CEMIG: prediction of the cis-regulatory motif using the de Bruijn graph from ATAC-seq.

Sequence motif discovery algorithms enhance the identification of novel deoxyribonucleic acid sequences with pivotal biological significance, especially transcription factor (TF)-binding motifs. The advent of assay for transposase-accessible chromatin using sequencing (ATAC-seq) has broadened the toolkit for motif characterization. Nonetheless, prevailing computational approaches have focused on delineating TF-binding footprints, with motif discovery receiving less attention. Herein, we present Cis rEgulatory Motif Influence using de Bruijn Graph (CEMIG), an algorithm leveraging de Bruijn and Hamming distance graph paradigms to predict and map motif sites. Assessment on 129 ATAC-seq datasets from the Cistrome Data Browser demonstrates CEMIG's exceptional performance, surpassing three established methodologies on four evaluative metrics. CEMIG accurately identifies both cell-type-specific and common TF motifs within GM12878 and K562 cell lines, demonstrating its comparative genomic capabilities in the identification of evolutionary conservation and cell-type specificity. In-depth transcriptional and functional genomic studies have validated the functional relevance of CEMIG-identified motifs across various cell types. CEMIG is available at https://github.com/OSU-BMBL/CEMIG, developed in C++ to ensure cross-platform compatibility with Linux, macOS and Windows operating systems.

A dual-energy CT reconstruction method based on anchor network from dual quarter scans.

Compared with conventional single-energy computed tomography (CT), dual-energy CT (DECT) provides better material differentiation but most DECT imaging systems require dual full-angle projection data at different X-ray spectra. Relaxing the requirement of data acquisition is an attractive research to promote the applications of DECT in wide range areas and reduce the radiation dose as low as reasonably achievable. In this work, we design a novel DECT imaging scheme with dual quarter scans and propose an efficient method to reconstruct the desired DECT images from the dual limited-angle projection data. We first study the characteristics of limited-angle artifacts under dual quarter scans scheme, and find that the negative and positive artifacts of DECT images are complementarily distributed in image domain because the corresponding X-rays of high- and low-energy scans are symmetric. Inspired by this finding, a fusion CT image is generated by integrating the limited-angle DECT images of dual quarter scans. This strategy enhances the true image information and suppresses the limited-angle artifacts, thereby restoring the image edges and inner structures. Utilizing the capability of neural network in the modeling of nonlinear problem, a novel Anchor network with single-entry double-out architecture is designed in this work to yield the desired DECT images from the generated fusion CT image. Experimental results on the simulated and real data verify the effectiveness of the proposed method. This work enables DECT on imaging configurations with half-scan and largely reduces scanning angles and radiation doses.

F. prausnitzii-derived extracellular vesicles attenuate experimental colitis by regulating intestinal homeostasis in mice.

BACKGROUND: Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice. RESULTS: Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1ß (IL-1ß), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor ß (TGF-ß) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). CONCLUSION: Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile.

Association of multimorbidity patterns with motoric cognitive risk syndrome among older adults: Evidence from a China longitudinal study.

OBJECTIVES: Motoric cognitive risk syndrome (MCR), a pre-dementia syndrome, is characterized by slow gait and subjective cognitive complaints among older adults. This study assessed the relationship between multimorbidity, its patterns, and MCR. METHODS: Data for this study were obtained from three waves (2011, 2013, and 2015) of the China Health and Retirement Longitudinal Study. Participants who were aged 60 years and older and had complete data at baseline as well as complete data about MCR at follow-up were selected. Patients without MCR at baseline were selected for further analyses. Longitudinal associations between multimorbidity, its patterns, and MCR were examined using a Cox proportional hazards model. Multimorbidity patterns were classified using latent class analysis. RESULTS: A total of 4923 respondents were included at baseline, 43.47% of whom had multimorbidity. Additionally, the prevalence of MCR at baseline was 12.61%. After adjusting for covariates, multimorbidity was positively associated with MCR (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 1.06-1.68). A higher number of multimorbidity was also significantly associated with an increased risk of developing MCR (HR = 1.10, 95% CI = 1.02-1.19). Three multimorbidity patterns were selected: relatively healthy pattern, respiratory pattern, and cardiovascular pattern. Older adults with the cardiovascular pattern were 1.57 times more likely to develop MCR than those with the relatively healthy pattern (HR = 1.57, 95% CI = 1.16-2.13). There was no significant difference between the relatively healthy pattern and the respiratory pattern (HR = 1.31, 95% CI = 0.91-1.92). CONCLUSIONS: MCR is highly prevalent among older Chinese adults. MCR may be exacerbated by multimorbidity. For older adults with multimorbidity (especially cardiovascular multimorbidity), attention should be paid to MCR to achieve early detection, diagnosis, and treatment.

