The SMC5/6 complex recruits the PAF1 complex to facilitate DNA double-strand break repair in Arabidopsis.

DNA double-strand breaks (DSBs) are one of the most toxic forms of DNA damage, which threatens genome stability. Homologous recombination is an error-free DSB repair pathway, in which the evolutionarily conserved SMC5/6 complex (SMC5/6) plays essential roles. The PAF1 complex (PAF1C) is well known to regulate transcription. Here we show that SMC5/6 recruits PAF1C to facilitate DSB repair in plants. In a genetic screen for DNA damage response mutants (DDRMs), we found that the Arabidopsis ddrm4 mutant is hypersensitive to DSB-inducing agents and is defective in homologous recombination. DDRM4 encodes PAF1, a core subunit of PAF1C. Further biochemical and genetic studies reveal that SMC5/6 recruits PAF1C to DSB sites, where PAF1C further recruits the E2 ubiquitin-conjugating enzymes UBC1/2, which interact with the E3 ubiquitin ligases HUB1/2 to mediate the monoubiquitination of histone H2B at DSBs. These results implicate SMC5/6-PAF1C-UBC1/2-HUB1/2 as a new axis for DSB repair through homologous recombination, revealing a new mechanism of SMC5/6 and uncovering a novel function of PAF1C.

Association patterns of ketone bodies with the risk of adverse outcomes according to diabetes status.

AIM: To investigate the associations between ketone bodies (KB) and multiple adverse outcomes including cardiovascular disease (CVD), chronic kidney disease (CKD) and all-cause mortality according to diabetes status. METHODS: This prospective study included 222 824 participants free from CVD and CKD at baseline from the UK Biobank. Total KB including ß-hydroxybutyrate, acetoacetate and acetone were measured by nuclear magnetic resonance. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between KB and adverse outcomes among participants with normoglycaemia, prediabetes and type 2 diabetes, respectively. RESULTS: During a mean follow-up of 14.1 years, 24 088 incident CVD events (including 17 303 coronary heart disease events, 5172 stroke events and 5881 heart failure [HF] events), 8605 CKD events and 15 813 deaths, were documented. Higher total KB significantly increased the risk of HF among participants with normoglycaemia (HR, 1.32 [95% CI, 1.17-1.49], per 10-fold increase in total KB) and prediabetes (1.35 [1.04-1.76]), and increased the risk of CKD among those with normoglycaemia (1.20 [1.09-1.33]). Elevated KB levels were associated with an increased risk of all-cause mortality across the glycaemic spectrum (1.32 [1.23-1.42] for normoglycaemia, 1.45 [1.24-1.71] for prediabetes and 1.47 [1.11-1.94] for diabetes). Moreover, a significant additive interaction between KB and diabetes status was observed on the risk of death (P = .009), with 4.9% of deaths attributed to the interactive effects. CONCLUSIONS: Our study underscored the variation in association patterns between KB and adverse outcomes according to diabetes status and suggested that KB could interact with diabetes status in an additive manner to increase the risk of mortality.

Rapid chemical reduction synthesis of copper nanoclusters with blue fluorescence for highly sensitive detection of furazolidone.

Tannic acid (TA), as a stabilizing agent, was successfully utilized to establish blue-emitting copper nanoclusters (TA-Cu NCs) on the basis of a facile chemical reduction preparation method. Characterization results proved successful synthesis of TA-Cu NCs with uniform size and excellent stability. TA-Cu NCs exhibited a blue emission wavelength at 431 nm when excited at 364 nm. Interestingly, the as-prepared TA-Cu NCs were selectively quenched by furazolidone based on static quenching. In addition, this analysis platform for furazolidone detection had an excellent linear range from 0.5 to 120 µM with a detection limit of 0.074 µM (S/N = 3). Furthermore, the accuracy of this sensing method was successfully confirmed by detecting furazolidone in bovine serum samples, indicating that TA-Cu NCs had bright application prospects.

Histidine-capped copper nanoclusters for in situ amplified fluorescence monitoring of doxycycline through inner filter effect.

