Geochemical characteristics and the organic matter enrichment of the Upper Ordovician Tanjianshan Group, Qaidam Basin, China

Earlier researchers have examined the interaction between organic matter (OM) and metals, but the paragenesis of anthraxolite and mechanism enrichment of vanadium (V) need further study. Our recent geological field survey discovered that anthraxolite contains a substantial amount of V in the Member “a” of the Tanjianshan Group, Upper Ordovician in the northern margin of the Qaidam Basin. Different organic geochemical studies (fluid inclusions, zircon U–Pb dating, and petrochemistry) were conducted to examine the origin and evolution of anthraxolite, as well as the enrichment of V. The extractable organic matter (EOM) content of anthraxolite is low, while it contains a high amount of non-hydrocarbon and asphaltene. Anthraxolite is over-mature with its equivalent vitrinite reflectance being up to 4.9%. Anthraxolite is sourced from mudstone of Member “a” of the Tanjianshan Group. There were two hydrocarbon charging phases: (i) Late Devonian; and (ii) Carboniferous. Multiple magmatic thermal events took place after the Late Devonian period, resulting in hydrocarbon fluid cracking, metamorphism, and finally the formation of anthraxolite. Marine hot water deposition was irrelevant to enrichment of V. It is inferred that V originated during biological and biochemical processes, then migrated and accumulated with hydrocarbon formation and evolution, and finally enriched in anthraxolite.

Anthraxolite Evolution and Vanadium Enrichment Mechanism in the Tanjianshan Group, Upper Ordovician in the Northern Qaidam Basin

Abstract Alzheimer's disease (AD) is a neurodegenerative disease with high incidence and widespread attention. There is currently no clear clarification of the pathogenesis. However, ORMDL3 causes ferroptosis in AD, and the potential mechanisms remain unclear. So, this study explore the function of ORMDL3 on ferroptosis in AD and its potential regulatory mechanisms. APPswe/PS1dE9 mice and C57BL/6 mice were induced into the mice model. The murine microglial BV‐2 cells also were induced into the vitro model. In serum samples of AD patients, ORMDL3 mRNA expression levels were upregulated. The serum ORMDL3 levels expression was positively related to the ADL score or MoCA score in AD patients. The serum ORMDL3 expression level was positively related to MMSE score or Hcy levels in AD patients. The mRNA expression of ORMDL3 in the hippocampal tissue of the mice model of AD was upregulated at one, four and eight months. The protein expression of ORMDL3 was upregulated in the mice model of AD. ORMDL3 promoted Alzheimer's disease, and increased oxidative response and ferroptosis in a model of AD. PERK/ATF4/HSPA5 pathway is one important signal pathway for the effects of ORMDL3 in a model of AD. Collectively, these data suggested that ORMDL3 promoted oxidative response and ferroptosis in a model of AD by the PERK/ATF4/HSPA5 pathway, which might be a novel target spot mechanism of ferroptosis in AD and may serve as a regulator of AD‐induced ferroptosis.

The inhibition of ORMDL3 prevents Alzheimer's disease through ferroptosis by PERK/ATF4/HSPA5 pathway

Aim Doxorubicin (DOX) has long been criticized for its cardiotoxicity, yet one cannot overlook its hepatotoxicity. Deoxyschizandrin (Deo) is a type of monomer used in traditional Chinese medicine that has a powerful anti-inflammatory action and is frequently used to treat a variety of inflammatory diseases. However, its therapeutic effect on DOX-induced hepatotoxic inflammatory reactions is still unknown. Materials and Methods In this study, DOX was used to induce hepatotoxicity in rats, and the effects of Deo on hepatotoxicity and hepatic inflammation were investigated. Results The results show that Deo protects liver function by inhibiting PETN, which regulates DOX-induced liver inflammation. Conclusion The anti-inflammatory effect of Deo in DOX-induced hepatotoxicity is attributed to the inhibition of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and the increase in AKT phosphorylation.

https://doi.org/10.1177/09731296231165593

Deoxyschizandrin Inhibits PTEN to Regulate Inflammation in Doxorubicin-induced Hepatotoxicity

Pyroptosis, a lytic and inflammatory programmed cell death, has been implicated in type 2 diabetes mellitus (T2DM) and its complications. Nonetheless, it remains elusive exactly which pyroptosis molecule exerts an essential role in T2DM, and this study aims to solve such issue.Transcriptional profiling datasets of T2DM, i.e., GSE20966, GSE95849, and GSE26168, were acquired. Four machine learning models, namely, random forest, support vector machine, extreme gradient boosting, and generalized linear modeling, were built based on pyroptosis genes. A nomogram of key pyroptosis genes was also generated, and the clinical value was appraised via calibration curves and decision curve analysis. Immune infiltration was inferred utilizing CIBERSORT. Drug–druggable target relationships were acquired from the Drug Gene Interaction Database. Through WGCNA, key pyroptosis-relevant genes were selected.Most pyroptosis genes exhibited upregulation in T2DM relative to controls, indicating the activity of pyroptosis in T2DM. The SVM model composed of BAK1, CHMP2B, NLRP6, PLCG1, and TIRAP exhibited the best performance in T2DM diagnosis, with AUC = 1. The nomogram can predict the risk of T2DM for clinical practice. NK cells resting exhibited a lower abundance in T2DM versus normal specimens, with a higher abundance of neutrophils. NLRP6 was positively linked with neutrophils. Drugs (keracyanin, 9,10-phenanthrenequinone, diclofenac, phosphomethylphosphonic acid adenosyl ester, acetaminophen, cefixime, aspirin, ustekinumab) potentially targeted the key pyroptosis genes. Additionally, CHMP2B-relevant genes were determined.Altogether, this work proposes the key pyroptosis genes in T2DM, which might become possible molecules for the management and treatment of T2DM and its complications.

