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Abstract Background The gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under‐investigated, and the molecular mechanism remains unclear. Methods To investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi‐ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model. Results The study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non‐sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non‐sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P

BackgroundPeople living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV.MethodsTo test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4+ T-cell counts, HIV reservoir, and other clinical parameters.ResultsCompared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4+ T-cell–associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4+ T-cell level.ConclusionsOur findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV.

Abstract Background Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids that are associated with an increased risk of cardiometabolic diseases (CMD). However, there are still only limited insights into potential direct associations between BCAAs and a wide range of CMD parameters, especially those remaining after correcting for covariates and underlying causal relationships. Methods To shed light on these relationships, we systematically characterized the associations between plasma BCAA concentrations and a large panel of 537 CMD parameters (including atherosclerosis-related parameters, fat distribution, plasma cytokine concentrations and cell counts, circulating concentrations of cardiovascular-related proteins and plasma metabolites) in 1400 individuals from the Dutch population cohort LifeLines DEEP and 294 overweight individuals from the 300OB cohort. After correcting for age, sex, and BMI, we assessed associations between individual BCAAs and CMD parameters. We further assessed the underlying causality using Mendelian randomization. Results A total of 838 significant associations were detected for 409 CMD parameters. BCAAs showed both common and specific associations, with the most specific associations being detected for isoleucine. Further, we found that obesity status substantially affected the strength and direction of associations for valine, which cannot be corrected for using BMI as a covariate. Subsequent univariable Mendelian randomization (UVMR), after removing BMI-associated SNPs, identified seven significant causal relationships from four CMD traits to BCAA levels, mostly for diabetes-related parameters. However, no causal effects of BCAAs on CMD parameters were supported. Conclusions Our cross-sectional association study reports a large number of associations between BCAAs and CMD parameters. Our results highlight some specific associations for isoleucine, as well as obesity-specific effects for valine. MR-based causality analysis suggests that altered BCAA levels can be a consequence of diabetes and alteration in lipid metabolism. We found no MR evidence to support a causal role for BCAAs in CMD. These findings provide evidence to (re)evaluate the clinical importance of individual BCAAs in CMD diagnosis, prevention, and treatment.

Abstract Recent developments have demonstrated that the brake pedal simulator (BPS) is becoming an indispensable apparatus for the break-by-wire systems in future electric vehicles. Its main function is to provide the driver with a comfortable pedal feel to improve braking safety and comfort. This paper presents the development and control of an adjustable BPS, using a disk-type magnetorheological (MR) damper as the passive braking reaction generator to simulate the traditional pedal feel. A detailed description of the mechanical design of the MR damper-based BSP (MRDBBPS) is presented in this paper. Several basic performance experiments on the MRDBBPS prototype are conducted. A return-to-zero (RTZ) algorithm is proposed to avoid hysteresis and improve the repeatability of the pedal force. In addition, an RTZ algorithm-based real-time current-tracking controller (RTZRC) is designed in consideration of the response lag of the coil circuit. Finally, an experimental system is established by integrating the MRDBBPS prototype into a self-developed automotive MR braking test bench (AMRBTB), and several control and braking experiments are performed. This research proposes a RTZRC control algorithm which can significantly increase the tracking accuracy of the brake pedal characteristic curve, particularly at a high pedal velocity. Additionally, the designed MRDBBPS prototype can achieve an effective and favorable control of the AMRBTB with a good repeatability.

Helicobacter pylori infection is a prevalent infectious disease, associated with many gastric diseases, including gastritis, gastric ulcer, and gastric cancer. To reveal the characteristics of the gastric microbiome in patients infected with H. pylori, we performed metagenomic shotgun sequencing of stomach swab samples from 96 patients and then conducted metagenomic association analyses between alterations in the gastric microbiome and H. pylori infection status. The overall composition of the gastric microbiota in H. pylori‐infected individuals was distinctly different from the negative controls; H. pylori became the dominant species after colonizing the human stomach and significantly decreased the α‐diversity of the gastric community (P 0.05, Wilcoxon rank‐sum test). This study revealed alterations in gastric microbial taxa and function associated with HPI in the Chinese population, which provides an insight into gastric microbial interactions and their potential role in the pathological process of gastric diseases.

