Anti-Inflammatory Dipeptide, a Metabolite from Ambioba Secretion, Protects Cerebral Ischemia Injury by Blocking Apoptosis Via p-JNK/Bax Pathway

MQ (l-methionyl-l-glutamic acid), anti-inflammatory dipeptide, is one of the metabolites of monocyte locomotion inhibitory factor, a thermostable pentapeptide secreted by Entamoeba histolytica. Monocyte locomotion inhibitory factor injection has been approved as an investigational drug for the potential neural protection in acute ischemic stroke. This study further investigated the neuroprotective effect of MQ in ischemic brain damage. Ischemia-reperfusion injury of the brain was induced in the rat model by middle cerebral artery occlusion. 2,3,5-triphenyltetrazolium chloride staining assay was used to measure cerebral infarction areas in rats. Laser Doppler measurement instrument was used to detect blood flow changes in the rat model. Nissl staining and NeuN staining were utilized to observe the numbers and structures of neuron cells, and the pathological changes in the brain tissues were examined by hematoxylin–eosin staining. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining was used to assess cell apoptosis. The changes in oxidative stress indexes, superoxide dismutase and malondialdehyde (MDA), were measured in serum. Methyl thiazolyl tetrazolium was used to measure the survival rates of PC12 cells. Flow cytometry assessed the apoptosis rates and the levels of reactive oxygen species. Real-time PCR was used to evaluate the mRNA expression levels, and Western blotting was used to analyze the changes in protein levels of p-JNK, Bax, cleaved Caspase3. We revealed that MQ improved neurobehavior, decreased cerebral infarction areas, altered blood flow volume, and the morphology of the cortex and hippocampus. On the other hand, it decreased the apoptosis of cortical neurons and the levels of MDA, and increased the levels of superoxide dismutase. In vitro studies demonstrated that MQ enhanced the cell survival rates and decreased the levels of reactive oxygen species. Compared to the oxygen-glucose deprivation/reperfusion group, the protein and mRNA expressions of p-JNK, Bax, cleaved Caspase3 was decreased significantly. These findings suggested that MQ exerts a neuroprotective effect in cerebral ischemia by blocking apoptosis via the p-JNK/Bax pathway

PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma.

For clear cell renal cell carcinoma (ccRCC), lipid deposition plays important roles in the development, metastasis, and drug resistance. However, the molecular mechanisms underlying lipid deposition in ccRCC remain largely unknown. By conducting an unbiased CRISPR-Cas9 screening, we identified the epigenetic regulator plant homeodomain finger protein 8 (PHF8) as an important regulator in ccRCC lipid deposition. Moreover, PHF8 is regulated by von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) axis and essential for VHL deficiency-induced lipid deposition. PHF8 transcriptionally up-regulates glutamate-ammonia ligase (GLUL), which promotes the lipid deposition and ccRCC progression. Mechanistically, by forming a complex with c-MYC, PHF8 up-regulates TEA domain transcription factor 1 (TEAD1) in a histone demethylation-dependent manner. Subsequently, TEAD1 up-regulates GLUL transcriptionally. Pharmacological inhibition of GLUL by l-methionine sulfoximine not only repressed ccRCC lipid deposition and tumor growth but also enhanced the anticancer effects of everolimus. Thus, the PHF8-GLUL axis represents a potential therapeutic target for ccRCC treatment

Spatiotemporal evolution and driving forces of ecosystem service value and ecological risk in the Ulan Buh Desert

