Spatiotemporal Activation of Protein O-GlcNAcylation in Living Cells.

O-linked N-acetylglucosamine (O-GlcNAc) is a prevalent protein modification that plays fundamental roles in both cell physiology and pathology. O-GlcNAc is catalyzed solely by O-GlcNAc transferase (OGT). The study of protein O-GlcNAc function is limited by the lack of tools to control OGT activity with spatiotemporal resolution in cells. Here, we report light control of OGT activity in cells by replacing a catalytically essential lysine residue with a genetically encoded photocaged lysine. This enables the expression of a transiently inactivated form of OGT, which can be rapidly reactivated by photo-decaging. We demonstrate the activation of OGT activity by monitoring the time-dependent increase of cellular O-GlcNAc and profile glycoproteins using mass-spectrometry-based quantitative proteomics. We further apply this activation strategy to control the morphological contraction of fibroblasts. Furthermore, we achieved spatial activation of OGT activity predominantly in the cytosol. Thus, our approach provides a valuable chemical tool to control cellular O-GlcNAc with much needed spatiotemporal precision, which aids in a better understanding of O-GlcNAc function.

COVID-19 Surveiller: toward a robust and effective pandemic surveillance system basedon social media mining.

The outbreak of the novel coronavirus, COVID-19, has become one of the most severe pandemics in human history. In this paper, we propose to leverage social media users as social sensors to simultaneously predict the pandemic trends and suggest potential risk factors for public health experts to understand spread situations and recommend proper interventions. More precisely, we develop novel deep learning models to recognize important entities and their relations over time, thereby establishing dynamic heterogeneous graphs to describe the observations of social media users. A dynamic graph neural network model can then forecast the trends (e.g. newly diagnosed cases and death rates) and identify high-risk events from social media. Based on the proposed computational method, we also develop a web-based system for domain experts without any computer science background to easily interact with. We conduct extensive experiments on large-scale datasets of COVID-19 related tweets provided by Twitter, which show that our method can precisely predict the new cases and death rates. We also demonstrate the robustness of our web-based pandemic surveillance system and its ability to retrieve essential knowledge and derive accurate predictions across a variety of circumstances. Our system is also available at http://scaiweb.cs.ucla.edu/covidsurveiller/. This article is part of the theme issue 'Data science approachs to infectious disease surveillance'.

[Fast Removal of CT Ring Artifacts].

OBJECTIVE: To explore how to remove CT ring-shaped artifact quickly and effectively, and to improve accuracy of CT reconstruction image. METHODS: CT graphics (including the ring-shaped artifacts) were used first in coordinate transformation with a new transformation method. A two-dimensional filter was designed to filter the image. Then, a one-dimensional filter was used to re-filter the image. Finally, a new transform method was used to restore the image. RESULTS: The two-step coordinate transformation of ring-shaped artifact algorithm resulted in accurate restored original CT image, effectively reducing its interference on useful information. CONCLUSION: The method described in this study can overcome disadvantages of existing methods and obtain good results.

An efficient parallel algorithm for accelerating computational protein design.

MOTIVATION: Structure-based computational protein design (SCPR) is an important topic in protein engineering. Under the assumption of a rigid backbone and a finite set of discrete conformations of side-chains, various methods have been proposed to address this problem. A popular method is to combine the dead-end elimination (DEE) and A* tree search algorithms, which provably finds the global minimum energy conformation (GMEC) solution. RESULTS: In this article, we improve the efficiency of computing A* heuristic functions for protein design and propose a variant of A* algorithm in which the search process can be performed on a single GPU in a massively parallel fashion. In addition, we make some efforts to address the memory exceeding problem in A* search. As a result, our enhancements can achieve a significant speedup of the A*-based protein design algorithm by four orders of magnitude on large-scale test data through pre-computation and parallelization, while still maintaining an acceptable memory overhead. We also show that our parallel A* search algorithm could be successfully combined with iMinDEE, a state-of-the-art DEE criterion, for rotamer pruning to further improve SCPR with the consideration of continuous side-chain flexibility. AVAILABILITY: Our software is available and distributed open-source under the GNU Lesser General License Version 2.1 (GNU, February 1999). The source code can be downloaded from http://www.cs.duke.edu/donaldlab/osprey.php or http://iiis.tsinghua.edu.cn/∼compbio/software.html.

