Ancient genomes illuminate the demographic history of Shandong over the past two millennia.

Shandong province, located in the Lower Yellow River, is one of the birthplaces of ancient Chinese civilization. However, the comprehensive genetic histories of this region have remained largely unknown until now due to a lack of ancient human genomes. Here, we present 21 ancient genomes from Shandong dating from the Warring States period to the Jin-Yuan Dynasties. Unlike the early Neolithic samples from Shandong, the historical samples are most closely related to post-Late Neolithic populations of the Middle Yellow River Basin, suggesting a population turnover in Shandong from the Neolithic Age to the Historical era. In addition, we detect a close genetic affinity between the historical samples in Shandong and present-day Han Chinese, showing long-term genetic stability in Han Chinese at least since the Warring States period.

No causal link between herpes zoster and ischemic stroke: evidence from Mendelian randomization study.

OBJECTIVE: The association between herpes zoster (HZ) and stroke has been the subject of much previous research. Nevertheless, the connection remains ambiguous. A two-sample Mendelian randomisation study was conducted to explore the potential causal link between HZ and ischaemic stroke, including its subtypes. METHODS: For our MR analysis, we identified genetic instrumental variables related to both HZ and stroke by screening two prominent publicly accessible genome-wide association study databases. The primary approach involved using the inverse variance weighting method. To supplement this, we also employed methods such as MR-Egger regression, the weighted median approach, simple and weighted models. Lastly, to ascertain the stability and reliability of the results, we conducted tests for heterogeneity detection, horizontal pleiotropy assessment, and a leave-one-out analysis. RESULTS: The genetically predicted HZ did not indicate an association with stroke risk ([OR] 1.041; 95% [CI] 0.958-1.131;p = 0.336). This lack of association also held true for different subtypes of stroke: ischaemic stroke (OR = 1.047, 95% CI = 0.955-1.148, p = 0.323), large vessel stroke (OR = 1.13, 95% CI = 0.90-1.41, p = 0.272), cardioembolic stroke (OR = 1.020, 95% CI = 0.859-1.211, p = 0.816), small vessel stroke (OR = 1.14, 95% CI = 0.93-1.40, p = 0.195), and lacunar stroke (OR = 1.195, 95% CI = 0.967-1.476, p = 0.097). CONCLUSION: This MR study showed that not uncover a causal link between herpes zoster and ischaemic stroke. Additional research will be necessary in the future to shed light on the fundamental mechanisms involved.

Effects of Qishen Dihuang Granules on Intestinal Microbiota in Experimental Autoimmune Myasthenia Gravis Model Rats.

Objective: Effects of Qishen Dihuang (QSDH) granules on intestinal flora of an experimental autoimmune myasthenia gravis (EAMG) model rat were investigated (CNBI:PRJNA910532). Methods: Thirty-six female Lewis rats were assigned to Control, EAMG, QSDH-low-dose, QSDH-medium-dose, QSDH-high-dose, and Prednisone groups using the random number table method (6 rats/group). A rat EAMG model was established by injecting Rα97-116 peptide antigen. Each day for 30 days, gavages were administered to rats in the Chinese medicine group (QSDH granules in different concentrations), Prednisone group (prednisone), and Control and Model groups (0.5% CMC). After 30-day gavages, rat fecal samples were collected and the microbial community composition and diversity differences between intestinal microbiota of EAMG and QSDH granule-treated groups were analyzed using 16S amplicon sequencing to explore the effect underlying QSDH granules alleviation of EAMG. Results: The clinical symptoms of rats in each treatment group improved significantly after the intervention treatment with QSDH granules. Comparison of the relative abundance of microorganisms in the gut flora of different groups with that of the EAMG group rats revealed: significantly lower phylum-level Bacteroidetes abundance and significantly greater Actinobacteria abundance in the QSDH-high-dose group and a significantly greater Firmicutes/Bacteroidetes ratio in the QSDH-medium-dose group; significantly increased family-level QSDH-high-dose group abundances of Lachnospiraceae and Trichospiraceae (Firmicutes), significantly increased QSDH-medium-dose group Lactobacillaceae abundance, and significantly increased QSDH-low-dose group Bacteroidaceae abundance; genus-level, QSDH-high-dose group Prevotella and Coprococcus abundances were significantly increased and Turicibacter and Lactobacillus abundances were significantly decreased, while QSDH-medium-dose group Akkermansia and Lactobacillus abundances were significantly increased. Greater overall community richness, diversity, and genetic diversity were observed in QSDH granules-treated groups, but differences were insignificant (P > .05). The most significant inter-group genus-level community marker differences involved Prevotella, Ruminococcus, Coprococcus, and Turicibacter. Conclusion: QSDH granules may regulate EAMG rat intestinal flora by decreasing relative abundances of Turicibacter and Clostridium and increasing relative abundances of Bifidobacterium, Lachnospiraceae, and Prevotella.

