Search Results (7)

The ongoing threat of viral pandemics such as COVID-19 highlights the urgent need for novel antiviral therapeutics targeting conserved viral proteins. In this study, peptides of 10–30 kDa derived from the marine diatom Phaeodactylum tricornutum were identified as potential inhibitors of SARS-CoV-2 main protease (Mpro), a key enzyme in viral replication. Peptides less than 60 amino acids in length were retrieved from the UniProt database and aligned with reference antiviral sequences using the Biopython pairwise2 algorithm. Six candidates were selected for structural modeling using AlphaFold2 and Swiss-Model, followed by molecular docking using ClusPro2. LigPlot+ was used to assess molecular interactions, while NetMHCpan 4.1 and AVPpred evaluated immunogenicity and antiviral potential, respectively. Molecular dynamics simulations over 100 ns were conducted using OpenMM. These peptides demonstrated stable binding interactions with key catalytic residues of Mpro. Specifically, peptide A0A8J9SA87 interacted with Cys145 and Glu166, while peptide A0A8J9SDW0 exhibited interactions with His41 and Phe140, both of which are known to be essential for Mpro inhibition. Although peptide A0A8J9X3P8 also interacted with catalytic residues, it exhibited greater structural fluctuations during molecular dynamics simulations and achieved lower AVPpred scores, suggesting lower overall antiviral potential. Therefore, A0A8J9SA87 and A0A8J9SDW0 were identified as the most promising candidates. Molecular dynamics simulations further supported the high structural stability of these peptide-Mpro complexes over a 100 ns timescale, reinforcing their potential as effective inhibitors. These findings support P. tricornutum as a valuable source of antiviral peptides and demonstrate the feasibility of in silico pipelines for identifying therapeutic candidates against SARS-CoV-2. Full article

Stress and sleep share a reciprocal relationship, where chronic stress often leads to sleep disturbances that worsen neurodegenerative and psychiatric conditions. Non-neuronal cells, particularly astrocytes and microglia, play critical roles in the brain’s response to stress and the regulation of sleep. Astrocytes influence sleep architecture by regulating adenosine signaling and glymphatic clearance, both of which can be disrupted by chronic stress, leading to reduced restorative sleep. Microglia, activated under stress conditions, drive neuroinflammatory processes that further impair sleep and exacerbate brain dysfunction. Additionally, the gut–brain axis mediates interactions between stress, sleep, and inflammation, with microbial metabolites influencing neural pathways. Many of these effects converge on the disruption of synaptic processes, such as neurotransmitter balance, synaptic plasticity, and pruning, which in turn contribute to the pathophysiology of neurodegenerative and psychiatric disorders. This review explores how these cellular and systemic mechanisms contribute to stress-induced sleep disturbances and their implications for neurodegenerative and psychiatric disorders, offering insights into potential therapeutic strategies targeting non-neuronal cells and the gut–brain axis. Full article

Background: D-glucose (dextrose) is used as a 5000–25,000 mg% solution in the injection-based pain therapy known as dextrose prolotherapy (DPT). The number of peer-reviewed clinical trials supporting its use is growing. However, the mechanism of action is unknown, limiting further research. A commonly expressed theory is that hyperosmotic dextrose injection induces inflammation, initiating a healing-specific inflammatory cascade. In vitro study models have used continuous exposure to high concentration dextrose. But the rate of dextrose clearance after intra-articular injection, and, therefore, the duration of exposure of tissues to any particular dextrose concentration, remains unknown. We therefore determined the rate of dextrose concentration diminution in one human participant’s knees after intra-articular dextrose knee injection. Method: In this pre–post N-of-1 study, the first author (KDR), a well 70-year-old male without knee-related pathology, injected his own knees with 30 mL of 12,500 mg% dextrose on three occasions; performed serial aspirations of 1.2 mL of intra-articular fluid from 7 to 360 min post-injection; and assessed synovial dextrose concentration. Dextrose clearance kinetics were determined using Minitab and GraphPad Prism software. Results: Dextrose concentration dropped rapidly in all three trials, approximating an exponential or steep S curve. A third order chemical reaction pattern was found, suggesting factors other than dilution or glucose transporter activity, such as rapid diffusion of dextrose across the synovial membrane, may have contributed to the rapid drop in dextrose concentration. Conclusion: This pre-post N-of-1 study shows that, after intraarticular injection of 30 mL of 12,500 mg% dextrose injection into a well knee, the concentration of dextrose diminished rapidly, suggesting that intra-articular cells, tissue, and anatomic structures are exposed to an initially high dextrose concentration for a very short time. This likely affects the mechanism of action of DPT and should inform in vitro study methods. Full article

