RMBase v3.0: decode the landscape, mechanisms and functions of RNA modifications.

Although over 170 chemical modifications have been identified, their prevalence, mechanism and function remain largely unknown. To enable integrated analysis of diverse RNA modification profiles, we have developed RMBase v3.0 (http://bioinformaticsscience.cn/rmbase/), a comprehensive platform consisting of eight modules. These modules facilitate the exploration of transcriptome-wide landscape, biogenesis, interactome and functions of RNA modifications. By mining thousands of epitranscriptome datasets with novel pipelines, the 'RNA Modifications' module reveals the map of 73 RNA modifications of 62 species. the 'Genes' module allows to retrieve RNA modification profiles and clusters by gene and transcript. The 'Mechanisms' module explores 23 382 enzyme-catalyzed or snoRNA-guided modified sites to elucidate their biogenesis mechanisms. The 'Co-localization' module systematically formulates potential correlations between 14 histone modifications and 6 RNA modifications in various cell-lines. The 'RMP' module investigates the differential expression profiles of 146 RNA-modifying proteins (RMPs) in 18 types of cancers. The 'Interactome' integrates the interactional relationships between 73 RNA modifications with RBP binding events, miRNA targets and SNPs. The 'Motif' illuminates the enriched motifs for 11 types of RNA modifications identified from epitranscriptome datasets. The 'Tools' introduces a novel web-based 'modGeneTool' for annotating modifications. Overall, RMBase v3.0 provides various resources and tools for studying RNA modifications.

tModBase: deciphering the landscape of tRNA modifications and their dynamic changes from epitranscriptome data.

tRNA molecules contain dense, abundant modifications that affect tRNA structure, stability, mRNA decoding and tsRNA formation. tRNA modifications and related enzymes are responsive to environmental cues and are associated with a range of physiological and pathological processes. However, there is a lack of resources that can be used to mine and analyse these dynamically changing tRNA modifications. In this study, we established tModBase (https://www.tmodbase.com/) for deciphering the landscape of tRNA modification profiles from epitranscriptome data. We analysed 103 datasets generated with second- and third-generation sequencing technologies and illustrated the misincorporation and termination signals of tRNA modification sites in ten species. We thus systematically demonstrate the modification profiles across different tissues/cell lines and summarize the characteristics of tRNA-associated human diseases. By integrating transcriptome data from 32 cancers, we developed novel tools for analysing the relationships between tRNA modifications and RNA modification enzymes, the expression of 1442 tRNA-derived small RNAs (tsRNAs), and 654 DNA variations. Our database will provide new insights into the features of tRNA modifications and the biological pathways in which they participate.

ChIPBase v3.0: the encyclopedia of transcriptional regulations of non-coding RNAs and protein-coding genes.

Non-coding RNAs (ncRNAs) are emerging as key regulators of various biological processes. Although thousands of ncRNAs have been discovered, the transcriptional mechanisms and networks of the majority of ncRNAs have not been fully investigated. In this study, we updated ChIPBase to version 3.0 (https://rnasysu.com/chipbase3/) to provide the most comprehensive transcriptional regulation atlas of ncRNAs and protein-coding genes (PCGs). ChIPBase has identified ∼151 187 000 regulatory relationships between ∼171 600 genes and ∼3000 regulators by analyzing ∼55 000 ChIP-seq datasets, which represent a 30-fold expansion. Moreover, we de novo identified ∼29 000 motif matrices of transcription factors. In addition, we constructed a novel 'Enhancer' module to predict ∼1 837 200 regulation regions functioning as poised, active or super enhancers under ∼1300 conditions. Importantly, we constructed exhaustive coexpression maps between regulators and their target genes by integrating expression profiles of ∼65 000 normal and ∼15 000 tumor samples. We built a 'Disease' module to obtain an atlas of the disease-associated variations in the regulation regions of genes. We also constructed an 'EpiInter' module to explore potential interactions between epitranscriptome and epigenome. Finally, we designed 'Network' module to provide extensive and gene-centred regulatory networks. ChIPBase will serve as a useful resource to facilitate integrative explorations and expand our understanding of transcriptional regulation.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

ZmELF6-ZmPRR37 module regulates maize flowering and salt response.