ABSTRACTAdequate levels of essential vitamins are important for the prevention of diabetes. While the main efforts to address this are currently focused on the intake of vitamin supplements, improving and maintaining intrinsic vitamin production capacity, which is determined by gut microbes, has received insufficient attention. In this study, we systematically investigated the relationship between gut microbial vitamin production and factors related to diabetes and cardiometabolic health in a deeply phenotyped cohort, Lifelines-DEEP (N = 1,135). We found that blood glucose–related factors, lipids, circulating inflammation, and fecal short-chain fatty acids are associated with gut microbial vitamin production. Use of laxatives and metformin are associated with increased levels of vitamin B1/B6 biosynthesis pathways. We further reveal a mediatory role for microbial vitamin B1/B2 production on the influence of fruit intake on diabetes risk. This study provides preliminary evidence for microbiome-targeted vitamin metabolism interventions to promote health.

Abstract Helicobacter pylori is a causative pathogen of many gastric and extra-gastric diseases. It has infected about half of the global population. There were no genome-wide association studies (GWAS) for H. pylori infection conducted in Chinese population, who carried different and relatively homogenous strain of H. pylori. In this work, we performed SNP (single nucleotide polymorphism)-based, gene-based and pathway-based genome-wide association analyses to investigate the genetic basis of host susceptibility to H. pylori infection in 480 Chinese individuals. We also profiled the composition and function of the gut microbiota between H. pylori infection cases and controls. We found several genes and pathways associated with H. pylori infection (P

Corylus heterophylla (2n = 22) is the most widely distributed, unique, and economically important nut species in China. Chromosome-level genomes of C. avellana, C. heterophylla, and C. mandshurica have been published in 2021, but a satisfactory hazelnut genome database is absent. Northeast China is the main distribution and cultivation area of C. heterophylla, and the mechanism underlying the adaptation of C. heterophylla to extremely low temperature in this area remains unclear. Using single-molecule real-time sequencing and the chromosomal conformational capture (Hi-C) assisted genome assembly strategy, we obtained a high-quality chromosome-scale genome sequence of C. heterophylla, with a total length of 343 Mb and scaffold N50 of 32.88 Mb. A total of 94.72% of the test genes from the assembled genome could be aligned to the Embryophyta_odb9 database. In total, 22,319 protein-coding genes were predicted, and 21,056 (94.34%) were annotated in the assembled genome. A HazelOmics online database (HOD) containing the assembled genome, gene-coding sequences, protein sequences, and various types of annotation information was constructed. This database has a user-friendly and straightforward interface. In total, 439 contracted genes and 3,810 expanded genes were identified through genome evolution analysis, and 17 expanded genes were significantly enriched in the unsaturated fatty acid biosynthesis pathway (ko01040). Transcriptome analysis results showed that FAD (Cor0058010.1), SAD (Cor0141290.1), and KAT (Cor0122500.1) with high expression abundance were upregulated at the ovule maturity stage. We deduced that the expansion of these genes may promote high unsaturated fatty acid content in the kernels and improve the adaptability of C. heterophylla to the cold climate of Northeast China. The reference genome and database will be beneficial for future molecular breeding and gene function studies in this nut species, as well as for evolutionary research on species of the order Fagales.

AimTo investigate clinical and computed tomography (CT) radiomics nomogram for preoperative differentiation of lung adenocarcinoma (LAC) from lung tuberculoma (LTB) in patients with pulmonary solitary solid nodule (PSSN).Materials and MethodsA total of 313 patients were recruited in this retrospective study, including 96 pathologically confirmed LAC and 217 clinically confirmed LTB. Patients were assigned at random to training set (n = 220) and validation set (n = 93) according to 7:3 ratio. A total of 2,589 radiomics features were extracted from each three-dimensional (3D) lung nodule on thin-slice CT images and radiomics signatures were built using the least absolute shrinkage and selection operator (LASSO) logistic regression. The predictive nomogram was established based on radiomics and clinical features. Decision curve analysis was performed with training and validation sets to assess the clinical usefulness of the prediction model.ResultsA total of six clinical features were selected as independent predictors, including spiculated sign, vacuole, minimum diameter of nodule, mediastinal lymphadenectasis, sex, and age. The radiomics nomogram of lung nodules, consisting of 15 selected radiomics parameters and six clinical features showed good prediction in the training set [area under the curve (AUC), 1.00; 95% confidence interval (CI), 0.99–1.00] and validation set (AUC, 0.99; 95% CI, 0.98–1.00). The nomogram model that combined radiomics and clinical features was better than both single models (p < 0.05). Decision curve analysis showed that radiomics features were beneficial to clinical settings.ConclusionThe radiomics nomogram, derived from unenhanced thin-slice chest CT images, showed favorable prediction efficacy for differentiating LAC from LTB in patients with PSSN.

