Novel Angiotensin-Converting Enzyme-Inhibitory Peptides Obtained from Trichiurus lepturus: Preparation, Identification and Potential Antihypertensive Mechanism.

Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of Trichiurus lepturus (ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC50 values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC50 = 262.98 µM), QGPIGPR (IC50 = 81.09 µM), and GPTGPAGP (IC50 = 168.11 µM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs.

HSP90AB1 is a host factor that promotes porcine deltacoronavirus replication.

Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus. It causes mortality in neonatal piglets and is of growing concern because of its broad host range, including humans. To date, the mechanism of PDCoV infection remains poorly understood. Here, based on a genome-wide CRISPR screen of PDCoV-infected cells, we found that HSP90AB1 (heat shock protein 90 alpha family class B1) promotes PDCoV infection. Knockdown or KO of HSP90AB1 in LLC-PK cells resulted in a significantly suppressed PDCoV infection. Infected cells treated with HSP90 inhibitors 17-AAG and VER-82576 also showed a significantly suppressed PDCoV infection, although KW-2478, which does not affect the ATPase activity of HSP90AB1, had no effect on PDCoV infection. We found that HSP90AB1 interacts with the N, NS7, and NSP10 proteins of PDCoV. We further evaluated the interaction between N and HSP90AB1 and found that the C-tail domain of the N protein is the HSP90AB1-interacting domain. Further studies showed that HSP90AB1 protects N protein from degradation via the proteasome pathway. In summary, our results reveal a key role for HSP90AB1 in the mechanism of PDCoV infection and contribute to provide new host targets for PDCoV antiviral research.

Semi-supervised point consistency network for retinal artery/vein classification.

Recent deep learning methods with convolutional neural networks (CNNs) have boosted advance prosperity of medical image analysis and expedited the automatic retinal artery/vein (A/V) classification. However, it is challenging for these CNN-based approaches in two aspects: (1) specific tubular structures and subtle variations in appearance, contrast, and geometry, which tend to be ignored in CNNs with network layer increasing; (2) limited well-labeled data for supervised segmentation of retinal vessels, which may hinder the effectiveness of deep learning methods. To address these issues, we propose a novel semi-supervised point consistency network (SPC-Net) for retinal A/V classification. SPC-Net consists of an A/V classification (AVC) module and a multi-class point consistency (MPC) module. The AVC module adopts an encoder-decoder segmentation network to generate the prediction probability map of A/V for supervised learning. The MPC module introduces point set representations to adaptively generate point set classification maps of the arteriovenous skeleton, which enjoys its prediction flexibility and consistency (i.e. point consistency) to effectively alleviate arteriovenous confusion. In addition, we propose a consistency regularization between the predicted A/V classification probability maps and point set representations maps for unlabeled data to explore the inherent segmentation perturbation of the point consistency, reducing the need for annotated data. We validate our method on two typical public datasets (DRIVE, HRF) and a private dataset (TR280) with different resolutions. Extensive qualitative and quantitative experimental results demonstrate the effectiveness of our proposed method for supervised and semi-supervised learning.

A Case of Fetal Familial Hemophagocytic Lymphohistiocytosis Type 5 caused by STXBP2 Gene Mutation.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is a rare hyper-inflammatory syndrome caused by mutations in STXBP2. Most cases present at 2 - 6 months of age, and FHL-5 is extremely rare in neonates. METHODS: Appropriate laboratory tests, abdominal ultrasonography and whole exome sequencing were carried out. Respiratory support, antibiotics, and transfusion of blood products were done. RESULTS: Laboratory tests revealed metabolic acidosis, thrombocytopenia, mild anemia, and low fibrinogen level. Blood culture, metagenomics, and TORCH screening were negative. Liver and spleen enlargements were confirmed by abdominal ultrasonography. Whole exome sequencing identified a homozygous mutation in STXBP2 c. 1432del G (p. V478Sfs*5). The heterozygous STXBP2 mutation was identified in the paternal grandfather, maternal grandfather, and parents. CONCLUSIONS: Here we report a case with a novel homozygous deletion in exon 16 of STXBP2, which caused the earliest reported case of FHL-5 in a neonate. Our results identify a new pathogenic variant for the early identification and clinical consultation of FHL-5.

Impact of Maternal Diabetes Mellitus on Neonatal Outcomes among Infants <32 Weeks of Gestation in China: A Multicenter Cohort Study.

