Formulation and administration timing of lipid derivatized JAK-inhibitor and corticosteroid modulate saRNA-LNP inflammation and expression.

Comprehensive studies of plasma pharmacokinetic and bone tissue distribution in rats to elucidate pharmacodynamic material basis of Psoraleae Fructus treating osteoporosis.

Saxitoxin induces progressive myocardial injury via disrupting calcium-dependent excitation-contraction coupling pathway: A biochemical, radiological, and histological evaluation.

Inhibiting the malignant proliferation is crucial for managing the cancer progression. NCAPG (Non-SMC condensin I complex subunit G) is a main component in cell proliferation, which is highly expressed in liver tumors and negatively correlated with the overall survival of hepatocellular carcinoma (HCC) patients. In this study, we identified bufalin as a molecular glue for the first time that specifically degraded NCAPG by coupling it to cathepsin V (CTSV). Distinguished from traditional PROTACs, bufalin served as a molecular glue with the distinct advantages of a smaller molecular weight and superior bioavailability. This degradation inhibited the proliferation of HCC cells by inducing G2/M phase cell cycle arrest at low doses (20-40 nM), but did not trigger the apoptosis signaling. Using co-immunoprecipitation and confocal microscopy, we confirmed the interaction between CTSV and NCAPG by bufalin. Knockdown of CTSV or NCAPG attenuated the anti-proliferation effects of bufalin in HCC cells. Cell cycle analysis also showed significantly reduced G2/M arrest in knockdown cells. The downstream proliferation regulators Cyclin D1 and CDK1 were also regulated by bufalin in a CTSV/NCAPG-dependent manner. Our study not only identified the CTSV-NCAPG complex as a novel therapeutic target but also discovered a potential molecular glue, bufalin, which exerts anti-proliferation effects through cell cycle regulation. These findings highlight the potential clinical translational value of bufalin as a promising, bioavailable therapeutic agent for the targeted treatment of liver cancer.

A low dose is better than no dose: Is it time to consider lowering the US minimum plateletpheresis yield?

Glycoprotein-specific transcriptional response contributes to differential vaccine protection against lethal Ebola virus infection.

Systematic pharmacology-guided analysis of the therapeutic mechanism of Sedum sarmentosum against chronic liver injury.

Effects of overall and modality-specific exercise dose on lower-limb functional mobility in middle-aged and older adults with stroke: A systematic review and bayesian dose-response meta-analysis.

Eastman Tritan™ copolyester, a novel plastic used as a replacement for bisphenols and manufactured utilizing three monomers, can be released from products, potentially entering biological fluids, and could exert estrogenic activity. Since neutrophils are inflammatory cells that express hormone receptors, we hypothesized that Tritan compounds could modulate neutrophil metabolism and function. Human neutrophils from the blood of healthy male and female donors were exposed in vitro to Tritan monomers, alone or combined with pro-inflammatory cytokines, and assessed for viability, metabolism, surface marker expression, and antimicrobial functions. Tritan compounds did not affect neutrophil viability but increased metabolic activity under inflammatory conditions. The production of CCL4/MIP-1β was reduced, while CXCL8/IL-8 was unchanged. Phagocytosis and reactive oxygen species production were altered in a dose-dependent manner, with the effect more pronounced in male neutrophils at lower doses and female neutrophils at higher doses. The expression of CD11b and CD16, adhesion and functional markers, was also modulated by Tritan monomers. These results indicate that Tritan and its monomers can alter neutrophil phenotype and function, potentially impairing host defence or contributing to dysregulated inflammation. These findings raise concerns about the safety of Tritan as an alternative plasticizer. Further research is needed to better understand the potential health risks of Tritan and its monomers, to help develop or update evidence-based regulations that protect public health.

Delivery science: Its increasing importance for the next generation of medicines.

Boric acid attenuates sepsis-induced cardiac injury through TLR4/mTOR modulation.

Suppressive effect of myristic acid on postprandial blood glucose elevation in healthy adults with high blood glucose levels: A double-blinded, randomized, placebo-controlled, parallel-group study.

IL-5 promotes airway remodeling in asthma by mediating epithelial-mesenchymal transition via the AKT/NLRP3 pathway.