Embryonic epigenetic reprogramming by a pioneer transcription factor in plants.

Epigenetic modifications, including chromatin modifications and DNA methylation, have a central role in the regulation of gene expression in plants and animals. The transmission of epigenetic marks is crucial for certain genes to retain cell lineage-specific expression patterns and maintain cell fate. However, the marks that have accumulated at regulatory loci during growth and development or in response to environmental stimuli need to be deleted in gametes or embryos, particularly in organisms such as plants that do not set aside a germ line, to ensure the proper development of offspring. In Arabidopsis thaliana, prolonged exposure to cold temperatures (winter cold), in a process known as vernalization, triggers the mitotically stable epigenetic silencing of the potent floral repressor FLOWERING LOCUS C (FLC), and renders plants competent to flower in the spring; however, this silencing is reset during each generation. Here we show that the seed-specific transcription factor LEAFY COTYLEDON1 (LEC1) promotes the initial establishment of an active chromatin state at FLC and activates its expression de novo in the pro-embryo, thus reversing the silenced state inherited from gametes. This active chromatin state is passed on from the pro-embryo to post-embryonic life, and leads to transmission of the embryonic memory of FLC activation to post-embryonic stages. Our findings reveal a mechanism for the reprogramming of embryonic chromatin states in plants, and provide insights into the epigenetic memory of embryonic active gene expression in post-embryonic phases, through which an embryonic factor acts to 'control' post-embryonic development processes that are distinct from embryogenesis in plants.

Generation and application of a convolutional neural networks algorithm in evaluating stool consistency in diapers.

AIM: The aim of the study was to develop a deep convolutional neural networks (CNNs) algorithm for automated assessment of stool consistency from diaper photographs and test its performance under real-world conditions. METHODS: Diaper photographs were enrolled via a mobile phone application. The stool consistency was assessed independently according to the Brussels Infant and Toddler Stool Scale (BITSS) by paediatricians. These images were randomised into a training data set and a test data set. After training and testing, the new algorithm was used under real-world conditions by parents. RESULTS: There was an overall agreement of 92.9% between paediatricians and the CNN-generated algorithm. Post hoc classification into the validated 4 categories of the BITSS yielded an agreement of 95.4%. Spearman correlation analysis across the ranking of 7 BITSS photographs and validated 4 categories showed a significant correlation of rho = 0.93 (95% CI, 0.92, 0.94; p < 0.001) and rho = 0.92 (95% CI, 0.90, 0.93; p < 0.001), respectively. The real-world application yielded further insights into changes in stool consistency between age categories and mode of feeding. CONCLUSION: The new CNN-based algorithm is able to reliably identify stool consistency from diaper photographs and may support the communication between parents and paediatricians.

Projection domain processing for low-dose CT reconstruction based on subspace identification.

PURPOSE: Low-dose computed tomography (LDCT) has promising potential for dose reduction in medical applications, while suffering from low image quality caused by noise. Therefore, it is in urgent need for developing new algorithms to obtain high-quality images for LDCT. METHODS: This study tries to exploit the sparse and low-rank properties of images and proposes a new algorithm based on subspace identification. The collection of transmission data is sparsely represented by singular value decomposition and the eigen-images are then denoised by block-matching frames. Then, the projection is regularized by the correlation information under the frame of prior image compressed sensing (PICCS). With the application of a typical analytical algorithm on the processed projection, the target images are obtained. Both numerical simulations and real data verifications are carried out to test the proposed algorithm. The numerical simulations data is obtained based on real clinical scanning three-dimensional data and the real data is obtained by scanning experimental head phantom. RESULTS: In simulation experiment, using new algorithm boots the means of PSNR and SSIM by 1 dB and 0.05, respectively, compared with BM3D under the Gaussian noise with variance 0.04. Meanwhile, on the real data, the proposed algorithm exhibits superiority over compared algorithms in terms of noise suppression, detail preservation and computational overhead. The means of PSNR and SSIM are improved by 1.84 dB and 0.1, respectively, compared with BM3D under the Gaussian noise with variance 0.04. CONCLUSION: This study demonstrates the feasibility and advantages of a new algorithm based on subspace identification for LDCT. It exploits the similarity among three-dimensional data to improve the image quality in a concise way and shows a promising potential on future clinical diagnosis.