OBJECTIVE: Our study aimed to determine the relationship between maternal diabetes mellitus (MDM) and mortality and major morbidities for very preterm infants, as well as the effects of insulin-treated MDM, in the Chinese population. STUDY DESIGN: This retrospective cohort study included all preterm infants born at 240/7 to 316/7 weeks of gestation and admitted to 57 tertiary neonatal intensive care units participating in the Chinese Neonatal Network in 2019. All infants were followed up until discharging from the hospitals. RESULTS: A total of 9,244 very preterm infants were enrolled, with 1,584 (17.1%) born to mothers with MDM. The rates of mortality or any major morbidity in the MDM and non-MDM groups were 45.9% (727/1,584) and 48.1% (3,682/7,660), respectively. After adjustment, the risk of mortality or any morbidity was not significantly increased in the MDM group (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 0.94-1.22) compared with the non-MDM group. Among MDM mothers with treatment data, 18.0% (256/1,420) were treated with insulin. Insulin-treated MDM was not independently associated with the risk of mortality or any morbidity (aOR, 1.01; 95% CI, 0.76-1.34) among very preterm infants, but it was associated with an elevated risk of severe retinopathy of prematurity (aOR, 2.39; 95% CI, 1.13-5.04). CONCLUSION: While the MDM diagnostic rate for mothers of very preterm infants was high in China, MDM was not associated with mortality or major morbidities for very preterm infants. KEY POINTS: · A total of 17% of very preterm infants in Chinese neonatal intensive care units were born to mothers with MDM.. · MDM was not related to mortality or major morbidities in very preterm infants.. · MDM treated by insulin was associated with severe retinopathy of prematurity..

Isolation of a Novel Anti-Diabetic α-Glucosidase Oligo-Peptide Inhibitor from Fermented Rice Bran.

At present, the incidence rate of diabetes is increasing gradually, and inhibiting α-glucosidase is one of the effective methods used to control blood sugar. This study identified new peptides from rice bran fermentation broth and evaluated their inhibitory activity and mechanism against α-glucosidase. Rice bran was fermented with Bacillus subtilis MK15 and the polypeptides of <3 kDa were isolated by ultrafiltration and chromatographic column, and were then subjected to LC-MS/MS mass spectrometry analysis. The results revealed that the oligopeptide GLLGY showed the greatest inhibitory activity in vitro. Docking studies with GLLGY on human α-glucosidase (PDB ID 5NN8) suggested a binding energy of −7.1 kcal/mol. GLLGY acts as a non-competitive inhibitor and forms five hydrogen bonds with Asp282, Ser523, Asp616, and His674 of α-glucosidase. Moreover, it retained its inhibitory activity even in a simulated digestion environment in vitro. The oligopeptide GLLGY could be developed into a potential anti-diabetic agent.

Novel angiotensin-converting enzyme and pancreatic lipase oligopeptide inhibitors from fermented rice bran.

This study determined the inhibitory activity of oligopeptides against angiotensin-converting enzyme (ACE) and pancreatic lipase through in vitro tests, molecular docking, and enzyme inhibition. The results showed that the IC50 of GLLGY, HWP, and VYGF for ACE inhibition was 1 mg/mL, and the IC50 of HWP for pancreatic lipase was 3.95 mg/mL. Molecular docking revealed that the binding energies between GLLGY, HWP, and VYGF and ACE were -9.0, -8.4, and -9.2 kcal/mol, respectively. The binding free energy between HWP and pancreatic lipase was -7.3 kcal/mol. GLLGY, HWP, and VYGF inhibited ACE compentitively. HWP inhibited pancreatic lipase through non-competition. in vitro simulated gastrointestinal digestion, the three oligopeptides still had inhibitory activity and low toxicity. The results revealed that the peptides GLLGY, HWP, and VYGF may be suitable candidates for further research on ACE inhibition, and HWP may be a suitable candidate for studying pancreatic lipase inhibition.

Multi-Scale Interactive Network With Artery/Vein Discriminator for Retinal Vessel Classification.