There is a significant need to accurately measure doxycycline concentrations in view of the adverse effects of an overdose on human health. A fluorescence (FL) detection method was adopted and copper nanoclusters (CuNCs) were synthesized using chemical reduction technology. Based on FL quenching with doxycycline, the prepared CuNCs were used to explore a fluorescent nanoprobe for doxycycline detection. In an optimal sensing environment, this FL nanosensor was sensitive and selective in doxycycline sensing and displayed a linear relationship in the range 0.5-200 µM with a detection limit of 0.092 µΜ. A characterization test demonstrated that CuNCs offered active functional groups for identifying doxycycline using electrostatic interaction and hydrogen bonds. Static quenching and the inner filter effect (IFE) resulted in weakness in the FL of His@CuNCs with doxycycline with great efficiency. This suggested nanosensor was revealed to be a functional model for simple and rapid detection of doxycycline in real samples with very pleasing accuracy.

Selective detection of nitrofurantoin by histidine-capped silver nanoclusters with blue luminescence.

In view of the significance of nitrofurantoin, there is an urgent need for efficient analytical methods for accurate detection of nitrofurantoin. Considering their superior fluorescence performance and rarity of reports regarding nitrofurantoin detection by fluorescent silver nanoclusters (Ag NCs), Ag NCs with good stability and uniform size were synthesized through a simple method by protection of histidine (His) and reduction of ascorbic acid (AA). Based on the quenching by nitrofurantoin, Ag NCs were applied successfully in the detection of nitrofurantoin with high sensitivity. In the range of 0.5-150 µM, a linear relationship was found between ln(F0 /F) and nitrofurantoin amounts. Static quenching and inner filter effect were proved to be the main quenching mechanisms. Significantly superior selectivity and satisfactory recovery results in bovine serum indicate that Ag NCs provide a better choice for nitrofurantoin detection.

Joint deep learning for batch effect removal and classification toward MALDI MS based metabolomics.

BACKGROUND: Metabolomics is a primary omics topic, which occupies an important position in both clinical applications and basic researches for metabolic signatures and biomarkers. Unfortunately, the relevant studies are challenged by the batch effect caused by many external factors. In last decade, the technique of deep learning has become a dominant tool in data science, such that one may train a diagnosis network from a known batch and then generalize it to a new batch. However, the batch effect inevitably hinders such efforts, as the two batches under consideration can be highly mismatched. RESULTS: We propose an end-to-end deep learning framework, for joint batch effect removal and then classification upon metabolomics data. We firstly validate the proposed deep learning framework on a public CyTOF dataset as a simulated experiment. We also visually compare the t-SNE distribution and demonstrate that our method effectively removes the batch effects in latent space. Then, for a private MALDI MS dataset, we have achieved the highest diagnostic accuracy, with about 5.1 ~ 7.9% increase on average over state-of-the-art methods. CONCLUSIONS: Both experiments conclude that our method performs significantly better in classification than conventional methods benefitting from the effective removal of batch effect.

Positive association of glucagon with bone turnover markers in type 2 diabetes: A cross-sectional study.

AIMS: The osteo-metabolic changes in type 2 diabetes (T2D) patients are intricate and have not been fully revealed. It is not clear whether glucagon is entirely harmful in the pathogenesis of diabetes or a possible endocrine counter-regulation mechanism to reverse some abnormal bone metabolism. This study aimed to investigate the association between glucagon and bone turnover markers (BTMs) in T2D patients. METHODS: A total of 3984 T2D participants were involved in a cross-sectional study in Shanghai, China. Serum glucagon was measured to elucidate its associations with intact N-terminal propeptide of type I collagen (P1NP), osteocalcin (OC), and ß-C-terminal telopeptide (ß-CTX). Glucagon was detected with a radioimmunoassay. Propeptide of type I collagen, OC, and ß-CTX were detected using chemiluminescence. The diagnosis of T2D was based on American Diabetes Association criteria. RESULTS: The concentration of glucagon was positively correlated with two BTMs [OC-ß: 0.034, 95% CI: 0.004, 0.051, p = 0.024; CTX-ß: 0.035, 95% CI: 0.004, 0.062, p = 0.024]. The result of P1NP was [P1NP-regression coefficient (ß): 0.027, 95% CI: -0.003, 0.049, p = 0.083]. In the glucagon tertiles, P for trend of the BTMs is [P1NP: 0.031; OC: 0.038; CTX: 0.020], respectively. CONCLUSIONS: Glucagon had a positive effect on bone metabolism. The concentrations of the three BTMs increased as glucagon concentrations rose. This implied that glucagon might speed up skeletal remodelling, accelerate osteogenesis, and promote the formation of mature bone tissue. At the same time, the osteoclastic process was also accelerated, providing raw materials for osteogenesis to preserve the dynamic balance. In view of the successful use of single-molecule as well as dual/triple agonists, it would be feasible to develop a preparation that would reduce osteoporosis in diabetic patients.