Application of multiple machine learning approaches to determine key pyroptosis molecules in type 2 diabetes mellitus

Schisandra chinensis, as a Chinese functional food, is rich in unsaturated fatty acids, minerals, vitamins, and proteins. Hence, this study was intended to elucidate the effects and biological mechanism of Schisandrin A from Schisandra chinensis in DN. C57BL/6 mice were fed with a high-fat diet and then injected with streptozotocin (STZ). Human renal glomerular endothelial cells were stimulated with 20 mmol/L d-glucose for DN model. Schisandrin A presented acute kidney injury in mice of DN. Schisandrin A reduced oxidative stress and inflammation in model of DN. Schisandrin A reduced high glucose-induced ferroptosis and reactive oxygen species (ROS-)-mediated pyroptosis by mitochondrial damage in model of DN. Schisandrin A directly targeted AdipoR1 protein and reduced LPS+ATP-induced AdipoR1 ubiquitination in vitro model. Schisandrin A activated AdipoR1/AMPK signaling pathway and suppressed TXNIP/NLRP3 signaling pathway in vivo and in vitro model of DN. Conclusively, our study revealed that Schisandrin A from Schisandra chinensis attenuates ferroptosis and NLRP3 inflammasome-mediated pyroptosis in DN by AdipoR1/AMPK-ROS/mitochondrial damage. Schisandrin A is a possible therapeutic option for DN or other diabetes.

/pdf/schisandrin-a-from-schisandra-chinensis-attenuates-1bx77wlo.pdf

Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination

Background: Propylthiouracil (PTU) treats hyperthyroidism and thyroid crisis in all age groups. A variety of serious adverse effects can occur during clinical use and require attention to its pharmacokinetic and pharmacodynamic characteristics in various populations. Objective: To provide information for individualized dosing and clinical evaluation of PTU in the clinical setting by developing a physiologically based pharmacokinetic (PBPK) model, predicting ADME characteristics, and extrapolating to elderly and pediatric populations. Methods: Relevant databases and literature were retrieved to collect PTU’s pharmacochemical properties and ADME parameters, etc. A PBPK model for adults was developed using PK-Sim® software to predict tissue distribution and extrapolated to elderly and pediatric populations. The mean fold error (MFE) method was used to compare the differences between predicted and observed values to assess the accuracy of the PBPK model. The model was validated using PTU pharmacokinetic data in healthy adult populations. Result: The MFE ratios of predicted to observed values of AUC0-t, Cmax, and Tmax were mainly within 0.5 and 2. PTU concentrations in various tissues are lower than venous plasma concentrations. Compared to healthy adults, the pediatric population requires quantitative adjustment to the appropriate dose to achieve the same plasma exposure levels, while the elderly do not require dose adjustments. Conclusion: The PBPK model of PTU was successfully developed, externally validated, and applied to tissue distribution prediction and special population extrapolation, which provides a reference for clinical individualized drug administration and evaluation.

/pdf/predictive-performance-and-verification-of-physiologically-2bxx052i.pdf

Predictive performance and verification of physiologically based pharmacokinetic model of propylthiouracil

Chenglin Liu1,2*, Chao Dun1,2, Yuanyuan Yang3, Xiaohu Wang3, Chao Tong1,2, Zhihui Zhang1,2, Mengxue Chen and Yu Li1,2 1College of Geoscience, China University of Petroleum, Beijing, 102249, China 2State Key Laboratory of Petroleum Resource and Prospecting, China University of Petroleum, Beijing, 102249, China 3Institute of Geomechanics, Chinese Academy of Geological Sciences, Beijing, 100081, China

https://madridge.org/international-journal-of-petrochemistry/ijpr-1000109.pdf

Xiaohu Wang

Papers

Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination

Anthraxolite Evolution and Vanadium Enrichment Mechanism in the Tanjianshan Group, Upper Ordovician in the Northern Qaidam Basin

Predictive performance and verification of physiologically based pharmacokinetic model of propylthiouracil

Paragenesis mechanism of anthraxolite and vanadium: A case study of the Tanjianshan Group in the Northern Margin of the Qaidam Basin

Development and Validation of Physiologically Based Pharmacokinetic Model of Levetiracetam to Predict Exposure and Dose Optimization in Pediatrics.