Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein ( Cirbp ) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp -KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp -KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.

The geotechnical earthquake engineering profession has struggled with the inherent complexity of the multiphase soil response to cyclic loading owing to the progressive nature of the generation of excess pore pressure (EPP) and degradation of soil stiffness and strength. One approach to improve understanding of the cyclic response and correlate the transition from a two-phase saturated soil to a single, fluid-phase liquefied soil is to treat the soil as a non-Newtonian viscous liquid. However, the work to date suggests that the viscous fluid model approach can only be implemented following the onset of sustained soil liquefaction. This paper presents a unified thixotropic fluid model and framework that effectively links the pre-shear soil fabric and its progressive cyclic response to the onset and maintained state of soil liquefaction. The framework treats the soil fabric as a fluid net-type structure proposed for use with thixotropic fluids, and presents the constitutive state and rate equations describing the deconstruction of the liquefiable soil fabric in response to cyclic loading. The unified framework uses physically meaningful soil parameters that can be obtained from common cyclic laboratory tests to seamlessly link the state-dependent and shear-strain-rate-dependent nature of soils to the generation of EPP, the latter of which is shown to increase in significance as EPP accumulates. The proposed thixotropic-induced excess pore pressure model should prove advantageous for use in forward modelling of the stress–strain rate response of liquefiable soil and generation of EPP.

Alzheimer's disease (AD) affects people worldwide and is caused by chronic and progressive damage to the central nervous system. Lycium barbarum (LB), a renowned functional food and medicinal plant in Southeast Asia, may possess protective effects against nerve injury. The present study aimed to investigate the neuroprotective effects of LB water extract in a differentiated (D)PC12 cellular apoptosis model induced by L‑glutamic acid (L‑Glu), and a mouse model of AD, induced by the combination of AlCl3 and D‑galactose. LB markedly increased DPC12 cell survival against L‑Glu induced damage by increasing cell viability, reducing the apoptosis rate and G1 phase arrest, suppressing intracellular reactive oxygen species accumulation, blocking Ca2+ overload and preventing mitochondrial membrane potential depolarization. LB additionally normalized the expression levels of apoptosis regulator Bcl‑2, apoptosis regulator BAX, and cleaved caspase‑3, ‑8 and ‑9 in L‑Glu exposed cells. In the AD mouse model, LB increased the amount of horizontal and vertical movement in the autonomic activity test, improved endurance time in the rotarod test and decreased escape latency time in the Morris water maze test. Additionally, the levels of acetylcholine and choline acetyltransferase were significantly increased in the serum and hypothalamus in the LB‑treated AD mice. These data suggested that LB may exert neuroprotective effects and may aid in preventing neurodegenerative disease.

Hypertension has been recognized as one of the highest risk factors for cardiovascular diseases. Anti-hypertension agent screening and development has been recognized as a pharmaceutical therapy approach for the cardiovascular diseases treatment. Many kinds of traditional Chinese medicines, such as pine needle, have been used for the treatment of hypertension for a long time, but the bioactive ingredients which responsible for their therapeutic effectiveness are remain unclear. Therefore, screening bioactive chemicals in natural sources is still the most straightforward strategy for novel Angiotensin-converting enzyme inhibitor (ACEi)-based anti-hypertension agents discovery. In this study, we demonstrated a bioactivity-guided fractionation strategy for identifying bioactive fractions and chemicals from pine needle based on LC/MS assay as well as elucidating their mechanisms of pharmacological activity. And we found out the compound in pine needle extracts being ACE-inhibitory active is catechin. When ACE activity was assayed in rat tissue membranes, it was observed that catechin demonstrate ACE inhibition in kidney, lung and testes tissue. All these presents catechin in pine needle could be a potential cardiovascular medicine.

LPAR6 is the most recently determined G protein-coupled receptor of lysophosphatidic acid, and hardly any study has demonstrated the performance of LPAR6 in cancers. We sought to clarify the relationship of LPAR6 to prognosis potential and tumor infiltration immune cells in different cancers.