Therapeutic potentials of allicin in cardiovascular disease: advances and future directions.

Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin's cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin's clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.

High-intensity interval training ameliorates chronic unpredictable mild stress-induced depressive behaviors via HDAC2-BDNF signaling in the ventral hippocampus.

Major depressive disorder (MDD) is a devastating psychiatric disease, and current therapies could not well meet the demand for MDD treatment. Exercise benefits mental illness, and notably, exercise has been recommended as an alternative option for MDD treatment in some countries. However, the paradigm and intensity of exercise for MDD treatment has yet to be determined. High-intensity interval training (HIIT) is a potent and time-efficient type of exercise training and has gained popularity in recent years. In this study, we exposed the mice to chronic unpredictable mild stress (CUMS) and found HIIT exerted substantial antidepressant effect. Moreover, HIIT further enhanced the antidepressant effect of fluoxetine, a classic antidepressant in the clinic, confirming the antidepressant role of HIIT. HIIT significantly reversed the CUMS-induced upregulations in HDAC2 mRNA and protein level in the ventral hippocampus. We also found HIIT rescued the CUMS-induced downregulation in the expression of brain-derived neurotrophic factor (BDNF) and HDAC2 overexpression counteracted the HIIT-induced increase in BDNF level. More importantly, both virus-mediated HDAC2 overexpression and microinfusion of TrkB-Fc, a BDNF scavenger, in the ventral hippocampus abolished the antidepressant effect of HIIT. Together, our results strongly demonstrate that HIIT attenuates depressive behaviors, probably via HDAC2-BDNF signaling pathway and reveal that HIIT may serve as an alternative option for MDD treatment.

Numerical investigation of the rider's head injury in typical single-electric self-balancing scooter accident scenarios.

As the use of electric self-balancing scooters (ESSs) increases, so does the number of related traffic accidents. Because of the special control method, mechanical structure and driving posture, ESSs are prone to various single-vehicle accidents, such as collisions with fixed obstacles and falls due to mechanical failures. In various ESS accident scenarios, the rider's head injury is the most frequent injury type. In this study, several typical single-ESS accident scenarios are reconstructed via computational methods, and the risk of riders' head/brain injury is assessed in depth using various injury criteria. Results showed that two types of ESSs (solo- and two-wheeler) do not have clear differences in head kinematics and head injury risks; the head kinematics (or falling posture) and ESS accident scenario exhibit a distinct effect on the head injury responses; half of the analysed ESS riders have a 50% probability of skull fracture, a few riders have a 50% risk of abbreviated injury scale (AIS) 4+ brain injury, and none has a diffuse axonal injury; the ESS speed plays an important role in producing the head/brain injury in ESS riders, and generally, higher ESS speed generates higher level of predicted head injury parameters. These findings will provide theoretical support for preventing head injury among ESS riders and data support for developing and legislating ESSs.

Should anthropometric differences between the commonly used pedestrian computational biomechanics models and Chinese population be taken into account when predicting pedestrian head kinematics and injury in vehicle collisions in China?

Computational biomechanics models play a key role in predicting/evaluating pedestrian head kinematics and injury risk in car-to-pedestrian collisions. The human multibody models most commonly used in car-to-pedestrian collision reconstruction, such as pedestrian model by The Netherlands Organisation for Applied Scientific Research TNO, are built using the anthropometry of Western European population as defined in TNO (2013) human multibody model database. In this study, we investigate the effects of the anthropometric differences between the Western European and Chinese populations on the pedestrian head kinematics and injury responses predicted using multibody models. The comparison was conducted through car-to-pedestrian collision simulations using pedestrian multibody models representing anthropometric characteristics of Western European and Chinese populations, three typical vehicle shapes (sedan, SUV and minivan), five initial vehicle impact speeds (30, 35, 40, 45, 50 km/h), and six pedestrian walking postures. The results indicate that the change of pedestrian model anthropometry (from Western European to Chinese) exerts appreciable effects on both the predicted initial boundary conditions of the head-to-windscreen impact (in particular the head-to-windscreen impact angle) and the head injury indices in the impact with the road surface (secondary impact).

Atorvastatin ameliorates depressive behaviors via regulation of α7nAChR expression by PI3K/Akt-BDNF pathway in mice.

Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4ß2 nicotinic acetylcholine receptor (α4ß2nAchR) expression in vHPC, nor the α7nAChR and α4ß2nAchR expression in dorsal hippocampus (dHPC). By using MLA, a selective α7nAChR antagonist, we investigated the role of α7nAChR in AV treatment. Behavior tests demonstrated that MLA abolished the antidepressant effect of AV. Besides, our data showed that AV treatment increased Akt phosphorylation, brain-derived neurotrophic factor (BDNF), synaptic related protein synapsin and spinophilin expression. The phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 reversed AV-induced increase of BDNF expression, newborn neurons and antidepressant behavior effects. Our study suggests that AV plays an antidepressant role by regulating synaptic plasticity of vHPC through PI3K/Akt-BDNF signaling pathway, which may be a good choice for depression treatment.

Confined Crystallization and Melting Behaviors of 3-Pentadecylphenol in Anodic Alumina Oxide Nanopores.

To explore the effects of end groups on the confined crystallization of an alkyl chain, 3-pentadecylphenol (PDP) was infiltrated into the anodic aluminum oxide template (AAO) to investigate the melting and crystallization behaviors of PDP in a nanoconfined environment. Wide-angle X-ray diffraction (WAXD) found that the solid-solid phase transition of PDP occurred under confined conditions, and the absence of the (00L) reflections indicated that the stacking of the end groups of the alkyl chain layered structure was seriously disturbed. Thermal analysis (TG) showed that the thermal stability of the confined samples decreased due to the confinement effect, and the introduction of end groups made the confinement effect more obvious. Differential scanning calorimeter (DSC) results well reflected the space-time equivalence in the PDP crystallization processes, i.e., the solid-solid phase transition can be achieved by reducing the cooling rate or confining PDP in the nanometer space. Compared with C15, the introduction of the end groups with a phenol ring led to the disappearance of the solid-solid phase transition of an alkyl chain at high cooling rates. In the confined environment, the introduction of the end groups with a phenol ring caused the melting double peaks of the alkyl chain to become a single melting peak, and it also caused the disappearance of the surface freezing monolayer for alkyl chains. Through the analysis of crystallinity, it was found that AAO-PDP was more sensitive to AAO pore size changes than AAO-C15, the X c of AAO-PDP had a good linear relationship with the pore size d, but the X c of the AAO-C15 had a nonlinear relationship with the pore size d. Attenuated total reflection (ATR)-IR proved that in the confined environment, the order of the alkyl chain decreased and the degree of chain distortion increased.