Pediococcus pentosaceus CECT 8330 protects DSS-induced colitis and regulates the intestinal microbiota and immune responses in mice.

BACKGROUND: Compelling evidences demonstrated that gut microbiota dysbiosis plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Therapies for targeting the microbiota may provide alternative options for the treatment of IBD, such as probiotics. Here, we aimed to investigate the protective effect of a probiotic strain, Pediococcus pentosaceus (P. pentosaceus) CECT 8330, on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were administered phosphate-buffered saline (PBS) or P. pentosaceus CECT 8330 (5 × 108 CFU/day) once daily by gavage for 5 days prior to or 2 days after colitis induction by DSS. Weight, fecal conditions, colon length and histopathological changes were examined. ELISA and flow cytometry were applied to determine the cytokines and regulatory T cells (Treg) ratio. Western blot was used to examine the tight junction proteins (TJP) in colonic tissues. Fecal short-chain fatty acids (SCFAs) levels and microbiota composition were analyzed by targeted metabolomics and 16S rRNA gene sequencing, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of orthologous groups of proteins (COG) pathway analysis were used to predict the microbial functional profiles. RESULTS: P. pentosaceus CECT 8330 treatment protected DSS-induced colitis in mice as evidenced by reducing the weight loss, disease activity index (DAI) score, histological damage, and colon length shortening. P. pentosaceus CECT 8330 decreased the serum levels of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6), and increased level of IL-10 in DSS treated mice. P. pentosaceus CECT 8330 upregulated the expression of ZO-1, Occludin and the ratio of Treg cells in colon tissue. P. pentosaceus CECT 8330 increased the fecal SCFAs level and relative abundances of several protective bacteria genera, including norank_f_Muribaculaceae, Lactobacillus, Bifidobacterium, and Dubosiella. Furthermore, the increased abundances of bacteria genera were positively correlated with IL-10 and SCFAs levels, and negatively associated with IL-6, IL-1ß, and TNF-α, respectively. The KEGG and COG pathway analysis revealed that P. pentosaceus CECT 8330 could partially recover the metabolic pathways altered by DSS. CONCLUSIONS: P. pentosaceus CECT 8330 administration protects the DSS-induced colitis and modulates the gut microbial composition and function, immunological profiles, and the gut barrier function. Therefore, P. pentosaceus CECT 8330 may serve as a promising probiotic to ameliorate intestinal inflammation.

HISTONE DEACETYLASE 6 suppresses salicylic acid biosynthesis to repress autoimmunity.

Salicylic acid (SA) plays an important role for plant immunity, especially resistance against biotrophic pathogens. SA quickly accumulates after pathogen attack to activate downstream immunity events and is normally associated with a tradeoff in plant growth. Therefore, the SA level in plants has to be strictly controlled when pathogens are absent, but how this occurs is not well understood. Previously we found that in Arabidopsis (Arabidopsis thaliana), HISTONE DEACETYLASE 6 (HDA6), a negative regulator of gene expression, plays an essential role in plant immunity since its mutation allele shining 5 (shi5) exhibits autoimmune phenotypes. Here we report that this role is mainly through suppression of SA biosynthesis: first, the autoimmune phenotypes and higher resistance to Pst DC3000 of shi5 mutants depended on SA; second, SA significantly accumulated in shi5 mutants; third, HDA6 repressed SA biosynthesis by directly controlling the expression of CALMODULIN BINDING PROTEIN 60g (CBP60g) and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1). HDA6 bound to the chromatin of CBP60g and SARD1 promoter regions, and histone H3 acetylation was highly enriched within these regions. Furthermore, the transcriptome of shi5 mutants mimicked that of plants treated with exogenous SA or attacked by pathogens. All these data suggest that HDA6 is vital for plants in finely controlling the SA level to regulate plant immunity.