Sub-features orthogonal decoupling: Detecting bone wall absence via a small number of abnormal examples for temporal CT images.

The absence of bone wall located in the jugular bulb and sigmoid sinus of the temporal bone is one of the important reasons for pulsatile tinnitus. Automatic and accurate detection of these abnormal singes in CT slices has important theoretical significance and clinical value. Due to the shortage of abnormal samples, imbalanced samples, small inter-class differences, and low interpretability, existing deep-learning methods are greatly challenged. In this paper, we proposed a sub-features orthogonal decoupling model, which can effectively disentangle the representation features into class-specific sub-features and class-independent sub-features in a latent space. The former contains the discriminative information, while, the latter preserves information for image reconstruction. In addition, the proposed method can generate image samples using category conversion by combining the different class-specific sub-features and the class-independent sub-features, achieving corresponding mapping between deep features and images of specific classes. The proposed model improves the interpretability of the deep model and provides image synthesis methods for downstream tasks. The effectiveness of the method was verified in the detection of bone wall absence in the temporal bone jugular bulb and sigmoid sinus.

Kindlin-3 mediates integrin αLß2 outside-in signaling, and it interacts with scaffold protein receptor for activated-C kinase 1 (RACK1).

Integrins are heterodimeric type I membrane cell adhesion molecules that are involved in many biological processes. Integrins are bidirectional signal transducers because their cytoplasmic tails are docking sites for cytoskeletal and signaling molecules. Kindlins are cytoplasmic molecules that mediate inside-out signaling and activation of the integrins. The three kindlin paralogs in humans are kindlin-1, -2, and -3. Each of these contains a 4.1-ezrin-radixin-moesin (FERM) domain and a pleckstrin homology domain. Kindlin-3 is expressed in platelets, hematopoietic cells, and endothelial cells. Here we show that kindlin-3 is involved in integrin αLß2 outside-in signaling. It also promotes micro-clustering of integrin αLß2. We provide evidence that kindlin-3 interacts with the receptor for activated-C kinase 1 (RACK1), a scaffold protein that folds into a seven-blade propeller. This interaction involves the pleckstrin homology domain of kindlin-3 and blades 5-7 of RACK1. Using the SKW3 human T lymphoma cells, we show that integrin αLß2 engagement by its ligand ICAM-1 promotes the association of kindlin-3 with RACK1. We also show that kindlin-3 co-localizes with RACK1 in polarized SKW3 cells and human T lymphoblasts. Our findings suggest that kindlin-3 plays an important role in integrin αLß2 outside-in signaling.

Serum vitamin D is associated with ultrasound-defined hepatic fibrosis.

BACKGROUND: Evidences from population-based investigations on the exact relationship between vitamin D and the severity of liver fibrosis remain debated and conflicting. Here, we aim to explore the relationship between serum vitamin D and ultrasound-defined advanced hepatic fibrosis in the US participants with nonalcoholic fatty liver disease (NAFLD). METHODS: In the retrospective study, individuals with intact information on interesting variables from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were included. NAFLD was diagnosed on the basis of controlling attenuation parameter (CAP) value≥ 274 dB/m without causes of other chronic hepatic diseases. We identified advanced fibrosis grades (F2) by liver stiffness measurement (LSM) score of ≥ 8.2 kPa in NAFLD patients. The impact of elevated serum vitamin D on the prevalence of hepatic fibrosis was assessed by multivariate logistic regression models on the basis of the NHANES recommended weights. RESULTS: The study involved 1624 subjects with NAFLD in total, and 305 (18.28 %, weighted%) of whom were diagnosed with advanced hepatic fibrosis according to the definition based on parameters obtained from vibration controlled transient elastography (VCTE). In the multivariate logistic regression analysis, serum vitamin D presented a negative relationship to hepatic fibrosis with lower odds in patients with hepatic steatosis after being adjusted for potential confounding factors (fully adjusted: OR=0.47, 95 % CI: 0.24-0.90, p = 0.034). Our subgroup analysis revealed that the inverse relationship was still existed in males (fully adjusted: OR = 0.34, 95 % CI: 0.17-0.70, p = 0.014), non-obese subjects (fully adjusted: OR = 0.20, 95 % CI: 0.04-0.89, p = 0.042) and participants below 60 years (fully adjusted: OR = 0.43, 95 % CI: 0.21-0.90, p = 0.033), whereas in models adjusted for the potential confounding factors, no statistically significant correlation was noted in females, obese subjects or subjects with age≥ 60 years. CONCLUSIONS: This large population-based investigation indicated that elevated serum vitamin D reduced the onset of advanced fibrosis diagnosed by ultrasound in males, non-obese subjects and younger participants with NAFLD.