Automatic classification of retinal arteries and veins plays an important role in assisting clinicians to diagnosis cardiovascular and eye-related diseases. However, due to the high degree of anatomical variation across the population, and the presence of inconsistent labels by the subjective judgment of annotators in available training data, most of existing methods generally suffer from blood vessel discontinuity and arteriovenous confusion, the artery/vein (A/V) classification task still faces great challenges. In this work, we propose a multi-scale interactive network with A/V discriminator for retinal artery and vein recognition, which can reduce the arteriovenous confusion and alleviate the disturbance of noisy label. A multi-scale interaction (MI) module is designed in encoder for realizing the cross-space multi-scale features interaction of fundus images, effectively integrate high-level and low-level context information. In particular, we also design an ingenious A/V discriminator (AVD) that utilizes the independent and shared information between arteries and veins, and combine with topology loss, to further strengthen the learning ability of model to resolve the arteriovenous confusion. In addition, we adopt a sample re-weighting (SW) strategy to effectively alleviate the disturbance from data labeling errors. The proposed model is verified on three publicly available fundus image datasets (AV-DRIVE, HRF, LES-AV) and a private dataset. We achieve the accuracy of 97.47%, 96.91%, 97.79%, and 98.18% respectively on these four datasets. Extensive experimental results demonstrate that our method achieves competitive performance compared with state-of-the-art methods for A/V classification. To address the problem of training data scarcity, we publicly release 100 fundus images with A/V annotations to promote relevant research in the community.

Study of the inhibitory effect of STAT1 on PDCoV infection.

Porcine deltacoronavirus (PDCoV) is an enteropathogen found in many pig producing countries. It can cause acute diarrhea, vomiting, dehydration, and death in newborn piglets, seriously affecting the development of pig breeding industries. To date, our knowledge of the pathogenesis of PDCoV and its interactions with host cell factors remains incomplete. Using Co-IP coupled with LC/MS-MS, we identified 67 proteins that potentially interact with PDCoV in LLC-PK1 cells; five of the identified proteins were chosen for further evaluation (IMMT, STAT1, XPO5, PIK3AP1, and TMPRSS11E). Five LLC-PK1 cell lines, each with one of the genes of interest knocked down, were constructed using CRISPR/cas9. In these knockdown cells lines, only STAT1KD resulted in a significantly greater virus yield. Knockdown of the remaining four genes resulted, to varying degrees, in a lower virus yield that wild-type LLC-PK1 cells. The absence of STAT1 did not significantly affect the attachment of PDCoV to cells, but did result in increased viral internalization. Additionally, PDCoV infection stimulated expression of interferon stimulated genes (ISGs) downstream of STAT1 (IFIT1, IFIT2, RADS2, ISG15, MX1, and OAS1) while knockdown of STAT1 resulted in a greater than 80 % decrease in the expression of all six ISGs. Our findings show that STAT1 interacts with PDCoV, and plays a negative regulatory role in PDCoV infection.

Anti-Helicobacter pylori Activity of a Lactobacillus sp. PW-7 Exopolysaccharide.

Helicobacter pylori is a cause of gastric cancer. We extracted the exopolysaccharide (EPS) of Lactobacillus plajomi PW-7 for antibacterial activity versus H. pylori, elucidating its biological activity and structural characteristics. The minimum inhibitory concentration (MIC) of EPS against H. pylori was 50 mg/mL. Disruption of the cell membranes of pathogenic bacteria by EPS was indicated via the antibacterial mechanism test and confirmed through electron microscopy. EPS also has antioxidant capacity. The IC50 of EPS for 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anions, and hydroxyl radicals were 300 µg/mL, 180 µg/mL, and 10 mg/mL, respectively. The reducing power of EPS was 2 mg/mL, equivalent to 20 µg/mL of ascorbic acid. EPS is a heteropolysaccharide comprising six monosaccharides, with an approximate molecular weight of 2.33 × 104 Da. Xylose had a significant effect on H. pylori. EPS from L. plajomi PW-7 showed potential as an antibacterial compound and antioxidant, laying a foundation for the development of EPS-based foods.

Automatic Artery/Vein Classification Using a Vessel-Constraint Network for Multicenter Fundus Images.