Potential roles for pattern molecule of PAMP-triggered immunity in improving crop cold tolerance.

KEY MESSAGE: The application of flagellin 22 (flg22), the most widely studied PAMP, enhance crop cold tolerance. ICE1-CBF pathway and SA signaling is involved in the alleviation of cold injury by flg22 treatment. Pathogen infection cross-activates cold response and increase cold tolerance of host plants. However, it is not possible to use the infection to increase cold tolerance of field plants. Here flagellin 22 (flg22), the most widely studied PAMP (pathogen-associated molecular patterns), was used to mimic the pathogen infection to cross-activate cold response. Flg22 treatment alleviated the injury caused by freezing in Arabidopsis, oilseed and tobacco. In Arabidopsis, flg22 activated the expression of immunity and cold-related genes. Moreover, the flg22 induced alleviation of cold injury was lost in NahG transgenic line (SA-deficient), sid2-2 and npr1-1 mutant plants, and flg22-induced expression of cold tolerance-related genes, which indicating that salicylic acid signaling pathway is required for the alleviation of cold injury by flg22 treatment. In short flg22 application can be used to enhance cold tolerance in field via a salicylic acid-depended pathway.

One case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome featuring an incomplete and mild phenotype.

BACKGROUND: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year. CASE PRESENTATION: Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient's clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients' cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid. CONCLUSIONS: We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.

Total variation combining nonlocal means filtration for image reconstruction in X-ray computed tomography.

BACKGROUND: Image reconstruction for realistic medical images under incomplete observation is still one of the core tasks for computed tomography (CT). However, the stair-case artifacts of Total variation (TV) based ones have restricted the usage of the reconstructed images. OBJECTIVE: This work aims to propose and test an accurate and efficient algorithm to improve reconstruction quality under the idea of synergy between local and nonlocal regularizations. METHODS: The total variation combining the nonlocal means filtration is proposed and the alternating direction method of multipliers is utilized to develop an efficient algorithm. The first order approximation of linear expansion at intermediate point is applied to overcome the computation of the huge CT system matrix. RESULTS: The proposed method improves root mean squared error by 25.6% compared to the recent block-matching sparsity regularization (BMSR) on simulation dataset of 19 views. The structure similarities of image of the new method is higher than 0.95, while that of BMSR is about 0.92. Moreover, on real rabbit dataset of 20 views, the peak signal-to-noise ratio (PSNR) of the new method is 36.84, while using other methods PSNR are lower than 35.81. CONCLUSIONS: The proposed method shows advantages on noise suppression and detail preservations over the competing algorithms used in CT image reconstruction.

Musculoskeletal actinomycosis in children: a case report.

BACKGROUND: Actinomycosis is a rare infectious disease caused by Actinomyces, especially in children. Here, we present a case of musculoskeletal actinomycosis in a 5-year-old girl from China. CASE PRESENTATION: A 5-year-old girl presented with recurrent episodes of fever, pain, erythema, swelling, and festering sores on the right lower extremity, and pus was discharged from a sinus in the right foot. Magnetic resonance imaging (MRI) suggested subcutaneous soft tissue infection and osteomyelitis of the right crus. A bacterial culture of pus extracted from a festering sore on the right popliteal fossa detected the growth of Actinomycetes europaeus. The patient was cured with 7 weeks of treatment with intravenous ampicillin-sulbactam, followed by 6 weeks of treatment with oral amoxicillin-clavulanate with surgical debridement and drainage. There were no symptoms of recurrence during the 15-month period of follow-up. CONCLUSIONS: Pediatric actinomycosis is a rare and challenging infectious disease. Early accurate diagnosis and optimal surgical debridement are important for the management of pediatric actinomycosis.

Dual residual convolutional neural network (DRCNN) for low-dose CT imaging.