ZC3H4 governs epithelial cell migration through ROCK/p-PYK2/p-MLC2 pathway in silica-induced pulmonary fibrosis.

BACKGROUND: Increased epithelial migration capacity is a key step accompanying epithelial-mesenchymal transition (EMT). Our lab has described that ZC3H4 mediated EMT in silicosis. Here, we aimed to explore the mechanisms of ZC3H4 by which to stimulate epithelial cell migration. METHODS: Silicon dioxide (SiO2)-induced pulmonary fibrosis (PF) animal models were administered by intratracheal instillation in C57BL/6 J mice. Pathological analysis and 2D migration assay were established to uncover the pulmonary fibrotic lesions and epithelial cell migration, respectively. Inhibitors targeting ROCK/p-PYK2/p-MLC2 and CRISPR/Cas9 plasmids targeting ZC3H4 were administrated to explore the signaling pathways. RESULTS: 1) SiO2 upregulated epithelial migration in pulmonary fibrotic lesions. 2) ZC3H4 modulated SiO2-induced epithelial migration. 3) ZC3H4 governed epithelial migration through ROCK/p-PYK2/p-MLC2 signaling pathway. CONCLUSIONS: ZC3H4 regulates epithelial migration through the ROCK/p-PYK2/p-MLC2 signaling pathway, providing the possibility that molecular drugs targeting ZC3H4-overexpression may exert effects on pulmonary fibrosis induced by silica.

Defining a cohort of anemia-activated cis elements reveals a mechanism promoting erythroid precursor function.

Acute anemia elicits broad transcriptional changes in erythroid progenitors and precursors. We previously discovered a cis-regulatory transcriptional enhancer at the sterile alpha motif domain-14 enhancer locus (S14E), defined by a CANNTG-spacer-AGATAA composite motif and occupied by GATA1 and TAL1 transcription factors, is required for survival in severe anemia. However, S14E is only 1 of dozens of anemia-activated genes containing similar motifs. In a mouse model of acute anemia, we identified populations of expanding erythroid precursors, which increased expression of genes that contain S14E-like cis elements. We reveal that several S14E-like cis elements provide important transcriptional control of newly identified anemia-inducing genes, including the Ssx-2 interacting protein (Ssx2ip). Ssx2ip expression was determined to play an important role in erythroid progenitor/precursor cell activities, cell cycle regulation, and cell proliferation. Over a weeklong course of acute anemia recovery, we observed that erythroid gene activation mediated by S14E-like cis elements occurs during a phase coincident with low hematocrit and high progenitor activities, with distinct transcriptional programs activated at earlier and later time points. Our results define a genome-wide mechanism in which S14E-like enhancers control transcriptional responses during erythroid regeneration. These findings provide a framework to understand anemia-specific transcriptional mechanisms, ineffective erythropoiesis, anemia recovery, and phenotypic variability within human populations.

Synchronizing Detection and Removal of Smoke in Endoscopic Images With Cyclic Consistency Adversarial Nets.