The control of flowering time in maize is crucial for reproductive success and yield, and it can be influenced by environmental stresses. Using the approaches of Ac/Ds transposon and transposable element amplicon sequencing techniques, we identified a Ds insertion mutant in the ZmPRR37 gene. The Ds insertion showed a significant correlation with days to anthesis. Further research indicated that ZmPRR37-CR knockout mutants exhibited early flowering, whereas ZmPRR37-overexpression lines displayed delayed flowering compared to WT under long-day (LD) conditions. We demonstrated that ZmPRR37 repressed the expression of ZmNF-YC2 and ZmNF-YA3 to delay flowering. Association analysis revealed a significant correlation between flowering time and a SNP2071-C/T located upstream of ZmPRR37. The SNP2071-C/T impacted the binding capacity of ZmELF6 to the promoter of ZmPRR37. ZmELF6 also acted as a flowering suppressor in maize under LD conditions. Notably, our study unveiled that ZmPRR37 can enhance salt stress tolerance in maize by directly regulating the expression of ABA-responsive gene ZmDhn1. ZmDhn1 negatively regulated maize salt stress resistance. In summary, our findings proposed a novel pathway for regulating photoperiodic flowering and responding to salt stress based on ZmPRR37 in maize, providing novel insights into the integration of abiotic stress signals into floral pathways.

CircZNF609 sponges miR-135b to up-regulate SEMA3A expression to alleviate ox-LDL-induced atherosclerosis.

The initiation and progression of atherosclerotic plaque caused by abnormal lipid metabolism is one of the main causes of atherosclerosis (AS). Lipid droplet accumulation has become a novel research pointcut for AS treatment in recent years. In AS patients, miR-135b level was up-regulated relative to the normal cases, which showed negative correlations with the levels of Semaphorin 3A (SEMA3A) and circZNF609, separately. The U937-derived macrophages were cultured with ox-LDL to establish AS models in vitro. After that, the lipid accumulation, inflammation, mitochondrial dysfunction and cell death were evaluated by ORO, ELISA, RT-qPCR, western blot, JC-1 and FCM assays respectively. Transfection of the circZNF609 expression vector notably declined lipid accumulation, attenuated inflammation, reduced mitochondrial dysfunction and inhibited cell death in ox-LDL-stimulated cells. The direct binding of miR-135b to circZNF609 in vitro was confirmed using RIP assay, and SEMA3A expression was up-regulated by circZNF609 overexpression. After manipulating the endogenous expressions of circZNF609, miR-135b and SEMA3A, the above damages in ox-LDL-stimulated cells were rescued by inhibition of miR-135b expression and overexpression of circZNF609 or SEMA3A. Besides, the AS mice model was built to demonstrate the excessive lipid accumulation, increasing inflammation and cell death in AS pathogenesis according to the results of HE staining, ELISA and IHC assays, while these damages were reversed after overexpression of circZNF609 or SEMA3A. In AS models, overexpressed circZNF609 prevents the AS progression through depleting miR-135b expression and subsequent up-regulation of SEMA3A expression to overwhelm lipid accumulation, mitochondrial dysfunction and cell death.

Controllable Pyridine N-Oxidation-Nucleophilic Dechlorination Process for Enhanced Dechlorination of Chloropyridines: The Cooperation of HCO4- and HO2.

