness in mitigating attack vectors, such as malicious or compromised serving networks (SNs) and home network (HN) masquerading. Our research found that the DMRN Protocol has vulnerabilities in key areas such as mutual authentication and key exchange. In light of these findings, our study provides critical insights into the design of secure and quantum-safe authentication protocols for the transition to 6G networks. Furthermore, by identifying the vulnerabilities in and discussing countermeasures to address the DMRN Protocol, this study lays the groundwork for the future standardization of secure 6G Authentication and Key Agreement protocols. Full article

Phycocyanin (PC) is a naturally occurring green pigment in Spirulina. It was extracted by ultrasonic extraction using green technology, and its structure was studied using IR- and NMR-spectroscopy. Spectral data confirmed the PC structure. This study also involves an in silico assessment of the diverse applications of green pigment PC. Utilizing QSAR, PreADME/T, SwissADME, and Pro-Tox, this study explores the safety profile, pharmacokinetics, and potential targets of PC. QSAR analysis reveals a favorable safety profile, with the parent structure and most metabolites showing no binding to DNA or proteins. PreADME/T indicates low skin permeability, excellent intestinal absorption, and medium permeability, supporting oral administration. Distribution analysis suggests moderate plasma protein binding and cautious blood–brain barrier permeability, guiding formulation strategies. Metabolism assessments highlight interactions with key cytochrome P450 enzymes, influencing drug interactions. Target prediction analysis unveils potential targets, suggesting diverse therapeutic effects, including cardiovascular benefits, anti-inflammatory activities, neuroprotection, and immune modulation. Based on the in silico analysis, PC holds promise for various applications due to its safety, bioavailability, and potential therapeutic benefits. Experimental validation is crucial to elucidate precise molecular mechanisms, ensuring safe and effective utilization in therapeutic and dietary contexts. DFT calculations, including geometry optimization, MEP analysis, HOMO-LUMO energy surface, and quantum reactivity parameters of the PC compound, were obtained using the B3LYP/6–311G(d,p) level. This integrated approach contributes to a comprehensive understanding of PC’s pharmacological profile and informs future research directions. Full article

The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro-β³-HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of L-amino acids by D-amino acids (a series of peptides denoted as P01–P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[D-Pro-Pro-β³-HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro-D-β³-HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations. Full article

Nanotechnology-enabled pesticide delivery systems have been widely studied and show great prospects in modern agriculture. Nanodelivery systems not only achieve the controlled release of agrochemicals but also possess many unique characteristics. This study presents the development of a pH-responsive pesticide nanoformulation utilizing hollow mesoporous silica nanoparticles (HMSNs) as a nanocarrier. The nanocarrier was loaded with the photosensitive pesticide prochloraz (Pro) and then combined with ZnO quantum dots (ZnO QDs) through electrostatic interactions. ZnO QDs serve as both the pH-responsive gatekeeper and the enhancer of the pesticide. The results demonstrate that the prepared nanopesticide exhibits high loading efficiency (24.96%) for Pro. Compared with Pro technical, the degradation rate of Pro loaded in HMSNs@Pro@ZnO QDs was reduced by 26.4% after 24 h ultraviolet (UV) exposure, indicating clearly improved photostability. In a weak acidic environment (pH 5.0), the accumulated release of the nanopesticide after 48 h was 2.67-fold higher than that in a neutral environment. This indicates the excellent pH-responsive characteristic of the nanopesticide. The tracking experiments revealed that HMSNs can be absorbed by rice leaves and subsequently transported to other tissues, indicating their potential for effective systemic distribution and targeted delivery. Furthermore, the bioactivity assays confirmed the fungicidal efficacy of the nanopesticide against rice blast disease. Therefore, the constructed nanopesticide holds great prospect in nanoenabled agriculture, offering a novel strategy to enhance pesticide utilization. Full article

Cardiovascular diseases (CVDs) represent a significant challenge in global health, demanding advancements in diagnostic modalities. This review delineates the progressive and restrictive facets of nanomaterial-based biosensors in the context of detecting N-terminal pro-B-type natriuretic peptide (NT-proBNP), an indispensable biomarker for CVD prognosis. It scrutinizes the escalation in diagnostic sensitivity and specificity attributable to the incorporation of novel nanomaterials such as graphene derivatives, quantum dots, and metallic nanoparticles, and how these enhancements contribute to reducing detection thresholds and augmenting diagnostic fidelity in heart failure (HF). Despite these technological strides, the review articulates pivotal challenges impeding the clinical translation of these biosensors, including the attainment of clinical-grade sensitivity, the substantial costs associated with synthesizing and functionalizing nanomaterials, and their pragmatic deployment across varied healthcare settings. The necessity for intensified research into the synthesis and functionalization of nanomaterials, strategies to economize production, and amelioration of biosensor durability and ease of use is accentuated. Regulatory hurdles in clinical integration are also contemplated. In summation, the review accentuates the transformative potential of nanomaterial-based biosensors in HF diagnostics and emphasizes critical avenues of research requisite to surmount current impediments and harness the full spectrum of these avant-garde diagnostic instruments. Full article

Proteogenomics is a recently developed omics application, adding enhancing the sensitivity of proteomics, and thus making possible the detection of proteome markers in very tiny amounts of samples. Even if the filed developed only in the last 10 years, the technology is very intensely applied in clinical diagnostics, and more recently, efforts are made to use it in non-clinical, in vitro and in vivo studies. The aim of this study was to investigate the applicability of single-plex and multiplex assays in the evaluation of proteome changes generated in vitro by the exposure to several standard compounds. The extracts demonstrated weak cytotoxic effects. The detection of cytokines Performing the same assays on tissue lysates permitted only the detection of low levels of cytokines. Full article

Natural products such as domestic herbal drugs which are easily accessible and cost-effective can be used as a complementary treatment in mild and moderate COVID-19 cases. This study aimed to detect and describe the efficiency of phenolics detected in the galangal–cinnamon mixture in the inhibition of SARS-CoV-2’s different protein targets. The potential antiviral effect of galangal–cinnamon aqueous extract (GCAE) against Low Pathogenic HCoV-229E was assessed using cytopathic effect inhibition assay and the crystal violet method. Low Pathogenic HCoV-229E was used as it is safer for in vitro laboratory experimentation and due to the conformation and the binding pockets similarity between HCoV-229E and SARS-CoV-2 M^Pro. The GCAE showed a significant antiviral effect against HCoV-229E (IC₅₀ 15.083 µg/mL). Twelve phenolic compounds were detected in the extract with ellagic, cinnamic, and gallic acids being the major identified phenolic acids, while rutin was the major identified flavonoid glycoside. Quantum-chemical calculations were made to find molecular properties using the DFT/B3LYP method with 6-311++G(2d,2p) basis set. Quantum-chemical values such as EHOMO, ELUMO, energy gap, ionization potential, chemical hardness, softness, and electronegativity values were calculated and discussed. Phenolic compounds detected by HPLC-DAD-UV in the GCAE were docked into the active site of 3 HCoV-229E targets (PDB IDs. 2ZU2, 6U7G, 7VN9, and 6WTT) to find the potential inhibitors that block the Coronavirus infection pathways from quantum and docking data for these compounds. There are good adaptations between the theoretical and experimental results showing that rutin has the highest activity against Low Pathogenic HCoV-229E in the GCAE extract. Full article