Smoke removal is an important and meaningful issue for endoscopic surgery, which can enhance the visual quality of endoscopic images. Because it is practically impossible to construct a large training dataset of pair-matched endoscopic images with/without smoke, the Generative Adversarial Nets (GANs) based models are usually used for endoscopic image desmoke. But they have difficulties in either locating the accurate smoke area, or recovering realistic internal organ or tissue details. In this paper, we propose a new approach, called Desmoke-CycleGAN, which combined detection, estimation, and removal of smoke together, to improve the CycleGAN model for endoscopic image smoke removal. In addition, both pixel-level and perceptual-level consistency loss have been incorporated in the proposed model, which helps the model to be more stable and efficient for recovering realistic details in endoscopic images. The experimental results have demonstrated that this method outperforms other state-of-the-art smoke removal approaches with unpaired real endoscopic images.

Labyrinth net: A robust segmentation method for inner ear labyrinth in CT images.

The inner ear labyrinth is a combined sensory organ of hearing and balance, which is surrounding the bony cavity located in the petrous temporal bone. The structure of the inner ear labyrinth plays an important role in otology research and clinic diagnosis of ear diseases. Automatic and accurate segmentation of the inner ear labyrinth is a foundation of computer-aided temporal bone quantitively measurements and diagnosis. The inner ear labyrinth is characterized by its complex morphology, small size, and high labeling cost, which brings challenges for deep learning-based automatic segmentation methods. In this paper, we propose a robust segmentation method for the labyrinth in temporal bone CT images via multi-model inconsistency. In the active-learning paradigm, we design an informative sample assessment strategy for screening informative unlabeled data. An observer network is introduced to confirm the confidence of segmented voxels based on the inconsistency to a backbone segmentation network. To further improve the efficiency of the sample screening, a maximum-connected probability map (MCP-Map) is introduced to eliminate the influence of outliers in the result of coarse segmentation. Experimental results show that our methods have the highest labeling efficiency and the lowest labeling cost compared with several existing active learning methods. With 40% labeled reduce, our method achieved 95.67% in Dice Similarity Coefficient (DSC), which is the state-of-the-art in the labyrinth segmentation.

Detecting Absence of Bone Wall in Jugular Bulb by Image Transformation Surrogate Tasks.

Anomaly detection in medical images is important in computer-aided diagnosis. It is a challenging task due to limited anomaly data, sample imbalance, and local differences between the normal and abnormal patterns. Abnormal manifestations in medical images have a definite clinical definition and descriptions, which can be introduced to improve the accuracy of detection rate. In this paper, we propose an anomaly detection method via image transformation surrogate tasks and apply it to detect the absence of bone wall in jugular bulb of temporal bone CT images. First, we design a pair of contrastive surrogate tasks, including an abnormal region completion and a normal background erasure, to decouple the similarity of the normal and abnormal examples. Then, image synthesis strategies for the surrogate tasks are designed, which alleviates the problem of limited abnormal data. Further, an abnormal scoring module is proposed, which includes MSE, SSIM, and local error intensity, to fuse the results of the surrogate tasks. We verify the effectiveness of our proposed method on the jugular bulb data set and experimental results show that the accuracy of our method is 0.995 and the AUC (Area Under the Curve) is 0.994.

Functional requirements for a Samd14-capping protein complex in stress erythropoiesis.

Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals-involving cooperation between stem cell factor (SCF)/Kit signaling and other signaling inputs-are required for the increased erythroid precursor activity in anemia. Our prior work revealed that the sterile alpha motif (SAM) domain 14 (Samd14) gene increases the regenerative capacity of the erythroid system in a mouse genetic model and promotes stress-dependent Kit signaling. However, the mechanism underlying Samd14's role in stress erythropoiesis is unknown. We identified a protein-protein interaction between Samd14 and the α- and ß-heterodimers of the F-actin capping protein (CP) complex. Knockdown of the CP ß subunit increased erythroid maturation in murine ex vivo cultures and decreased colony forming potential of stress erythroid precursors. In a genetic complementation assay for Samd14 activity, our results revealed that the Samd14-CP interaction is a determinant of erythroid precursor cell levels and function. Samd14-CP promotes SCF/Kit signaling in CD71med spleen erythroid precursors. Given the roles of Kit signaling in hematopoiesis and Samd14 in Kit pathway activation, this mechanism may have pathological implications in acute/chronic anemia.