Exploring the Potential Mechanism of Qi-Shen-Di-Huang Drug Formulary for Myasthenia Gravis (MG) based on UHPLC-QE-MS Network Pharmacology and Molecular Docking Techniques.

Myasthenia gravis (MG) is a rare and refractory autoimmune disease, and Qi Shen Di Huang (QSDH) drug formulary is an in-hospital herbal decoction with proven clinical efficacy in treating MG. Currently, most of the research on the QSDH drug formulary has concentrated on its clinical efficacy, and there is a lack of systematic study on the material basis. The active compounds and their mechanism of action have not been entirely determined. Therefore, this study sought to identify the active compounds in the QSDH drug formulary and analyze the key targets and potential mechanisms. We used ultra-performance liquid chromatography Q Exactive-mass spectrometry (UHPLC-QE-MS) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database to identify and screen 85 active ingredients corresponding to 59 potential targets (17 herbs) associated with myasthenia gravis, and further identified AKT1 as the primary core target and the PI3K/AKT signaling pathway as the most substantial enriched pathway. Molecular docking and UPLC-MS analysis identified quercetin, luteolin, wogonin, kaempferol, laccasein, and epigallocatechin gallate are the core compounds of the QSDH drug formulary. In vivo rat studies showed that the QSDH drug formulary reduced Lennon's clinical score and decreased acetylcholine receptor antibody levels in peripheral blood rats with experimental autoimmune myasthenia gravis. In addition, the QSDH drug formulary downregulated P-PI3K/PI3K and P-Akt/Akt protein expression. Collectively, these findings describe the role and potential mechanism of the QSDH drug formulary in the treatment of MG, which exerts potential value by acting on AKT targets and regulating the PI3K/AKT signaling pathway and providing a theoretical reference for QSDH drug formulary application in the clinical treatment of MG.

Lower-body posture estimation with a wireless smart insole.

Typical optical marker and camera based systems for motion capture suffer from several limitations. They are restricted to indoor environments, have difficulties tracking multiple people simultaneously and require expensive camera setups. In this work, we present a new method for lower-body posture estimation with a wireless smart insole using end-to-end training of a deep neural network. Our model is able to predict the movement of the entire lower body (including the hip, knee, ankle and toe) accurately in a wide range of activities. Inference only takes 1.62ms and hence can be used in real-time. The proposed method can potentially provide a very efficient and portable solution for applications like sports analysis, rehabilitation and virtual reality.

FreeWalker: a smart insole for longitudinal gait analysis.

Gait analysis is an important diagnostic measure to investigate the pattern of walking. Traditional gait analysis is generally carried out in a gait lab, with equipped force and body tracking sensors, which needs a trained medical professional to interpret the results. This procedure is tedious, expensive, and unreliable and makes it difficult to track the progress across multiple visits. In this paper, we present a smart insole called FreeWalker, which provides quantitative gait analysis outside the confinement of traditional lab, at low- cost. The insole consists of eight pressure sensors and two motion tracking sensors, i.e. 3-axis accelerometer and 3-axis gyroscope. This enables measurement of under-foot pressure distribution and motion sequences in real-time. The insole is enabled with onboard SD card as well as wireless data transmission, which help in continuous gait-cycle analysis. The data is then sent to a gateway, for analysis and interpretation of data, using a user interface where gait features are graphically displayed. We also present validation result of a subject's left foot, who was asked to perform a specific task. Experiment results show that we could achieve a data-sampling rate of over 1 KHz, transmitting data up to a distance of 20 meter and maintain a battery life of around 24 hours. Taking advantage of these features, FreeWalker can be used in various applications, like medical diagnosis, rehabilitation, sports and entertainment.

A 1024-channel 6 mW/mm2 optical stimulator for in-vitro neuroscience experiments.

Recent optical stimulation technologies allow improved selectivity and have been widely used in neuroscience research. This paper presents an optical stimulator based on high power LEDs. It has 1024 channels and can produce flexible stimulation patterns in each frame, refreshed at above 20 Hz. To increase the light intensity, each LED has an optical package that directs the light into a small angle. To ensure the light of each LED can reach the lens, the LEDs have been specially placed and oriented to the lens. With these efforts, the achieved power efficiency (defined as the mount of LED light power passing through the lens divided by the LED total power consumption) is 5 × 10(-5). In our current prototype, an individual LED unit can source 60 mW electrical power, where the induced irradiance on neural tissues is 6 mW/mm(2) integrating from 460 nm to 480 nm. The light spot is tunable in size from 18 µm to 40 µm with an extra 5-10 µm separation for isolating two adjacent spots. Through both bench-top measurement and finite element simulation, we found the cross channel interference is below 10%. A customized software interface has been developed to control and program the stimulator operation.