Microbes live in complex communities that are of major importance for environmental ecology, public health, and animal physiology and pathology. Short-read metagenomic shotgun sequencing is currently the state-of-the-art technique for exploring these communities. With the aid of metagenomics, our understanding of the microbiome is moving from composition toward functionality, even down to the genetic variant level. While the exploration of single-nucleotide variation in a genome is a standard procedure in genomics, and many sophisticated tools exist to perform this task, identification of genetic variation in metagenomes remains challenging. Major factors that hamper the widespread application of variant-calling analysis include low-depth sequencing of individual genomes (which is especially significant for the microorganisms present in low abundance), the existence of large genomic variation even within the same species, the absence of comprehensive reference genomes, and the noise introduced by next-generation sequencing errors. Some bioinformatics tools, such as metaSNV or InStrain, have been created to identify genetic variants in metagenomes, but the performance of these tools has not been systematically assessed or compared with the variant callers commonly used on single or pooled genomes. In this study, we benchmark seven bioinformatic tools for genetic variant calling in metagenomics data and assess their performance. To do so, we simulated metagenomic reads to mimic human microbial composition, sequencing errors, and genetic variability. We also simulated different conditions, including low and high depth of coverage and unique or multiple strains per species. Our analysis of the simulated data shows that probabilistic method-based tools such as HaplotypeCaller and Mutect2 from the GATK toolset show the best performance. By applying these tools to longitudinal gut microbiome data from the Human Microbiome Project, we show that the genetic similarity between longitudinal samples from the same individuals is significantly greater than the similarity between samples from different individuals. Our benchmark shows that probabilistic tools can be used to call metagenomes, and we recommend the use of GATK’s tools as reliable variant callers for metagenomic samples.

Helicobacter pylori infection (HPI) is a prevalent infectious disease associated with gastric ulcer, gastric cancer, and many nongastrointestinal disorders. To identify genes that may serve as microbial markers for HPI, we performed shotgun metagenomic sequencing of fecal samples from 313 Chinese volunteers who had undergone a C14 breath test. Through comparing differences in intestinal microbial community structure between H. pylori‐positive and H. pylori‐negative individuals, we identified 58 HPI‐associated microbial species (P

Task-oriented modular design and safety monitoring are demonstrated to be outstanding challenges for robots in practical application. In order to obtain better flexibility and better obstacles avoidance capability, design and analysis of a modular cable-driven parallel robot (MCDPR) are presented in this paper, which can be reconfigured to several configurations in engineering applications by changing the number of the mobile modules and the connection mode of the end effector. With regard to the motion control and safety monitoring system, the design and implementation of hardware and software are presented. An experimental prototype for the MCDPR is developed, followed by a brief illustration of the connection mode between the end effector and cables, and the installation of monitoring nodes. The performance of the MCDPR is discussed experimentally, including real-time pose monitoring and obstacle avoidance. The results verify the feasibility and efficiency of kinematics model and obstacle avoidance method, and the results also indicate that the designed motion control and safety monitoring system can realize trajectory tracking control, real-time safety monitoring, and obstacle avoidance for the MCDPR.

This paper presents the development and feedback force control of a safe, lightweight, yet powerful, and stable passive force feedback data glove (FFDG), utilizing a disc-type magnetorheological (MR) brake as the force feedback device. Firstly, a detailed illustration of the mechanical design of the FFDG, including transmission structure, MR brake, and angle measuring mechanism, is presented. Then, to achieve a precise feedback force control, the design and modelling of a current controller based on the buck circuit are carried out. This is followed by the tracking control of the feedback force, using conventional PID and adaptive fuzzy-PID control schemes. The control effect of the two methods is evaluated and compared through simulations. Finally, an experimental set-up is established, and a series of experiments are carried out on both the manufactured MR brake and the FFDG prototype. The results verify the feasibility and stability of the developed FFDG, and demonstrate that the feedback force tracking accuracy of the adaptive fuzzy-PID controller is satisfactory.