Anemia is a condition in which the body has a shortage of healthy red blood cells to carry enough oxygen to support its organs. A range of factors are known to cause anemia, including traumatic blood loss, toxins or nutritional deficiency. An estimated one-third of all women of reproductive age are anemic, which can cause tiredness, weakness and shortness of breath. Severe anemia drives the release of hormones and growth factors, leading to a rapid regeneration of precursor red blood cells to replenish the supply in the blood. To understand how red blood cell regeneration is controlled, Ray et al. studied proteins involved in regenerating blood using mice in which anemia had been induced with chemicals. Previous research had shown that the protein Samd14 is produced at higher quantities in individuals with anemia, and is involved with the recovery of lost red blood cells. However, it is not known how the Samd14 protein plays a role in regenerating blood cells, or whether Samd14 interacts with other proteins required for red blood cell production. To shed light on these questions, mouse cells exposed to anemia conditions were used to see what proteins Samd14 binds to. Purifying Samd14 revealed that it interacts with the actin capping protein. This interaction relies on a specific region of Samd14 that is similar to regions in other proteins that bind capping proteins. Ray et al. found that the interaction between Samd14 and the actin capping protein increased the signals needed for the development and survival of new red blood cells. These results identify a signaling mechanism that, if disrupted, could cause anemia to develop. They lead to a better understanding of how our bodies recover from anemia, and potential avenues to treat this condition.

Association between polycyclic aromatic hydrocarbons exposure and bone turnover in adults.

BACKGROUND: Cigarette smoking is a risk factor of osteoporosis and bone fracture. Tobacco smoke contains several polycyclic aromatic hydrocarbons. Thus, we hypothesized that environmental polycyclic aromatic hydrocarbon exposure is associated with bone loss and fracture risk. The present study examined the association between polycyclic aromatic hydrocarbon exposure and bone turnover in the general adult population. METHODS: A total of 1408 eligible participants from the National Health and Nutrition Examination Survey (NHANES 2001-2006) were included in this cross-sectional analysis. The levels of urinary N-telopeptide and serum bone-specific alkaline phosphatase, which are biomarkers of bone resorption and formation, respectively, were assessed. Meanwhile, polycyclic aromatic hydrocarbon exposure was evaluated using the concentrations of urinary polycyclic aromatic hydrocarbon metabolites. The association between polycyclic aromatic hydrocarbon exposures and N-telopeptide, and bone-specific alkaline phosphatase levels was assessed using a multivariate linear regression model. RESULTS: All polycyclic aromatic hydrocarbon metabolites except 3-phenanthrene were significantly associated with increased N-telopeptide levels (P < 0.05) after adjustment of relevant covariables. However, no significant relationship was observed between polycyclic aromatic hydrocarbon metabolites and bone-specific alkaline phosphatase levels. This relationship remained significant after the participants were assessed according to sex (P < 0.05). Additionally, all polycyclic aromatic hydrocarbon metabolites showed a positive association with N-telopeptide levels in participants aged <60 years (P < 0.05). CONCLUSION: Polycyclic aromatic hydrocarbon exposure is associated with increased bone resorption among the general adult population in the United States. Further studies must assess the potential mechanisms associated with the adverse effects of polycyclic aromatic hydrocarbon exposure on bone loss.

Urinary biomarkers of polycyclic aromatic hydrocarbons and the association with hearing threshold shifts in the United States adults.

Polycyclic aromatic hydrocarbons (PAHs) are regarded as environmental pollutants that contribute to several adverse health outcomes. There is no research evidence to support a connection between PAH exposure and hearing loss. Our study aimed to determine the association between PAH exposure and hearing threshold shifts using the National Health and Nutrition Examination Survey (NHANES) dataset. A cross-sectional study was conducted among 1,071 US adults participating in the NHANES from 2001 to 2004. The association between PAH metabolites and the log-transformed hearing threshold was investigated using multivariate regression models, which included log-transformed, low-frequency and high-frequency thresholds. After additional pertinent adjustments, a positive correlation between PAH metabolite concentration and log-transformed hearing thresholds was observed. Individuals in the fourth quartile of PAH metabolite concentration had higher hearing thresholds compared with those in the first quartile of PAH metabolite concentration. Exposure to PAHs is related to hearing threshold shift at both low and high frequencies in the US adult population.

