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Streptococcus oralis (S. oralis) has been recognized as a fatal pathogen to cause multiorgan failure by contributing to the formation of microthrombus. Coagulation and fibrinolysis systems have been found under the control of circadian clock genes. This study aimed to explore the correlation between BMAL1 and coagulation factor biosynthesis in S. oralis infection. Mice were administered S. oralis to induce sepsis, and HepG2 cells were also infected by S. oralis. The expression of BMAL1 of hepatocytes was downregulated in the S. oralis infection group, leading to the downregulation of coagulation factor VII (FVII) and the upregulation of the coagulation factor XII (FXII) in vitro and in vivo. Furthermore, we confirmed that the deficiency of BAML1 contributed to the elevation of FVII and the decline in FXII by constructing BMAL1-deficiency (Bmal1−/−) mice. The current result showed that BMAL1 regulates FVII directly. Thus, a novel insight into the coagulation abnormality in S. oralis infection was gained that may optimize the treatment of sepsis by rescuing the expression of BMAL1 in the liver.

Rationale: Atherosclerotic cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerotic cardiovascular diseases are considered as chronic inflammation processes. In addition to risk factors associated with the cardiovascular system itself, pathogenic bacteria such as the periodontitis-associated Porphyromonas gingivalis ( P gingivalis ) are also closely correlated with the development of atherosclerosis, but the underlying mechanisms are still elusive. Objective: To elucidate the mechanisms of P gingivalis -accelerated atherosclerosis and explore novel therapeutic strategies of atherosclerotic cardiovascular diseases. Methods and Results: Bmal1 −/− (brain and muscle Arnt-like protein 1) mice, ApoE −/− mice, Bmal1 −/− ApoE −/− mice, conditional endothelial cell Bmal1 knockout mice ( Bmal1 fl/fl ; Tek -Cre mice), and the corresponding jet-legged mouse model were used. P gingivalis accelerates atherosclerosis progression by triggering arterial oxidative stress and inflammatory responses in ApoE −/− mice, accompanied by the perturbed circadian clock. Circadian clock disruption boosts P gingivalis -induced atherosclerosis progression. The mechanistic dissection shows that P gingivalis infection activates the TLRs-NF-κB signaling axis, which subsequently recruits DNMT-1 to methylate the BMAL1 promoter and thus suppresses BMAL1 transcription. The downregulation of BMAL1 releases CLOCK, which phosphorylates p65 and further enhances NF-κB signaling, elevating oxidative stress and inflammatory response in human aortic endothelial cells. Besides, the mouse model exhibits that joint administration of metronidazole and melatonin serves as an effective strategy for treating atherosclerotic cardiovascular diseases. Conclusions: P gingivalis accelerates atherosclerosis via the NF-κB-BMAL1-NF-κB signaling loop. Melatonin and metronidazole are promising auxiliary medications toward atherosclerotic cardiovascular diseases.

Strategies to promote bone regeneration have been always the focus of investigations since the skeleton plays important roles like mechanical support, organ protection, and mineral homeostasis maintenance in the normal physiological activities of the human body. Magnetic fields have shown to be highly influential in the regeneration process, arousing tremendous interest in utilizing magnetic materials to enhance osteogenesis. In this work, we attempt a more comprehensive and detailed review of magnetic materials in promoting bone regeneration by including not only the mechanisms of bone regeneration, the history and basic concepts of magnetism, but also the types of magnetic materials as well as their influence parameters, designs and fabrication techniques with a focus on their usage in the field of bone regeneration like 3D printed scaffolds and implants. In addition, we provide some possible ideas on the synergistic action between magnetic and other materials on bone tissue. Finally, we propose the development trend of magnetic materials in the field of bone regeneration in the future. There is a huge demand for a more effective and less traumatic way to accelerate bone regeneration of the patients with diseases like fractures, tumors and osteoporosis that cause severe pains, bone loss, limb deformations, and restrictions of mobility. Magnetic materials have substantial potential to be manufactured into novel clinical applications with the ability to increase the bone regeneration efficiency.

Intoxicated driving causes 10,000 deaths annually. Smartphone sensing of user gait (walk) to identify intoxicated users in order to prevent drunk driving, have recently emerged. Such systems gather motion sensor (accelerometer and gyroscope) data from the users' smartphone as they walk and classify them using machine or deep learning. Standard Field Sobriety Tests (SFSTs) involve various types of walks designed to cause an intoxicated person to lose their balance. However, SFSTs were designed to make intoxication apparent to a trained law enforcement officer who manually proctors them. No prior work has explored which types of walk yields the most accurate results when assessed autonomously by a smartphone intoxicated gait assessment system. In this paper, we compare how accurately Long Short Term Memory (LSTM), Convolution Neural Network (CNN), Random Forest, Gradient Boosted Machines (GBM) and neural network classifiers are able to detect intoxication levels of drunk subjects who performed normal, walk-and-turn and standing on one foot SFST walks. We also compared the accuracy of intoxication detection on the ascending (increasing intoxication) vs descending (decreasing intoxication) limbs of drinking sessions (bi-phasic). We found smartphone intoxication sensing more accurate on the descending limb of the drinking episode and that intoxication detection on the normal walks of subjects were just as accurate as the SFSTs.