An Efficient System for Ds Transposon Tagging in Brachypodium distachyon.

Transposon tagging is a powerful tool that has been widely applied in several species for insertional mutagenesis in plants. Several efforts have aimed to create transfer-DNA (T-DNA) insertional mutant populations in Brachypodium distachyon, a monocot plant used as a model system to study temperate cereals, but there has been a lack of research aimed at using transposon strategies. Here, we describe the application of a maize (Zea mays) Dissociation (Ds) transposon tagging system in B distachyon The 35S::AcTPase cassette and Ds element were constructed within the same T-DNA and transformed into B distachyon plants. The Ds element was readily transposed to other chromosomes or to the same chromosome under the function of Activator (Ac) transposase. Through homologous chromosome synapsis, recombination, and segregation, the Ds element separated from the Ac element. We selected stable Ds-only plants using G418 and GFP assays and analyzed 241 T0 lines, some of which were highly efficient at producing Ds-only progeny. Through thermal asymmetric interlaced PCR, we isolated 710 independent Ds flanking sequences from Ds-only plants. Furthermore, we identified a large collection of mutants with visible developmental phenotypes via this transposon tagging system. The system is relatively simple and rapid in comparison to traditional T-DNA insertion strategies, because once efficiency lines are obtained they can be reused to generate more lines from nontransposed plants without the use of time-consuming tissue culture steps.

Multicomponent Reaction of Phosphines, Benzynes, and CO2: Facile Synthesis of Stable Zwitterionic Phosphonium Inner Salts.

The first synthesis of benzyne-derived stable zwitterions is reported. Benzynes generated in situ from 2-(trimethylsilyl)aryl triflates undergo a multicomponent reaction with phosphines and CO2 to produce the stable 1,5-zwitterionic species in moderate to excellent isolated yields, which provides a novel method for the preparation of phosphonium inner salts under mild and transition-metal-free conditions.

Functional conservation and diversification of APETALA1/FRUITFULL genes in Brachypodium distachyon.

The duplicated grass APETALA1/FRUITFULL (AP1/FUL) genes have distinct but overlapping patterns of expression, suggesting their discrete roles in transition to flowering, specification of spikelet meristem identity and specification of floral organ identity. In this study, we analyzed the expression patterns and functions of four AP1/FUL paralogs (BdVRN1, BdFUL2, BdFUL3 and BdFUL4) in Brachypodium distachyon, a model plant for the temperate cereals and related grasses. Among the four genes tested, only BdVRN1 could remember the prolonged cold treatment. The recently duplicated BdVRN1 and BdFUL2 genes were expressed in a highly consistent manner and ectopic expressions of them caused similar phenotypes such as extremely early flowering and severe morphological alterations of floral organs, indicating their redundant roles in floral transition, inflorescence development and floral organ identity. In comparison, ectopic expressions of BdFUL3 and BdFUL4 only caused a moderate early flowering phenotype, suggesting their divergent function. In yeast two-hybrid assay, both BdVRN1 and BdFUL2 physically interact with SEP proteins but only BdFUL2 is able to form a homodimer. BdVRN1 also interacts weakly with BdFUL2. Our results indicate that, since the separation of AP1/FUL genes in grasses, the process of sub- or neo-functionalization has occurred and paralogs function redundantly and/or separately in flowering competence and inflorescence development.

Follicle-stimulating hormone is associated with non-alcoholic fatty liver disease in Chinese women over 55 years old.