The protection of first responders from radioactive contamination with alpha emitters that may result from a radiological accident is of great complexity due to the short range of alpha particles in the air of a few centimeters. To overcome this issue, for the first time, a system mounted on a UAS for the near-real-time remote measurement of alpha particles has been developed, tested, and calibrated. The new system, based on an optical system adapted to be installed on a UAS in order to measure the UV-C fluorescence emitted by alpha particles in the air, has been tested and calibrated, carried out in the laboratory and in field experiments using UV-C LEDs and ²⁴¹Am sources. In experimental flights, the probability of detecting a point source was determined to be approximately 60%. In the case of a surface extended source, a detection efficiency per unit surface activity of 10 counts per second per MBq cm⁻² was calculated. A background count rate of UV-C of around 26 ± 28 s⁻¹ for an integration time of 0.1 s was measured during flights, which led to a decision threshold surface activity of 5 MBq cm⁻². Full article

Background: Neurocytokines may upregulate or downregulate neuropathic pain. We hypothesized that dextrose (D-glucose) injections for therapeutic purposes (dextrose prolotherapy: DPT) in painful knee osteoarthritis (KOA) would favorably affect synovial-fluid neurocytokine concentrations. Methods: Twenty participants with grade IV symptomatic KOA received synovial-fluid aspiration followed by dextrose or simulated dextrose injections, followed by the reverse after one week. All participants then received open-label dextrose injections monthly for 6 months, with serial assessments of walking pain at 20 min for 9 months, as well as synovial-neurocytokine-concentration measurements (calcitonin gene-related peptide, substance P (SP), and neuropeptide Y (NPY)) at one week and three months. Results: Clinically important analgesia was observed at 20 min and for 9 months post dextrose injection. One -week synovial-fluid SP concentration rose by 111% (p = 0.028 within groups and p = 0.07 between groups) in the dextrose-injected knees compared to synovial-fluid aspiration only. Three-month synovial-fluid NPY concentration dropped substantially (65%; p < 0.001) after open-label dextrose injection in all knees. Conclusions: Prompt and medium-term analgesia after intra-articular dextrose injection in KOA was accompanied by potentially favorable changes in synovial-fluid neurocytokines SP and NPY, respectively, although these changes were isolated. Including neurocytokines in future assessments of DPT to elucidate mechanisms of action is recommended. Full article

The radiation flux distributions produced by the concentrating solar systems used to produce thermal/electrical power are usually non-homogeneous. This results in non-uniform temperature distributions on the solar receivers, causing adverse effects on the system’s overall performance. An approach to better understand the problem is to study the surfaces around the focal zone where the radiation density is homogeneous (isosurfaces), generating them from experimental data. For this, it is necessary to superimpose built volumes of the different irradiance levels using parallel planes in different directions from the focal point of a concentrator. These volumes are known as effective volumes. This study presents the model used to generate effective volume produced by a point focus concentrator, comparing it with experimental results in a direction perpendicular to the focal axis. The effective volumes were developed considering a global optical error of the system of 2.8 mrad. The set of methods used to generate effective volumes has not been previously presented in the literature. The theoretical-experimental research consisted of the combination of the camera-target method and the simulations by the ray-tracing technique. The results showed effective volumes with the highest value of 10 MW/m² and the lowest value of 4.5 MW/m². Full article

Continuous infusions of levodopa directly into the duodenum-yeyunum is an effective therapy to reduce daily off time in an advanced stage of Parkinson's disease, but it is not without complications, particularly device related problems. We present our experience in three Spanish hospitals with these complications, including a severe case with migration, several decubitus ulcers, and one case of perforation of the bowel and finally death. Full article