Dechlorination of chloropyridines can eliminate their detrimental environmental effects. However, traditional dechlorination technology cannot efficiently break the C-Cl bond of chloropyridines, which is restricted by the uncontrollable nonselective species. Hence, we propose the carbonate species-activated hydrogen peroxide (carbonate species/H2O2) process wherein the selective oxidant (peroxymonocarbonate ion, HCO4-) and selective reductant (hydroperoxide anion, HO2-) controllably coexist by manipulation of reaction pH. Taking 2-chloropyridine (Cl-Py) as an example, HCO4- first induces Cl-Py into pyridine N-oxidation intermediates, which then suffer from the nucleophilic dechlorination by HO2-. The obtained dechlorination efficiencies in the carbonate species/H2O2 process (32.5-84.5%) based on the cooperation of HCO4- and HO2- are significantly higher than those in the HO2--mediated sodium hydroxide/hydrogen peroxide process (0-43.8%). Theoretical calculations confirm that pyridine N-oxidation of Cl-Py can effectively lower the energy barrier of the dechlorination process. Moreover, the carbonate species/H2O2 process exhibits superior anti-interference performance and low electric energy consumption. Furthermore, Cl-Py is completely detoxified via the carbonate species/H2O2 process. More importantly, the carbonate species/H2O2 process is applicable for efficient dehalogenation of halogenated pyridines and pyrazines. This work offers a simple and useful strategy to enhance the dehalogenation efficiency of halogenated organics and sheds new insights into the application of the carbonate species/H2O2 process in practical environmental remediation.

The joint impact of PM2.5 constituents on the risk of cerebrovascular diseases hospitalization: A large community-based cohort study.

Air pollution poses significant health risks to urban areas, with limited focus on the chronic association of PM2.5 and its constituents on cerebrovascular diseases (CERs), especially regarding the joint associations. This study explores the individual and joint associations between PM2.5 constituents and CER hospitalization risks through a cohort analysis of 36,271 adults in the Pearl River Delta, South China, from 2015 to 2020. Cox proportional hazards regression and quantile-based g-computation models were used to quantify the individual and joint associations of annual mean concentrations of PM2.5 constituents with hospitalization for CERs. 1151 participants were hospitalized due to CERs during the five-year follow-up period. Joint associations analyses identified that one quartile increase in co-exposure may result in hazard ratios of 1.530 (1.441-1.623), 1.840 (1.710-1.980), and 1.609 (1.491-1.737) for CERs, total, and ischemic stroke hospitalization, respectively. The adverse effect was primarily driven by organic matter and chlorine. Men, those with a history of tobacco or alcohol use or with low residential greenness, were more susceptible to CERs hospitalization following PM2.5 constituents co-exposure. Upcoming strategies should focus on monitoring and regulating PM2.5 constituents, encouraging healthy lifestyles, and enhancing urban greenery.

Pol3Base: a resource for decoding the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs.

RNA polymerase III (Pol III) transcribes hundreds of non-coding RNA genes (ncRNAs), which involve in a variety of cellular processes. However, the expression, functions, regulatory networks and evolution of these Pol III-transcribed ncRNAs are still largely unknown. In this study, we developed a novel resource, Pol3Base (http://rna.sysu.edu.cn/pol3base/), to decode the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs. The current release of Pol3Base includes thousands of regulatory relationships between ∼79 000 ncRNAs and transcription factors by mining 56 ChIP-seq datasets. By integrating CLIP-seq datasets, we deciphered the interactions of these ncRNAs with >240 RNA binding proteins. Moreover, Pol3Base contains ∼9700 RNA modifications located within thousands of Pol III-transcribed ncRNAs. Importantly, we characterized expression profiles of ncRNAs in >70 tissues and 28 different tumor types. In addition, by comparing these ncRNAs from human and mouse, we revealed about 4000 evolutionary conserved ncRNAs. We also identified ∼11 403 tRNA-derived small RNAs (tsRNAs) in 32 different tumor types. Finally, by analyzing somatic mutation data, we investigated the mutation map of these ncRNAs to help uncover their potential roles in diverse diseases. This resource will help expand our understanding of potential functions and regulatory networks of Pol III-transcribed ncRNAs.

tsRFun: a comprehensive platform for decoding human tsRNA expression, functions and prognostic value by high-throughput small RNA-Seq and CLIP-Seq data.

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation.

ColorCells: a database of expression, classification and functions of lncRNAs in single cells.

