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[Display omitted] Aortic Aneurysm and Dissection (AAD) are severe cardiovascular conditions with potentially lethal consequences such as aortic rupture. Existing studies suggest that liraglutide, a long-acting glucagon-like peptide receptor (GLP-1R) agonist, offers protective benefits across various cardiovascular diseases. However, the efficacy of liraglutide in mitigating AAD development is yet to be definitively elucidated. Ang II (Angiotension II) infusion of APOE-/- mouse model with intraperitoneal injection of liraglutide (200 μg/kg) to study the role of GLP-1R in AAD formation. Bone Marrow Derived Macrophages (BMDM) and Raw264.7 were incubated with LPS, liraglutide, exendin 9–39 or LY294002 alone or in combination. SMC phenotype switching was examined in a macrophage and vascular smooth muscle cell (VSMC) co-culture system. An array of analytical methods, including Western Blot, Immunofluorescence Staining, Enzyme-Linked Immunosorbent Assay, Real-Time Quantitative Polymerase Chain Reaction, RNA-seq, and so on were employed. Our investigation revealed a significant increase in M1 macrophage polarization and GLP-1R expression in aortas of AD patients and Ang II-induced AAD APOE-/- mice. Administering liraglutide in APOE-/- mice notably reduced Ang II-induced AAD incidence and mortality. It was found that liraglutide inhibits M1 macrophage polarization primarily via GLP-1R activation, and subsequently modulates vascular smooth muscle cell phenotypic switching was the primary mechanism. RNA-Seq and subsequent KEGG enrichment analysis identified CXCL3, regulated by the PI3K/AKT signaling pathway, as a key element in liraglutide's modulation of M1 macrophage polarization. Our study found liraglutide exhibits protective effects against AAD by modulating M1 macrophage polarization, suppressing CXCL3 expression through the PI3K/AKT signaling pathway. This makes it a promising therapeutic target for AAD, offering a new avenue in AAD management. [ABSTRACT FROM AUTHOR]

Molecular biology research often requires extraction of DNA fragments from agarose gels. In the past decades, there have been many methods developed for this purpose. Currently most researchers, especially novices, use commercial kits for this extraction, although these kits cost money and the procedures involved are not necessarily easier than some erstwhile methods. We herein reintroduce and reassess several simple and cost-free older methods. One method involves excising a slice of the gel containing the DNA fragment, followed by a thaw-and-freeze procedure to release the DNA from the gel slice into the gel-making buffer. The second method involves a dialysis tubing and requires electroelution of the DNA from the gel slice in the tubing. The third one is to centrifuge the gel slice to release the DNA. The fourth method requires electro-transfer of the DNA from the gel into a filter paper, while the fifth one includes either allowing the DNA in the slice to be dissolved into a buffer or dissolving the DNA-containing gel slice, followed by DNA precipitation with ethanol or isopropanol. The strengths and weaknesses of these methods are discussed to assist researchers in making their choice. We also point out that some of the end uses of the DNA fragment in the agarose gel may not actually require extraction of the DNA. For instance, a tiny DNA-containing gel block or filter paper can be directly used as the template in a nested or semi-nested polymerase chain reaction to preliminarily determine the identity of the DNA fragment. [ABSTRACT FROM AUTHOR]

Delirium is the most common neurological complication after cardiac surgery with adverse impacts on surgical outcomes. Advanced age is an independent risk factor for delirium occurrence but its underlying mechanisms are not fully understood. Although increased A1 astrocytes and abnormal hippocampal networks are involved in neurodegenerative diseases, whether A1 astrocytes and hippocampal network changes are involved in the delirium‐like behavior of aged mice remains unknown. In the present study, a mice model of myocardial ischemia–reperfusion mimicking cardiac surgery and various assessments were used to investigate the different susceptibility of the occurrence of delirium‐like behavior between young and aged mice and the underlying mechanisms. The results showed that surgery significantly increased hippocampal A1 astrocyte activation in aged compared to young mice. The high neuroinflammatory state induced by surgery resulted in glutamate accumulation in the extrasynaptic space, which subsequently decreased the excitability of pyramidal neurons and increased the PV interneurons inhibition through enhancing N‐methyl‐D‐aspartate receptors' tonic currents in the hippocampus. These further induced the abnormal activities of the hippocampal neural networks and consequently contributed to delirium‐like behavior in aged mice. Notably, the intraperitoneal administration of exendin‐4, a glucagon‐like peptide‐1 receptor agonist, downregulated A1 astrocyte activation and alleviated delirium‐like behavior in aged mice, while IL‐1α, TNF‐α, and C1q in combination administered intracerebroventricularly upregulated A1 astrocyte activation and induced delirium‐like behavior in young mice. Therefore, our study suggested that cardiac surgery increased A1 astrocyte activation which subsequently impaired the hippocampal neural networks and triggered delirium development. [ABSTRACT FROM AUTHOR]