A clear understanding of the spatiotemporal evolution and driving factors of ecosystem service value (ESV) and the landscape ecological risk index (ERI) can effectively link human well-being and ecosystem security, which is essential for sustainable ecosystem management. Based on multitemporal land use data (1990, 2000, 2010, and 2018), the spatiotemporal evolution of ESV and the ERI in the Ulan Buh Desert was evaluated. The driving forces of ESV and the ERI were quantitatively evaluated by the Geodetector model. The results show that 1) from 1990 to 2018, total ESV in the Ulan Buh Desert increased from 7.00×108 yuan to 11.09×108 yuan. Low-ESV areas accounted for approximately 72.28% of the study area. High-ESV and moderate-high-ESV areas were mainly distributed along the Yellow River and the northeastern region. 2) During the study period, the ecological risk of the Ulan Buh Desert generally decreased; only the ecological risk of the northeastern region improved significantly, and high-risk areas were mainly distributed across sand dunes located in the middle of the desert. 3) There was a negative correlation between ESV and the ERI in the study area, and the main relationship was low value-high risk. 4) Driving force analysis results show that natural and human impact factors jointly affected the spatiotemporal differentiation of ESV and the ERI in the Ulan Buh Desert. Among the influencing factors, the interaction between the distance to a highway and annual precipitation had the strongest impact. The implementation of relevant policies in the study area should be guided by ESV and the ERI, and the protection and restoration of various ecosystems in the study area must be strengthened

A Systematic Way to Extend the Debye–Hückel Theory beyond Dilute Electrolyte Solutions

An extended Debye–Hückel theory with fourth order gradient term is developed for electrolyte solutions; namely, the electric potential φ(r) of the bulk electrolyte solution can be described by ∇2φ(r) = κ2φ(r) + LQ2∇4φ(r), where the parameters κ and LQ are chosen to reproduce the first two roots of the dielectric response function of the bulk solution. Three boundary conditions for solving the electric potential problem are proposed based upon the continuity conditions of involving functions at the dielectric boundary, with which a boundary element method for the electric potential of a solute with a general geometrical shape and charge distribution is derived. Solutions for the electric potential of a spherical ion and a diatomic molecule are found and used to calculate their electrostatic solvation energies. The validity of the theory is successfully demonstrated when applied to binary as well as multicomponent primitive models of electrolyte solutions.This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in The Journal of Physical Chemistry A, copyright © American Chemical Society after peer review. To access the final edited and published work see DOI: 10.1021/acs.jpca.0c10226. Posted with permission.</p

A Systematic Way to Extend the Debye–Hückel Theory beyond Dilute Electrolyte Solutions

An extended Debye–Hückel theory with fourth order gradient term is developed for electrolyte solutions; namely, the electric potential φ(r) of the bulk electrolyte solution can be described by ∇2φ(r) = κ2φ(r) + LQ2∇4φ(r), where the parameters κ and LQ are chosen to reproduce the first two roots of the dielectric response function of the bulk solution. Three boundary conditions for solving the electric potential problem are proposed based upon the continuity conditions of involving functions at the dielectric boundary, with which a boundary element method for the electric potential of a solute with a general geometrical shape and charge distribution is derived. Solutions for the electric potential of a spherical ion and a diatomic molecule are found and used to calculate their electrostatic solvation energies. The validity of the theory is successfully demonstrated when applied to binary as well as multicomponent primitive models of electrolyte solutions.</p

A Molecular Debye-Hückel Theory and Its Applications to Electrolyte Solutions

In this report, a molecular Debye-Hückel theory for ionic fluids is developed. Starting from the macroscopic Maxwell equations for bulk systems, the dispersion relation leads to a generalized Debye-Hückel theory which is related to the dressed ion theory in the static case. Due to the multi-pole structure of dielectric function of ionic fluids, the electric potential around a single ion has a multi-Yukawa form. Given the dielectric function, the multi-Yukawa potential can be determined from our molecular Debye-Hückel theory, hence, the electrostatic contributions to thermodynamic properties of ionic fluids can be obtained. Applications to binary as well as multi-component primitive models of electrolyte solutions demonstrated the accuracy of our approach. More importantly, for electrolyte solution models with soft short-ranged interactions, it is shown that the traditional perturbation theory can be extended to ionic fluids successfully just as the perturbation theory has been successfully used for short-ranged systems.The following article appeared in Journal of Chemical Physics 135 (2011): 104104, and may be found at doi:10.1063/1.3632052.</p