BACKGROUND AND AIM: Obesity and diabetes are related to non-alcoholic fatty liver disease (NAFLD). A reduction in follicle-stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability. METHODS: Our data were obtained from the 2014 Survey on Prevalence in East China for Metabolic Diseases and Risk Factors. A total of 1635 women at the age of 55-89 years were selected. The degrees of fatty liver were categorized into mild and moderate-severe hepatic steatosis groups by ultrasonography. FSH and other sex hormones were measured by chemiluminescence. RESULTS: A total of 366 (22.4%) and 417 (25.5%) women had mild and moderate-severe hepatic steatosis, respectively. FSH was negatively correlated with waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), and other metabolic factors (all P < 0.05). After adjusting for age, estradiol, and total testosterone, increased quartiles of FSH were associated with significantly decreased odds ratios of mild and moderate-severe groups (both P for trends <0.05). After further adjustment for waist circumference and HOMA-IR, FSH was no longer associated with mild hepatic steatosis. The association of FSH with moderate-severe hepatic steatosis was attenuated by waist circumference and HOMA-IR but persisted in the fully adjusted model (P for trend <0.01). CONCLUSION: Follicle-stimulating hormone was negatively associated with NAFLD in women over 55 years old. Adiposity and insulin resistance explained most of the association of mild hepatic steatosis and partially explained the association of moderate-severe hepatic steatosis with FSH.

Phillyrin, a natural lignan, attenuates tumor necrosis factor α-mediated insulin resistance and lipolytic acceleration in 3T3-L1 adipocytes.

In obese adipose tissue, tumor necrosis factor-α secreted from macrophages plays an important role in the adipocyte dysfunctions, including insulin resistance, lipolytic acceleration, and changes of adipokines, which promote the development of obesity-related complications. Phillyrin, an active ingredient found in many medicinal plants and certain functional foods, elicits anti-obesity and anti-inflammatory properties in vivo. The aim of the current study was to investigate the role of phillyrin in preventing tumor necrosis factor α-induced insulin resistance or lipolytic acceleration in 3T3-L1 adipocytes. Our results showed that phillyrin partially restored insulin-stimulated 2-DOG uptake, which was reduced by tumor necrosis factor-α, with concomitant restoration in serine phosphorylation of insulin receptor substrate-1 and insulin-stimulated Glut4 translocation to plasma membrane. Phillyrin also dose-dependently prevented tumor necrosis factor α-stimulated adipocyte lipolysis with preserved downregulation of perilipin. The mitogen-activated protein kinases and I kappaB kinase activation was promoted in tumor necrosis factor α-stimulated adipocytes, but pretreatment with 40 µM phillyrin inhibited the phosphorylation of extracellular signal-regulated kinases1/2, stress-activated protein kinase/Jun N-terminal kinase and I kappaB kinase (p<0.05). Moreover, phillyrin could inhibit the expressions of interleukin-6 and monocyte chemoattractant protein-1 induced by tumor necrosis factor-α. Using transwell coculture method with 3T3-L1 adipocytes and RAW 264.7 macrophages, the enhanced productions of tumor necrosis factor-α and free fatty acids in the medium were significantly reduced by phillyrin (p<0.05). These results indicate that phillyrin exerts a beneficial effect on adipocyte dysfunctions induced by tumor necrosis factor-α through suppression of the activation of I kappaB kinase and N-terminal kinase. Phillyrin may have the potential to ameliorate the inflammatory changes and insulin resistance in obese adipose tissue.

One-Pot facile synthesis of fluorescent copper nanoclusters for highly selective and sensitive detection of tetracycline.

Due to the excellent characteristics, fluorescent copper nanoclusters (Cu NCs) have aroused great interest in recent years. Herein, the simple prepared, environmentally friendly fluorescent Cu NCs were synthesized by using trypsin as the stabilizer and applied for the determination of tetracycline. Uniformly dispersed Try-Cu NCs were obtained with average size of 3.5 ± 0.3 nm and some excellent merits of good water solubility, UV light stability and salt stability. Emission peaks around 460.0 nm were visibly quenched by tetracycline based on static quenching mechanism and inner filter effect (IFE). Two excellent linear relationships were observed between ln(F0/F) and tetracycline concentrations in the range of 1-100 µM and 100-300 µM with limit of detection (LOD) of 0.084 µM. Meanwhile, this nanoprobe exhibited an apparent selectivity for tetracycline detection. Moreover, Try-Cu NCs were successfully employed to determine tetracycline in serum and milk samples after facile pretreatment with satisfactory recovery rates and credible standard deviation. The results suggested that this as-prepared Try-Cu NCs had excellent application prospects in the future.