The relationship between lead and cadmium levels and functional dependence among elderly participants.

The adverse impacts of lead and cadmium exposure on health outcomes have been reported in the past. Few studies have been conducted on the relationship between lead and cadmium exposures and disability. We evaluated whether lead and cadmium exposures were associated with functional dependence including the total number of disabilities, activities of daily living (ADL), instrumental activities of daily living (IADL), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activities (GPA) in an elderly population. A total of 5513 eligible subjects were enrolled in the study from the National Health and Nutrition Examination Survey 2001-2006. Serum lead and cadmium exposure assessments were performed using atomic absorption spectrometry. Functional dependence was assessed by 19 structured questions. The relationships between lead and cadmium exposures and functional dependence were investigated using by multivariable linear regression models. Q2, Q3, and Q4 of lead exposure were significantly associated with the total number of disabilities, with ß coefficients of - 0.62 (95% CI - 0.99, - 0.24), - 0.64 (95% CI - 1.02, - 0.26), and - 0.81 (95% CI - 1.19, - 0.42), respectively. This relationship remained significant in males. Furthermore, we analyzed the relationships between lead and cadmium exposure quartiles and various functional dependence metrics, and we determined that lead content was significantly associated with decreased ADL, LEM, and GPA (p < 0.05) and cadmium content was inversely associated with ADL (p < 0.05). Our study demonstrated a strong relationship between exposure to lead and cadmium and functional dependence in an elderly population.

Examining the association between vestibular function and lower extremity circumference in an aged population.

AIM: To explore the association between vestibular dysfunction and specific anthropometric parameters. METHODS: The results from 2420 participants of the 1999-2004 National Health and Nutrition Examination Survey were included for the evaluation of vestibular dysfunction using the Romberg test of standing balance and anthropometric measurements, including waist circumference, thigh circumference, calf circumference (CC), waist-to-thigh ratio (WTR) and waist-to-calf ratio (WCR). Passing the balance test was defined as participants keeping their balance for 30 s while in the standing position with their eyes closed. Multivariable logistic regression models were the main statistical tools in the present study. RESULTS: The mean age of the participants was approximately 65 years, and half of the study participants were men. The full adjusted odds ratio of vestibular dysfunction for the CC, thigh circumference, WCR and WTR was 0.941 (95% confidence interval [CI], 0.894-0.992), 0.948 (95% CI 0.912-0.986), 1.856 (95% CI 1.087-3.170) and 2.516 (95% CI 1.235-5.126), respectively. Higher waist circumference along with lower thigh circumference and CC were observed in the participants in the higher WTR and WCR quartiles. Furthermore, a dose-response relationship between vestibular dysfunction and anthropometric ratios was detected. DISCUSSION: The present study showed that individuals with lower CC and thigh circumference or higher WCR and WTR exhibited higher odds of having vestibular dysfunction. Geriatr Gerontol Int 2019; 19: 622-627.

Helicobacter pylori infection increases risk of incident metabolic syndrome and diabetes: A cohort study.

Emerging studies have shed light on the association between Helicobacter pylori (HP) infection and cardiometabolic risk. However, there is no evidence to support a causal link for the relationship in the general population. Our aim was to determine whether HP infection is associated with the risks of incident type II diabetes mellitus (DM) in a population-based cohort consisting of adults from the general population. A total of 69235 adults enrolled in the study obtained health examinations at the Tri-Service General Hospital in Taiwan from 2010 to 2016. HP infection detection was performed by rapid urease tests (RUTs), and endoscopic examinations were used to diagnose gastroesophageal reflux disease (GERD), gastric ulcers (GUs) and duodenal ulcers (DUs). Cross-sectional and longitudinal analyses were performed to examine the association between HP infection and cardiometabolic diseases using logistic regression and Cox regression in a large population-based study. HP infection was significantly associated with the presence of metabolic syndrome (MetS) (OR = 1.26, 95%CI: 1.00-1.57) and DM (OR = 1.59, 95%CI: 1.17-2.17) only in male subjects, and abnormal endoscopic findings were also correlated with cardiometabolic diseases. Our findings demonstrated that participants with HP infection had an elevated risk of developing incident DM (HR = 1.54, 95%CI: 1.11-2.13). In addition, endoscopic findings of a DU (HR = 1.63, 95%CI: 1.02-2.63), rather than GERD or a GU, were also predictive of incident DM. In this cohort, HP infection was a statistically significant predictor of incident DM among male population.