The excessive radiation doses in the application of computed tomography (CT) technology pose a threat to the health of patients. However, applying a low radiation dose in CT can result in severe artifacts and noise in the captured images, thus affecting the diagnosis. Therefore, in this study, we investigate a dual residual convolution neural network (DRCNN) for low-dose CT (LDCT) imaging, whereby the CT images are reconstructed directly from the sinogram by integrating analytical domain transformations, thus reducing the loss of projection information. With this new framework, feature extraction is performed simultaneously on both the sinogram-domain sub-net and the image-domain sub-net, which utilize the residual shortcut networks and play a complementary role in suppressing the projection noise and reducing image error. This new DRCNN approach helps not only decrease the sinogram noise but also preserve significant structural information. The experimental results of simulated and real projection data demonstrate that our DRCNN achieve superior performance over other state-of-art methods in terms of visual inspection and quantitative metrics. For example, comparing with RED-CNN and DP-ResNet, the value of PSNR using our DRCNN is improved by nearly 3 dB and 1 dB, respectively.

An effective sinogram inpainting for complementary limited-angle dual-energy computed tomography imaging using generative adversarial networks.

Dual-energy computed tomography (DECT) provides more anatomical and functional information for image diagnosis. Presently, the popular DECT imaging systems need to scan at least full angle (i.e., 360°). In this study, we propose a DECT using complementary limited-angle scan (DECT-CL) technology to reduce the radiation dose and compress the spatial distribution of the imaging system. The dual-energy total scan is 180°, where the low- and high-energy scan range is the first 90° and last 90°, respectively. We describe this dual limited-angle problem as a complementary limited-angle problem, which is challenging to obtain high-quality images using traditional reconstruction algorithms. Furthermore, a complementary-sinogram-inpainting generative adversarial networks (CSI-GAN) with a sinogram loss is proposed to inpainting sinogram to suppress the singularity of truncated sinogram. The sinogram loss focuses on the data distribution of the generated sinogram while approaching the target sinogram. We use the simultaneous algebraic reconstruction technique namely, a total variable (SART-TV) algorithms for image reconstruction. Then, taking reconstructed CT images of pleural and cranial cavity slices as examples, we evaluate the performance of our method and numerically compare different methods based on root mean square error (RMSE), peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). Compared with traditional algorithms, the proposed network shows advantages in numerical terms. Compared with Patch-GAN, the proposed network can also reduce the RMSE of the reconstruction results by an average of 40% and increase the PSNR by an average of 26%. In conclusion, both qualitative and quantitative comparison and analysis demonstrate that our proposed method achieves a good artifact suppression effect and can suitably solve the complementary limited-angle problem.

Pst DC3000 infection alleviates subsequent freezing and heat injury to host plants via a salicylic acid-dependent pathway in Arabidopsis.

Abiotic stresses greatly affect the immunity of plants. However, it is unknown whether pathogen infection affects abiotic stress tolerance of host plants. Here, the effect of defense response on cold and heat tolerance of host plants was investigated in Pst DC3000-infected Arabidopsis plants, and it was found that the pathogen-induced defense response could alleviate the injury caused by subsequent cold and heat stress (38°C). Transcriptomic sequencing plus RT-qPCR analyses showed that some abiotic stress genes are up-regulated in transcription by pathogen infection, including cold signaling components ICE1, CBF1, and CBF3, and some heat signaling components HSFs and HSPs. Moreover, the pathogen-induced alleviation of cold and heat injury was lost in NahG transgenic line (SA-deficient), sid2-2 and npr1-1 mutant plants, and pathogen-induced expression of cold and heat tolerance-related genes such as CBFs and HSPs, respectively, was lost or compromised in these plants, indicating that salicylic acid signaling pathway is required for the alleviation of cold and heat injury by pathogen infection. In short, our current work showed that in fighting against pathogens, host plants also enhance their cold and heat tolerance via a salicylic acid-dependent pathway.

A novel hippocampus metabolite signature in diabetes mellitus rat model of diabetic encephalopathy.