Field joint surveys and electro-imaging logging were performed to study the characteristics of fracture development in the Upper Triassic Xujiahe Formation, which is located in the western Sichuan depression. Systematic joints with extensional characteristics have been identified; these likely formed as natural hydraulic fractures. There are four sets of fractures: nearly E–W trending fractures, nearly N–S trending fractures, NW–SE trending fractures, and NE–SW trending fractures; the nearly E–W trending fractures are the most widely developed. We analyze the timing of tectonic events of the Longmenshan orogenic belt and the western Sichuan foreland basin, terminal relationships, and filling characteristics of the joints. Based on this analysis, we proposed that some nearly E–W striking joints (after restored to the horizontal) formed during the Early Cretaceous (~100 Ma), although the Cenozoic (~60 Ma and onward) has been another important period for the formation of joints. This implies that horizontal, N–S wells could be drilled to reopen the sealed E–W striking joints and to gain access to the more permeable E–W striking joints. [ABSTRACT FROM AUTHOR]

China has a long history of earthquake records, and the Longmenshan fault system (LFS) is a famous earthquake zone. We believed that the LFS could be divided into three seismogenic zones (north, central, and south zones) based on the geological structures and the earthquake catalog. We applied the Bayesian probability method using extreme-value distribution of earthquake occurrences to estimate the seismic hazard in the LFS. The seismic moment, slip rate, earthquake recurrence rate, and magnitude were considered as the basic parameters for computing the Bayesian prior estimates of the seismicity. These estimates were then updated in terms of Bayes' theorem and historical estimates of seismicity in the LFS. Generally speaking, the north zone seemingly is quite peaceful compared with the central and south zones. The central zone is the most dangerous; however, the periodicity of earthquake occurrences for M = 8.0 is quite long (1,250 to 5,000 years). The selection of upper bound probable magnitude influences the result, and the upper bound magnitude of the south zone maybe 7.5. We obtained the empirical relationship of magnitude conversion for M and ML, the values of the magnitude of completeness Mc (3.5), and the Gutenberg-Richter b value before applying the Bayesian extreme-value distribution of earthquake occurrences method. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSP) serve as chaperones to maintain the physiological conformation and function of numerous cellular proteins when the ambient temperature is increased. To determine how accurate the general assumption that HSP gene expression is increased in febrile situations is, the RNA levels of the HSF1 (heat shock transcription factor 1) gene and certain HSP genes were determined in three cell lines cultured at 37˚C or 39˚C for three days. At 39˚C, the expression of HSF1, HSPB1, HSP90AA1 and HSP70A1L genes demonstrated complex changes in the ratios of expression levels between different RNA variants of the same gene. Several older versions of the RNAs of certain HSP genes that have been replaced by a newer version in the National Center for Biotechnology Information database were also detected, indicating that the older versions are actually RNA variants of these genes. The present study cloned four new RNA variants of the HSP27-encoding HSPB1 gene, which together encode three short HSP27 peptides. Reanalysis of the proteomics data from our previous studies also demonstrated that proteins from certain HSP genes could be detected simultaneously at multiple positions using SDS-PAGE, suggesting that these genes may engender multiple protein isoforms. These results collectively suggested that, besides increasing their expression, certain HSP and associated genes also use alternative transcription start sites to produce multiple RNA transcripts and use alternative splicing of a transcript to produce multiple mature RNAs, as important mechanisms for responding to an increased ambient temperature in vitro. [ABSTRACT FROM AUTHOR]

Heart failure is a primary cause of global mortality. In the present study, whether larixyl acetate, an inhibitor of transient receptor potential cation channel subfamily C member 6, attenuates pressure overload-induced heart failure in mice was investigated. To test this hypothesis, a transverse aortic constriction (TAC) animal model and an angiotensin II (Ang II)-treated H9c2 cell model were used. Cardiac and cellular structure, function and the expression levels of hypertrophy, endoplasmic reticulum (ER) stress, apoptosis, autophagy and pmTOR/mTOR related mRNAs or proteins were assessed to explore the underlying molecular mechanisms. The results indicated that treatment with TAC or Ang II leads to significant hypertrophy and dysfunction of the heart or H9c2 cells, accompanied by an increase in ER stress, apoptosis and activation of the mTOR signaling pathway, and a decrease in autophagy. The administration of larixyl acetate attenuated these impairments, which can be reversed by inhibiting autophagy through the activation of the mTOR signaling pathway. These findings suggested that larixyl acetate can effectively protect against pressure overload-induced heart failure by enhancing autophagy and limiting ER stress and apoptosis through inhibition of the mTOR pathway. [ABSTRACT FROM AUTHOR]