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

BACKGROUND: The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. METHODS: We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. RESULTS: In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). CONCLUSIONS: Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

Multi-disciplinary cooperation for the micro-elimination of hepatitis C in China: a hospital-based experience.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the main causes of liver cancer and imposes an enormous social and economic burden. The blood-borne virus screening policy for preventing iatrogenic infections renders hospitals important for identifying individuals infected with hepatitis C. Therefore, we aimed to investigate the establishment of a multi-disciplinary cooperation model in medical institutions to leverage the screening results of patients with hepatitis C. Our objective is to ensure that patients receive timely and effective diagnosis and treatment, thereby enabling the elimination of hepatitis C by 2030. METHOD: A multi-disciplinary cooperation model was established in October 2021. This retrospective study was based on the establishment of antibody-positive and HCV RNA-positive patient databases. A Chi-square test was used to compare the HCV RNA confirmation rate in anti-HCV-positive patients, as well as the hepatitis C diagnosis rate and treatment rate in RNA-positive patients before and after the multi-disciplinary cooperation. A multivariable logistic regression was used to analyse the factors affecting the treatment of patients with hepatitis C. In addition, we examined changes in the level of hepatitis C knowledge among medical staff. RESULTS: After the implementation of the multi-disciplinary cooperation model, the RNA confirmation rate of hepatitis C antibody-positive patients increased from 36.426% to 88.737%, the diagnostic accuracy rate of RNA-positive patients increased from 67.456% to 98.113%, and the treatment rate of patients with hepatitis C increased from 12.426% to 58.491%. Significant improvements were observed among the clinicians regarding their ability to understand the characteristics of hepatitis C (93.711% vs. 58.861%), identify people at high risk (94.340% vs. 53.797%), manage patients with hepatitis C after diagnosis (88.679% vs. 67.089%), and effectively treat hepatitis C (84.277% vs. 51.899%). Multi-disciplinary cooperation in medical institutions was the most important factor for patients to undergo HCV treatment (odds ratio: 0.024, 95% confidence interval: 0.007-0.074). CONCLUSIONS: This study showed that the use of a multi-disciplinary cooperation model to utilise the results of HCV antibody screening fully in patients through further tracking, referral, and treatment may facilitate the detection and treatment of patients with hepatitis C and accelerate the elimination of HCV in China.

Targeted Decomplexation of Metal Complexes for Efficient Metal Recovery by Ozone/Percarbonate.

Traditional methods cannot efficiently recover Cu from Cu(II)-EDTA wastewater and encounter the formation of secondary contaminants. In this study, an ozone/percarbonate (O3/SPC) process was proposed to efficiently decomplex Cu(II)-EDTA and simultaneously recover Cu. The results demonstrate that the O3/SPC process achieves 100% recovery of Cu with the corresponding kobs value of 0.103 min-1 compared with the typical •OH-based O3/H2O2 process (81.2%, 0.042 min-1). The carbonate radical anion (CO3•-) is generated from the O3/SPC process and carries out the targeted attack of amino groups of Cu(II)-EDTA for decarboxylation and deamination processes, resulting in successive cleavage of Cu-O and Cu-N bonds. In comparison, the •OH-based O3/H2O2 process is predominantly responsible for the breakage of Cu-O bonds via decarboxylation and formic acid removal. Moreover, the released Cu(II) can be transformed into stable copper precipitates by employing an endogenous precipitant (CO32-), accompanied by toxic-free byproducts in the O3/SPC process. More importantly, the O3/SPC process exhibits excellent metal recovery in the treatment of real copper electroplating wastewater and other metal-EDTA complexes. This study provides a promising technology and opens a new avenue for the efficient decomplexation of metal-organic complexes with simultaneous recovery of valuable metal resources.

Prenatal exposure to famine and the development of diabetes later in life: an age-period-cohort analysis of the China health and nutrition survey (CHNS) from 1997 to 2015.

