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The scratch test is used as an experimental in vitro model of mechanical damage to primary neuronal cultures to study the mechanisms of cell death in damaged areas. The involvement of NMDA receptors in processes leading to delayed neuronal death, due to calcium dysregulation and synchronous mitochondrial depolarization, has been previously demonstrated. In this study, we explored the neuroregenerative potential of Pro-Gly-Pro (PGP)-an endogenous regulatory peptide with neuroprotective and anti-inflammatory properties and a mild chemoattractant effect. Mechanical injury to the primary neuroglial culture in the form of a scratch caused acute disruption of calcium homeostasis and mitochondrial functions. This was accompanied by neuronal death alongside changes in the profile of neuronal markers (BDNF, NSE and GFAP). In another series of experiments, under subtoxic doses of glutamate (Glu, 33 μM), delayed changes in [Ca 2+ ] i and ΔΨm, i.e., several days after scratch application, were more pronounced in cells in damaged neuroglial cultures. The percentage of cells that restored the initial level of [Ca 2+ ] i ( p < 0.05) and the rate of recovery of ΔΨm ( p < 0.01) were decreased compared with undamaged cells. Prophylactic application of PGP (100 μM, once) prevented the increase in [Ca 2+ ] i and the sharp drop in mitochondrial potential [ΔΨm] at the time of scratching. Treatment with PGP (30 μM, three or six days) reduced the delayed Glu-induced disturbances in calcium homeostasis and cell death. In the post-glutamate period, the surviving neurons more effectively restored the initial levels of [Ca 2+ ] i ( p < 0.001) and Ψm ( p < 0.0001). PGP also increased intracellular levels of BDNF and reduced extracellular NSE. In the context of the peptide's therapeutic effect, the recovery of the damaged neuronal network occurred faster due to reduced astrogliosis and increased migration of neurons to the scratch area. Thus, the peptide PGP has a neuroprotective effect, increasing the survival of neuroglial cells after mechanical trauma in vitro by reducing cellular calcium overload and preventing mitochondrial dysfunction. Additionally, the tripeptide limits the post-traumatic consequences of mechanical damage: it reduces astrogliosis and promotes neuronal regeneration.

This study investigates the potential of using sewage sludge and low-rank coal for the sustainable production of sulfuric acid, which can then be used for the hydrolysis of straw through ASPEN PLUS simulation. Pyrolysis and gasification processes were used to convert sewage sludge and low-rank coal into syngas, which were then purified and oxidized to produce H 2 SO 4 and NH 3 gas. The pyro-gasification enhanced syngas yield. The effects of key process parameters such as temperature, steam-to-biomass ratio, equivalence ratio, and feedstock composition on the yield and composition of syngas and H 2 SO 4 coupled with minor parameters like pressure were investigated. The simulation was conducted over the temperature and pressure range of 400 - 900°°C and 70 - 150 kPa respectively. While the steam-to-biomass ratio and equivalence ratio were respectively varied from 0.66 - 1.65 and 0.14 - 0.35. Part of the 1012.88 kg/h of H 2 SO 4 produced was used to hydrolyze straw, producing glucose as a valuable feedstock for biorefineries. About 3989.10 kg/h of NH 3 was produced. Results showed that the use of sewage sludge and low-rank coal as feedstocks for syngas production can be a sustainable and cost-effective alternative to traditional fossil fuels. The resulting H 2 SO 4 can also be used for various other applications, such as in the production of fertilizers and detergents. Overall, this study agrees with the literature, demonstrates the potential of integrating biomass and waste resources for the sustainable production of high-value chemicals and fuels, and contributes to the field of sustainable chemical and energy production while addressing environmental and economic considerations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Deficiency of adenosine deaminase 2 (DADA2) results in heterogeneous manifestations including systemic vasculitis and red cell aplasia. The basis of different disease phenotypes remains incompletely defined., Objective: We sought to further delineate disease phenotypes in DADA2 and define the mechanistic basis of ADA2 variants., Methods: We analyzed the clinical features and ADA2 variants in 33 patients with DADA2. We compared the transcriptomic profile of 14 patients by bulk RNA sequencing. ADA2 variants were expressed experimentally to determine impact on protein production, trafficking, release, and enzymatic function., Results: Transcriptomic analysis of PBMCs from DADA2 patients with the vasculitis phenotype or pure red cell aplasia phenotype exhibited similar upregulation of TNF, type I interferon, and type II interferon signaling pathways compared with healthy controls. These pathways were also activated in 3 asymptomatic individuals with DADA2. Analysis of ADA2 variants, including 7 novel variants, showed different mechanisms of functional disruption including (1) unstable transcript leading to RNA degradation; (2) impairment of ADA2 secretion because of retention in the endoplasmic reticulum; (3) normal expression and secretion of ADA2 that lacks enzymatic function; and (4) disruption of the N-terminal signal peptide leading to cytoplasmic localization of unglycosylated protein., Conclusions: Transcriptomic signatures of inflammation are observed in patients with different disease phenotypes, including some asymptomatic individuals. Disease-associated ADA2 variants affect protein function by multiple mechanisms, which may contribute to the clinical heterogeneity of DADA2., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Purpose: Lumbar spinal stenosis (LSS) is a condition affecting several hundreds of thousands of adults in the United States each year and is associated with significant economic burden. The current decision-making practice to determine surgical candidacy for LSS is often subjective and clinician specific. In this study, we hypothesize that the performance of artificial intelligence (AI) methods could prove comparable in terms of prediction accuracy to that of a panel of spine experts., Methods: We propose a novel hybrid AI model which computes the probability of spinal surgical recommendations for LSS, based on patient demographic factors, clinical symptom manifestations, and MRI findings. The hybrid model combines a random forest model trained from medical vignette data reviewed by surgeons, with an expert Bayesian network model built from peer-reviewed literature and the expert opinions of a multidisciplinary team in spinal surgery, rehabilitation medicine, interventional and diagnostic radiology. Sets of 400 and 100 medical vignettes reviewed by surgeons were used for training and testing., Results: The model demonstrated high predictive accuracy, with a root mean square error (RMSE) between model predictions and ground truth of 0.0964, while the average RMSE between individual doctor's recommendations and ground truth was 0.1940. For dichotomous classification, the AUROC and Cohen's kappa were 0.9266 and 0.6298, while the corresponding average metrics based on individual doctor's recommendations were 0.8412 and 0.5659, respectively., Conclusions: Our results suggest that AI can be used to automate the evaluation of surgical candidacy for LSS with performance comparable to a multidisciplinary panel of physicians., (© 2022. The Author(s).)