Diabetic encephalopathy (DE) is one of the chronic complications of diabetes. Even then, the molecular mechanism underlying DE remains unexplored. In this study, we have made an attempt to investigate the metabolic changes associated with the streptozocin (STZ)-induced cognitive dysfunction in the hippocampus of the rat model, a classical rodent model for DE, with the help of Gas Chromatography-Mass Spectrometry-based method. The STZ injections led to the rise of mean blood glucose levels in the diabetes mellitus (DM) group of rats as compared to the control (CON) group of rats throughout the experiment. However, we did not find any significant difference between the blood glucose levels of the DM & the CON groups of rats before the STZ injection. The results indicated a behavioral and morphological cognitive dysfunction in the DM groups of rats. The metabolomic investigation of these DE rats demonstrated a lower level of N-acetylaspartate and dihydroxyacetone phosphate accompanied by a higher level of homocysteine and glutamate as against the CON group of rats. The outcome of this study may unravel the underlying pathophysiological mechanism of DE. Also, the metabolomic data from this study may provide a platform for the development of DE biomarkers.

Ménétrier's disease in childhood: a case report from China.

BACKGROUND: Ménétrier's disease (MD) is a protein-losing gastropathy characterized by gastric hypertrophy, foveolar hyperplasia and hypoalbuminemia. MD is uncommon in childhood with nonspecific clinical symptoms, and the exact cause of pediatric MD is still unclear. CASE PRESENTATION: Here, we reported a 4 year and 10-month boy presenting with MD from China. The patient was suffered with vomiting, abdominal pain, hypoproteinemia and edema. Laboratory tests showed that the boy was infected with Clostridium difficile (CD). Gastrointestinal endoscopy revealed giant gastric folds, and histological gastric biopsies showed foveolar hyperplasia with glandular atrophy, infiltration of eosinophils in the lamina propria of the patient. Finally, the boy was recovered after supportive therapy with intravenous albumin and CD eradication. CONCLUSION: For the nonspecific clinical symptoms of MD, gastrointestinal endoscopic evaluations with gastric tissue biopsies are required to establish the diagnosis of MD in children with unexplained hypoalbuminemia.

The NUCLEAR FACTOR-CONSTANS complex antagonizes Polycomb repression to de-repress FLOWERING LOCUS T expression in response to inductive long days in Arabidopsis.

Many plants sense the seasonal cues, day length or photoperiod changes, to align the timing of the developmental transition to flowering with changing seasons for reproductive success. Inductive day lengths through the photoperiod pathway induce the expression of FLOWERING LOCUS T (FT) or FT relatives that encode a major mobile florigen to promote flowering. In Arabidopsis thaliana, under inductive long days the photoperiod pathway output CONSTANS (CO) accumulates toward the end of the day, and associates with the B and C subunits of Nuclear Factor Y (NF-Y) to form the NF-CO complex that acts to promote FT expression near dusk, whereas Polycomb group (PcG) proteins function to silence FT expression. How NF-CO acts to antagonize the function of PcG proteins to regulate FT expression remains unclear. Here, we show that the NF-CO complex bound to the proximal FT promoter, through chromatin looping, acts in concert with an NF-Y complex bound to a distal enhancer to reduce the levels of PcG proteins, including both Polycomb repressive complex 1 (PRC1) and PRC2 at the FT promoter, leading to a relieving of Polycomb silencing and thus FT de-repression near dusk. Thus, our study provides molecular insights on how the 'active' photoperiod pathway and the 'repressive' Polycomb silencing system interact to control temporal FT expression, conferring the long-day induction of flowering in Arabidopsis.

Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Several types of PFIC were defined based on different genetic aetiologies in last decades. CASE PRESENTATION: Here, we report a Chinese young child diagnosed as PFIC with variants in tight junction protein 2 (TJP2). The patient was affected by a long history of jaundice, pruritus, and failure to thrive. Highly elevated level of serum total bile acid (TBA) and normal levels of gamma-glutamyltransferase (GGT) were observed at hospitalization. The patient's clinical symptoms could be alleviated by administration of ursodeoxycholic acid. Genetic testing by next generation sequencing (NGS) found novel compound heterozygote mutations c.2448 + 1G > C/c.2639delC (p.T880Sfs*12) in TJP2, which were inherited from her mother and father, respectively. Both mutations were predicted to abolish TJP2 protein translation, and neither has previously been identified. CONCLUSION: We report a Chinese female PFIC child with novel compound heterozygous mutations of TJP2. Genetic testing by NGS is valuable in the clinical diagnosis of hereditary liver disease.