Objective This study was performed to investigate the effects of age and sex on 10 salivary steroid hormones and analyze the correlations between salivary and plasma hormones. Methods The concentrations of 10 salivary steroid hormones in 1090 Chinese adult volunteers were examined using liquid chromatography–tandem mass spectrometry, and a related investigation was performed on the concentrations of salivary hormones in this population. Results The concentrations of androstenedione (A4), 17α-hydroxyprogesterone (17-OHP), aldosterone (ALD), cortisone (COR), corticosterone (CORT), cortisol (F), progesterone (P), and testosterone were significantly different between men and women (Student’s t-test). Differences in 17-OHP and ALD concentrations were highly significant between women in the follicular and luteal phases of their menstrual cycle (Student’s t-test). Five salivary steroid hormones (17-OHP, A4, CORT, COR, and F) significantly decreased with increasing age (Kruskal–Wallis test). A high linear correlation between salivary and plasma 17-OHP, P, A4, and F were observed with obvious sex-related differences (Pearson’s correlation, r > 0.7). Conclusions Our results provide important knowledge regarding the descriptive characteristics of salivary hormones in relation to age and sex and their correlations with plasma hormones.

Objective We compared the salivary nontargeted metabolite profiles between patients with recurrent aphthous ulcer (RAU) and healthy individuals to investigate the metabolic alterations associated with RAU. Methods Saliva samples were collected from 45 patients with RAU and 49 healthy individuals, and the salivary metabolites were quantified using liquid chromatography–tandem mass spectrometry. The metabolomic profiles were then analyzed using multivariate and univariate statistical methods, and enrichment of the metabolites in various biological pathways was assessed. Results In total, 206 significant differentiating metabolites (Wilcoxon test, false discovery rate [FDR] of 0.9). Principal component analysis and partial least-squares discriminant analysis revealed metabolic perturbations involving RAU, and receiver operating characteristic curve analysis with several metabolites showed good diagnostic ability for RAU. Conclusions The results of this study indicate that patients with RAU are characterized by metabolic imbalances. Psychogenic factors, endocrinopathies, and immunosuppression may contribute to the onset of RAU.

To meet the requirements in terms of large workspace, low inertia, and high degree of accuracy, a novel palletizing robot is introduced in this article. Utilizing spatial hybrid cable-actuated serial–parallel structure and parallelogram mechanism, the robot is able to achieve favorable potentials for stiffness, modularity, and reconfigurability. The kinematics and statics of the robot are investigated, and an algorithm is subsequently proposed to calculate the workspace of the limited degree of freedom cable-actuated serial–parallel manipulator. Then the workspace of the robot under different loads is calculated, and the topological properties of the workspace under different loads are compared and analyzed in detail. The results demonstrate that the proposed structure significantly enlarges the workspace and can also complete palletizing tasks effectively.

Dynamic characteristics of the priority control system are of great influence to the control effect, response speed, and working stability of the high-speed on–off digital valve. The main focus of this study is on revealing the dynamic properties of the priority control system for a developed high-speed on–off digital valve. In this article, a detailed introduction to the high-speed on–off digital valve and its priority control system is performed first, which includes the system function, structural composition, and operation principle. Thereafter, a simulation model of the priority control system is established using the AMESim software and the dynamic characteristics are simulated. Simulation results including the variations in the pulse-width modulation signal, coil current, and the main spool displacement of the directional valve are presented and discussed. They indicate that the opening time of the main spool increases with the duty ratio of the voltage signal. Moreover, the main spool displacement is basically equal in one single pulse-width modulation signal cycle, and thus, it is proportional to the cycle number of the pulse-width modulation signal. As a consequence, the priority control system possesses a good dynamic characteristic for the high-speed on–off digital valve as a pilot valve to achieve proportional control of main spool displacement for the directional valve.

In order to transport materials flexibly and smoothly in a tight plant environment, an omni-directional mobile robot based on four Mecanum wheels was designed. The mechanical system of the mobile robot is made up of three separable layers so as to simplify its combination and reorganization. Each modularized wheel was installed on a vertical suspension mechanism, which ensures the moving stability and keeps the distances of four wheels invariable. The control system consists of two-level controllers that implement motion control and multi-sensor data processing, respectively. In order to make the mobile robot navigate in an unknown semi-structured indoor environment, the data from a Kinect visual sensor and four wheel encoders were fused to localize the mobile robot using an extended Kalman filter with specific processing. Finally, the mobile robot was integrated in an intelligent manufacturing system for material conveying. Experimental results show that the omni-directional mobile robot can move stably and autonomously in an indoor environment and in industrial fields.