The characterization and potential roles of bone morphogenetic protein 7 during spermatogenesis in Chinese mitten crab Eriocheir sinensis.

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-ß superfamily, have been implicated in various biological and physiological processes, especially in the gonad development. However, scarce studies were focused on the roles of BMPs in the reproductive system of crustaceans. In this study, the whole gene encoding BMP7 protein was cloned and characterized firstly in Chinese mitten crab Eriocheir sinensis. The bioinformatics analysis of the deduced amino acid sequence showed that Es-BMP7 was composed of prodomain/latency-associated peptide and the TGF-ß characteristic domain. The sequence conservation and phylogenetic analysis were also conducted. Quantitative real-time PCR was conducted indifferent tissues. The highest expression in testis indicated the potential role of BMP7 to male gonad development. Western blot results showed the different translational levels of BMP7 in different tissues. In-situ hybridization revealed that the expression of es-bmp7 signals presented in a bimodal manner: highest in spermatogonia, decreased in spermatocytes and stage I spermatids, disappeared in stage II spermatids, and showed up again in stage III spermatids and mature sperm. To further verify the potential roles during spermatogenesis, immunofluorescence was conducted and results showed the similar expression tendency with in situ hybridization. The protein signal was highest in the cytoplasm of spermatogonia, continued to decline in the cytoplasm of spermatocytes and the following stages, and weak signal was found in the mature sperm. Taken together, our results revealed that Es-BMP7 might play a part in testis development in Eriocheir sinensis, presumably by maintaining the self-renewal of spermatogonia and promoting the germ cell differentiation/meiotic mitosis, or facilitating the successful fertilization.

Body fat has stronger associations with bone mass density than body mass index in metabolically healthy obesity.

OBJECTIVE: The effect of obesity-induced metabolic abnormalities on bone mineral density (BMD) and osteoporosis are well established. However, the association between metabolically healthy obesity (MHO) and BMD remains unclear. Our aim was to investigate whether different obesity phenotypes in MHO were associated with BMD in a cross-sectional study. METHODS: All eligible adults receiving a health examination at the Tri-Service General Hospital from 2010 to 2016 were included. They were categorized based on body mass index (BMI) or percentage body fat (PBF). The associations between BMI or PBF and BMD were analyzed by adjusting for pertinent covariables. RESULTS: Males with normal weight and overweight and females with underweight and normal weight were associated with reduced BMD (ß = 0.221, 95%CI = -0.354, -0.088; ß = -0.155, 95%CI = -0.286, -0.023) (ß = -0.736, 95%CI = -1.043, 0.429; ß = -0.340, 95%CI = -0.567, -0.112), respectively. Females in Q1 had close to significant associations with reduced BMD (ß = -0.253, 95%CI = -0.465, -0.041). Normal weight, overweight, Q2, and Q3 had stronger prediction of low BMD with ORs of 0.402 (95%CI = 0.204-0.791), 0.539 (95%CI = 0.321-0.905), 0.694 (95%CI = 0.490-0.982), and 0.466 (95%CI = 0.342-0.636), respectively. The relationship remained significant in male population that PBF was associated with reduced BMD with ORs of 0.435 (95%CI = 0.203, 0.935), 0.494 (95%CI = 0.247, 0.991), 0.268 (95%CI = 0.120, 0.597) in Q1, Q2, Q3 respectively. CONCLUSION: Increased PBF had a significant association with low BMD in the MHO population. Obesity defined by PBF might be a useful indicator for low BMD. The association between body fat and bone health deserves further investigation regarding the potential pathophysiological mechanisms.