Nitrogen Forms Regulate the Response of Microcystis aeruginosa to Nanoplastics at Environmentally Relevant Nitrogen Concentrations.

As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.

MiR-181a contributes to bufalin-induced apoptosis in PC-3 prostate cancer cells.

BACKGROUND: Bufalin is a major active compound of cinobufacini, which comes from dried toad venom and has been used for treatments of various cancers in China for many years. A number of studies have demonstrated that bufalin can induce apoptosis in some cancers. However, effects and mechanism of bufalin on prostate cancer cells remain unknown. METHODS: Apoptosis assay was measured by the annexin-V/PI flow cytometric assay. Western blot was used to measure Caspase-3 and Bcl-2. qRT-PCR was used to measure the relative expression of miR-181a. RESULTS: Bufalin was found to induce the expression of miR-181a, a small non-coding RNA believed to induce apoptosis by repressing its target gene, BCL-2. In prostate cancer PC-3cell line, bufalin-induced apoptosis can be largely attenuated by a miR-181a inhibitor, which blocked bufalin-induced Bcl-2 reduction and caspase-3 activation. CONCLUSIONS: Our dataindicatedthat miR-181a mediates bufalin-induced apoptosis in PC-3 cells. Thus, we presented here a new pharmacological mechanism for bufalin in anti-tumor therapy.

Horizontal and vertical migration of cyanobacterial blooms in two eutrophic lakes observed from the GOCI satellite.

Under the variations of natural conditions (temperature, wind speed, light, et al.) and self-regulation of buoyancy, cyanobacterial blooms can change rapidly in a short time. The Geostationary Ocean Color Imager (GOCI) can provide hourly monitoring of the dynamics of algal blooms (eight times per day), and has potential in observing the horizontal and vertical movement of cyanobacterial blooms. Based on the fractional floating algae cover (FAC), the diurnal dynamics and migration of floating algal blooms were evaluated, and the horizontal and vertical migration speed of phytoplankton was estimated from the proposed algorithm in two eutrophic lakes, Lake Taihu and Lake Chaohu in China. The locations, number, and area of algal bloom patches showed the hotspots and horizontal movement of bloom patches. The spatial and seasonal variations of the vertical velocities indicated that both the rising and sinking speed were higher in summer and autumn than those in spring and winter. The factors affecting diurnal horizontal and vertical migrations of phytoplankton were analyzed. Diffuse horizontal irradiance (DHI), direct normal irradiance (DNI), and temperature had significant positive relationships with FAC in the morning. Wind speed contributed 18.3 and 15.1% to the horizontal movement speed in Lake Taihu and Lake Chaohu, respectively. The rising speed was more related to DNI and DHI in Lake Taihu and Lake Chaohu with contribution of 18.1 and 16.6%. The horizontal and vertical movement of algae provide important information for understanding phytoplankton dynamics and the prediction and warning of algal blooms in lake management.

Effect of Collagenase Chemonucleolysis on Residual Pain After Transforaminal Lumbar Endoscopic Discectomy.

Purpose: To investigate the short-term clinical effect of collagenase chemonucleolysis (CCNL) in the treatment of residual pain after transforaminal lumbar endoscopic discectomy (TLED). Patients and Methods: The clinical data of 40 patients with residual pain after TLED for lumbar disc herniation (LDH) in our hospital from January 2018 to December 2020 were retrospectively analyzed. The visual analogue scale (VAS) and quality of recovery-15 (QoR-15) were used to evaluate the effect of the operation. Modified MacNab method was used to evaluate the efficacy of CCNL at 6 months and 12 months after operation. Results: All patients successfully completed the operation without serious complications, such as intervertebral space infection, vascular injury and nerve injury. The VAS 3 days after TLED was not significantly lower than that Pre-TLED (P > 0.05). The VAS at each time point after CCNL was significantly lower than that at Pre-TLED, and the QoR-15 score at each time point after CCNL was significantly higher than that 3 days after CCNL (P < 0.05). The modified MacNab criteria for the last follow-up was 95%. Conclusion: CCNL can effectively relieve the residual pain after TLED, and the quality of life of patients after TLED is improved with time, and the safety of CCNL is higher.