The linear no-threshold hypothesis (commonly known as LNT) has received increasing criticism in recent years. LNT assumes that the damaging effects of ionizing radiation, that is, stochastic effects such as cancer and genetic or teratogenic effects, increase linearly with dose and without a lower dose threshold. However, statistically verified data on the relationship between radiation and effects are only obtained for the range above 100 mSv y -1 , which is why linear extrapolation downward is carried out for the range of low radiation doses, i.e., below 100 mSv y -1 . Today's radiation protection systems are based on this principle. To place radiation protection on a different basis (that is, no longer on the LNT hypothesis), a traffic light model is proposed. It uses natural radiation exposure as a reference but maintains the existing limits and everything in radiation protection that has proven effective. What does change, however, is the lower end of the optimization range, according to the ALARA recommendation. For the justification of today's levels of exceptions, the precautionary principle is applied.

Simultaneous saccharification and co-fermentation of dilute acid co-pretreated corn straw and tapioca starch with low enzyme dosage for enhanced lipid production by Cutaneotrichosporon oleaginosum

Swallowing-related outcomes and organ-at-risk dosimetry after proton versus photon radiotherapy in nasopharyngeal carcinoma.

Lipid-stabilized ICG nanoaggregates for the photodisruption of vitreous opacities.

The TEDDI trial tested the feasibility and reproducibility of deep-inspiration breath-hold (DIBH) in pediatric patients referred for radiotherapy. This report presents final results, including patient-reported outcomes (PRO) and dosimetric comparison of DIBH and free-breathing (FB). Pediatric patients able to perform three sequential breath-holds and potentially requiring thoracic or upper abdominal radiotherapy were recruited. DIBH training was during staging or planning computed tomography (CT) scanning, using external gating with an external marker and visual coaching. Each patient underwent planning CT in both DIBH and FB, generating two radiotherapy plans. DIBH was selected if it resulted in a lower overall dose to organs at risk. At two centers, patients evaluated their DIBH experience during training. Those treated in DIBH also completed three daily questions and extended questionnaires at the start, midpoint, and end of treatment, using yes/no and five-point Likert scales. Twenty-five patients (12 females/13 males, median age 15years, range: 9-17years) were enrolled across three centers. Eight received photon radiotherapy, five in DIBH. Of 13 eligible patients, 11 rated DIBH training, with 10 selecting "Really good" or "Good." Patients treated in DIBH reported feeling safe and comfortable. Dosimetric analysis showed clear heart and lung dose reductions with DIBH. FB patients had similar doses across both plans. The TEDDI trial demonstrated the feasibility and safety of DIBH in pediatric radiotherapy. High compliance with the procedure and favorable dosimetric outcomes support the use of DIBH to reduce long-term toxicity risks in this population.

Ivermectin (IVM) is a cornerstone of nematode control. However, its efficacy is increasingly compromised by emerging resistance in target parasites. P-glycoproteins (Pgps), which mediate drug efflux, and amphid neuron defects, characterized by a dye-filling defective (Dyf) phenotype, may both contribute to IVM resistance in Caenorhabditis elegans, but their respective roles and potential connection remain to be clarified. Here, we investigated these mechanisms in three independently evolved Caenorhabditis elegans lineages exposed to stepwise IVM selection. These populations, although distinct, converged over time to a comparable and stabilized high level of IVM resistance. Endpoint transcriptomes revealed fluctuations in the expression of several pgp, overexpressed in one lineage only, suggesting that sustained pgp upregulation is not a conserved feature of stable resistance. Consistently, neither short-term exposure to IVM nor long-term drug pressure selection elicited strong transcriptional induction. Nevertheless, we uncovered a transient surge of several pgp transcripts during the early selection process of the worms exposed to low doses of IVM. We speculate this relates to an early pgp-dependent tolerance mechanism in the dynamic adaptation program to IVM. Beyond an initial pgp-based response, our expanded RNA-seq analysis across lineages revealed a conserved enrichment for ciliary/neuronal pathways including genes expressed in amphid/phasmid, indicating remodeling of the chemosensory/ciliary network as resistance intensifies. All resistant lines also converged on the Dyf phenotype that emerged during selection at stages coinciding with sharp gains in IVM tolerance, implicating amphid structure/function in the establishment of durable resistance. Together, these data reconcile heterogeneous literature on PGPs by decoupling transient, context-dependent pgp activation from long-term maintenance of resistance, and are consistent with previous work showing ciliary pathways as common denominators of IVM resistance. We propose a two-phase associative model in which early PGP-mediated tolerance precedes the emergence of ciliary/amphidial signatures and a Dyf phenotype during selection that durably reduces susceptibility.

pH-responsive polymeric-peptide complex enhances tumor immunogenic cell death by membrane disruption.