PURPOSE: Prenatal exposure to famine has been linked to increased diabetes risk in adulthood. However, one fundamental issue to be addressed is that the reported famine-diabetes relation may be confounded by the age differences between the exposed and non-exposed groups. We aimed to determine the association between prenatal exposure to the Chinese famine of 1959-1962 and risk of diabetes by applying age well-controlled strategies. METHODS: Among 20,535 individuals born in 1955-1966 who participated in the China Health and Nutrition Survey from 1997 to 2015, we constructed age-matched exposed vs. non-exposed groups to investigate the role of prenatal exposure to the Chinese famine of 1959-1962 in relation to diabetes. We also built a hierarchical age-period-cohort (HAPC) model to specifically examine the relation of famine to diabetes risk independent of age. RESULTS: Compared to the age-balanced men in the non-exposed group, the exposed men born in 1961 had a 154% increased risk of diabetes [odds ratio (OR) 2.54 (95% CI 1.07-6.03), P = 0.04). In the HAPC analysis, the predicted probabilities of diabetes peaked in the 1961-birth cohort of men [3.4% (95% CI 2.4%-5.0%)], as compared to the average probability of diabetes (reference) of 1.8% for men overall. Neither analytical strategy revealed any strong relation between famine exposure and diabetes risk in women. CONCLUSION: Among the pre-defined Chinese famine period of 1959-1962, early-life exposure to famine was associated with increased diabetes risk in men but not in women, and these relations were independent of age.

deepBase v3.0: expression atlas and interactive analysis of ncRNAs from thousands of deep-sequencing data.

Eukaryotic genomes encode thousands of small and large non-coding RNAs (ncRNAs). However, the expression, functions and evolution of these ncRNAs are still largely unknown. In this study, we have updated deepBase to version 3.0 (deepBase v3.0, http://rna.sysu.edu.cn/deepbase3/index.html), an increasingly popular and openly licensed resource that facilitates integrative and interactive display and analysis of the expression, evolution, and functions of various ncRNAs by deeply mining thousands of high-throughput sequencing data from tissue, tumor and exosome samples. We updated deepBase v3.0 to provide the most comprehensive expression atlas of small RNAs and lncRNAs by integrating ∼67 620 data from 80 normal tissues and ∼50 cancer tissues. The extracellular patterns of various ncRNAs were profiled to explore their applications for discovery of noninvasive biomarkers. Moreover, we constructed survival maps of tRNA-derived RNA Fragments (tRFs), miRNAs, snoRNAs and lncRNAs by analyzing >45 000 cancer sample data and corresponding clinical information. We also developed interactive webs to analyze the differential expression and biological functions of various ncRNAs in ∼50 types of cancers. This update is expected to provide a variety of new modules and graphic visualizations to facilitate analyses and explorations of the functions and mechanisms of various types of ncRNAs.

A Novel Ultrasound Robot with Force/torque Measurement and Control for Safe and Efficient Scanning.

Medical ultrasound is of increasing importance in medical diagnosis and intraoperative assistance and possesses great potential advantages when integrated with robotics. However, some concerns, including the operation efficiency, operation safety, image quality, and comfort of patients, remain after introducing robotics into medical ultrasound. In this paper, an ultrasound robot integrating a force control mechanism, force/torque measurement mechanism, and online adjustment method, is proposed to overcome the current limitations. The ultrasound robot can measure operating forces and torques, provide adjustable constant operating forces, eliminate great operating forces introduced by accidental operations, and achieve various scanning depths based on clinical requirements. The proposed ultrasound robot would potentially facilitate sonographers to find the targets quickly, improve operation safety and efficiency, and decrease patients' discomfort. Simulations and experiments were carried out to evaluate the performance of the ultrasound robot. Experimental results show that the proposed ultrasound robot is able to detect operating force in the z-direction and torques around the x- and y- directions with errors of 3.53% F.S., 6.68% F.S., and 6.11% F.S., respectively, maintain the constant operating force with errors of less than 0.57N, and achieve various scanning depths for target searching and imaging. This proposed ultrasound robot has good performance and would potentially be used in medical ultrasound.

SAPM: Self-Adaptive Parallel Manipulator with Pose and Force Adjustment for Robotic Ultrasonography.