Unsupervised Landmark Detection-Based Spatiotemporal Motion Estimation for 4-D Dynamic Medical Images.

Motion estimation is a fundamental step in dynamic medical image processing for the assessment of target organ anatomy and function. However, existing image-based motion estimation methods, which optimize the motion field by evaluating the local image similarity, are prone to produce implausible estimation, especially in the presence of large motion. In addition, the correct anatomical topology is difficult to be preserved as the image global context is not well incorporated into motion estimation. In this study, we provide a novel motion estimation framework of dense-sparse-dense (DSD), which comprises two stages. In the first stage, we process the raw dense image to extract sparse landmarks to represent the target organ's anatomical topology, and discard the redundant information that is unnecessary for motion estimation. For this purpose, we introduce an unsupervised 3-D landmark detection network to extract spatially sparse but representative landmarks for the target organ's motion estimation. In the second stage, we derive the sparse motion displacement from the extracted sparse landmarks of two images of different time points. Then, we present a motion reconstruction network to construct the motion field by projecting the sparse landmarks' displacement back into the dense image domain. Furthermore, we employ the estimated motion field from our two-stage DSD framework as initialization and boost the motion estimation quality in light-weight yet effective iterative optimization. We evaluate our method on two dynamic medical imaging tasks to model cardiac motion and lung respiratory motion, respectively. Our method has produced superior motion estimation accuracy compared to the existing comparative methods. Besides, the extensive experimental results demonstrate that our solution can extract well-representative anatomical landmarks without any requirement of manual annotation. Our code is publicly available online: https://github.com/yyguo-sjtu/DSD-3D-Unsupervised-Landmark-Detection-Based-Motion-Estimation.

Relationship between thick or greasy tongue-coating microbiota and tongue diagnosis in patients with primary liver cancer.

Tongue diagnosis is a unique aspect of traditional Chinese medicine for diagnosing diseases before determining proper means of treatment, but it also has the disadvantage of relying on the subjective experience of medical practitioners and lack objective basis. The purpose of this article is to elucidate tongue-coating microbiota and metabolic differences in primary liver cancer (PLC) patients with thick or greasy tongue coatings. Tongue-coating samples were analyzed in 60 PLC patients (30 PLC with thick or greasy tongue-coating patients and 30 PLC with tongue-coating neither thick nor greasy) and 25 healthy controls (HC) using 16S rRNA gene sequencing technology. As compared to healthy individuals, tongue coatings of patients with PLC had elevated levels of Firmicutes and Actinobacteria. The abundance of Fusobacteria, SR1_Absconditabacteria_, and Spirochaete were higher in tongue coatings of healthy controls compared to samples in patients with PLC. In addition to site-specific differences, higher abundances of Fusobacteria and Actinobacteria were observed in thick or greasy tongue-coating patients as compared to non-thick and greasy tongue-coating patients. The inferred metagenomic pathways enriched in the PLC tongue-coating patients were mainly those involved in replication, recombination, and repair of protein. We also identify a tongue-coating microbiome signature to discriminate HC and PLC, including 15 variables on genus level. The prediction performance of the signature showed well in the training and validation cohorts. This research illustrates specific clinical features and bacterial structures in PLC patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.

Relation Regularized Scene Graph Generation.

Scene graph generation (SGG) is built on top of detected objects to predict object pairwise visual relations for describing the image content abstraction. Existing works have revealed that if the links between objects are given as prior knowledge, the performance of SGG is significantly improved. Inspired by this observation, in this article, we propose a relation regularized network (R2-Net), which can predict whether there is a relationship between two objects and encode this relation into object feature refinement and better SGG. Specifically, we first construct an affinity matrix among detected objects to represent the probability of a relationship between two objects. Graph convolution networks (GCNs) over this relation affinity matrix are then used as object encoders, producing relation-regularized representations of objects. With these relation-regularized features, our R2-Net can effectively refine object labels and generate scene graphs. Extensive experiments are conducted on the visual genome dataset for three SGG tasks (i.e., predicate classification, scene graph classification, and scene graph detection), demonstrating the effectiveness of our proposed method. Ablation studies also verify the key roles of our proposed components in performance improvement.