Robotic ultrasonography potentially acts as an essential aid to medical diagnosis. To overcome the limitations in robotic ultrasonography, in this paper, we proposed a novel self-adaptive parallel manipulator (SAPM) that can automatically adjust the ultrasound (US) probe pose to adapt to various contours of scanned areas, provide approximate constant operating forces/torques, achieve mechanical measurement, and cushion undesired produced forces. A novel parallel adjustment mechanism is proposed to attain automatic pose adjustment with 3 degrees of freedom (DOFs). This mechanism enables the US probe to adapt to different scanned areas and to perform the scanning with approximate constant forces and torques. Besides, we present a mechanical measurement and safety protection method that can be integrated into the SAPM and used as operation status monitoring and early warning during scanning procedures by capturing operating forces and torques. Experiments were carried out to calibrate the measurement and buffer units and evaluate the performance of the SAPM. Experimental results show the ability of the SAPM to provide 3-DoFs motion and operating force/torque measurement and automatically adjust the US probe pose to capture US images of equally good quality compared to a manual sonographer scan. Moreover, it has characteristics similar to soft robots that could significantly improve operation safety, and could be extended to some other engineering or medical applications.

[Effect of Rhizophagus intraradices on growth of Salvia miltiorrhiza].

The study aimed to explore the effects of inoculation of Rhizophagus intraradices on the biomass, effective component content, and endogenous hormone content of Salvia miltiorrhiza through pot experiments. The number of leaves, plant height, dry weight of aboveground and underground parts, branch number, root number, root length, root diameter, and other biomass were mea-sured by weighing and counting methods. The content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, tanshinone Ⅱ_A, cryptotanshinone, and other effective components was determined by ultra-high performance liquid chromatography. The content of ABA and GA_3 was determined by triple quadrupole mass spectrometry. The correlations between biomass and effective components and between effective components and plant hormones ABA and GA_3 were analyzed. The results showed that R. intraradices significan-tly increased the aboveground dry weight, leaf number, and root number of S. miltiorrhiza by 0.24-0.65 times, respectively. The content of salvianolic acid B and rosmarinic acid in the aboveground part and the content of salvianolic acid B, caffeic acid, rosmarinic acid, tanshinone Ⅰ, and tanshinone Ⅱ_A in the underground part were significantly increased by 0.44-1.78 times, respectively. R. intraradices infection significantly increased the GA_3/ABA values of aboveground and underground parts by 3.82 and 76.47 times, respectively. The correlation analysis showed that caffeic acid, the effective component of the aboveground part, was significantly positively correlated with plant height, tanshinone Ⅱ_A, the effective component of the underground part, was significantly positively correlated with biomass root number, cryptotanshinone, and dry weight, while rosmarinic acid was significantly negatively correlated with dry weight. There were significant positive correlations between cryptotanshinone and ABA, tanshinone Ⅱ_A and ABA and GA_3, and caffeic acid and GA_3. In conclusion, R. intraradices can promote the accumulation of biomass and secondary metabolites of S. miltiorrhiza and regulate the balance between plant hormones ABA and GA_3, thereby promoting the growth of S. miltiorrhiza.

Metabolomic analyses reveal new stage-specific features of COVID-19.

The current pandemic of coronavirus disease 2019 (COVID-19) has affected >160 million individuals to date, and has caused millions of deaths worldwide, at least in part due to the unclarified pathophysiology of this disease. Identifying the underlying molecular mechanisms of COVID-19 is critical to overcome this pandemic. Metabolites mirror the disease progression of an individual and can provide extensive insights into their pathophysiological significance at each stage of disease. We provide a comprehensive view of metabolic characterisation of sera from COVID-19 patients at all stages using untargeted and targeted metabolomic analysis. As compared with the healthy controls, we observed different alteration patterns of circulating metabolites from the mild, severe and recovery stages, in both the discovery cohort and the validation cohort, which suggests that metabolic reprogramming of glucose metabolism and the urea cycle are potential pathological mechanisms for COVID-19 progression. Our findings suggest that targeting glucose metabolism and the urea cycle may be a viable approach to fight COVID-19 at various stages along the disease course.