Retinal blood vessel morphological abnormalities are generally associated with cardiovascular, cerebrovascular, and systemic diseases, automatic artery/vein (A/V) classification is particularly important for medical image analysis and clinical decision making. However, the current method still has some limitations in A/V classification, especially the blood vessel edge and end error problems caused by the single scale and the blurred boundary of the A/V. To alleviate these problems, in this work, we propose a vessel-constraint network (VC-Net) that utilizes the information of vessel distribution and edge to enhance A/V classification, which is a high-precision A/V classification model based on data fusion. Particularly, the VC-Net introduces a vessel-constraint (VC) module that combines local and global vessel information to generate a weight map to constrain the A/V features, which suppresses the background-prone features and enhances the edge and end features of blood vessels. In addition, the VC-Net employs a multiscale feature (MSF) module to extract blood vessel information with different scales to improve the feature extraction capability and robustness of the model. And the VC-Net can get vessel segmentation results simultaneously. The proposed method is tested on publicly available fundus image datasets with different scales, namely, DRIVE, LES, and HRF, and validated on two newly created multicenter datasets: Tongren and Kailuan. We achieve a balance accuracy of 0.9554 and F1 scores of 0.7616 and 0.7971 for the arteries and veins, respectively, on the DRIVE dataset. The experimental results prove that the proposed model achieves competitive performance in A/V classification and vessel segmentation tasks compared with state-of-the-art methods. Finally, we test the Kailuan dataset with other trained fusion datasets, the results also show good robustness. To promote research in this area, the Tongren dataset and source code will be made publicly available. The dataset and code will be made available at https://github.com/huawang123/VC-Net.

SA-Net: A scale-attention network for medical image segmentation.

Semantic segmentation of medical images provides an important cornerstone for subsequent tasks of image analysis and understanding. With rapid advancements in deep learning methods, conventional U-Net segmentation networks have been applied in many fields. Based on exploratory experiments, features at multiple scales have been found to be of great importance for the segmentation of medical images. In this paper, we propose a scale-attention deep learning network (SA-Net), which extracts features of different scales in a residual module and uses an attention module to enforce the scale-attention capability. SA-Net can better learn the multi-scale features and achieve more accurate segmentation for different medical image. In addition, this work validates the proposed method across multiple datasets. The experiment results show SA-Net achieves excellent performances in the applications of vessel detection in retinal images, lung segmentation, artery/vein(A/V) classification in retinal images and blastocyst segmentation. To facilitate SA-Net utilization by the scientific community, the code implementation will be made publicly available.

The growth performance and non-specific immunity of juvenile grass carp (Ctenopharyngodon idella) affected by dietary alginate oligosaccharide.

The effects of alginate oligosaccharides (AOs) on the growth performance and non-specific immunity of juvenile grass carp (Ctenopharyngodon idella) were investigated by performing a 60-day feeding trial. Four trial diets were formulated and supplemented with different doses of AOs (0, 100, 200 and 400 mg/kg). Triplicate groups of grass carp were fed with one of the diets twice daily. The grass carps fed with diets containing an appropriate dose of AOs for 60 days exhibited higher survival rates; body weight gains; specific growth rates; resistance to Aeromonas hydrophila; superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities; and serum total protein, lysozyme, alkaline phosphatase, complement C3, complement C4 and interleukin-10 expression levels and lower feed conversion ratios and malondialdehyde, alanine aminotransferase, aspartate aminotransferase, IL-1ß expression, IL-8 expression and tumor necrosis factor-α expression levels than the control group (p < 0.05). Based on the effects of AOs on growth performance and survival percent, the optimum dose of AOs was 200 mg/kg. Results indicate that AOs as a dietary supplement enhances the growth performance and non-specific immunity of grass carps and their resistance to diseases.

A novel protein chip for simultaneous detection of antibodies against four epidemic swine viruses in China.

BACKGROUND: At present, pig industry in China is faced with the complex situation of mixed infection caused by multiple pathogens. It is urgent to develop some new high-throughput molecular diagnosis assays to simultaneously detect pathogens or antibodies. Biochip array technology has made it possible to screen thousands of samples simultaneously; it has been twice named as one of the top 10 scientific and technological breakthroughs. Studies have reported encouraging results using protein biochips for detecting antibodies against avian infectious bronchitis virus and ruminant bluetongue virus, but the research of this technology for the diagnosis of swine diseases is still sparse. RESULTS: In this study, a novel protein chip was developed that can simultaneously detect the antibodies of four important swine viruses as follow, classical swine fever virus (CSFV), porcine parvovirus (PPV), Japanese encephalitis virus (JEV), and porcine reproductive and respiratory syndrome virus (PRRSV). Four prokaryotic expression plasmids pET-32a-E2 of CSFV, -VP2 of PPV, -EDIII of JEV, and -N of PRRSV were induced by IPTG (Isopropyl ß-D-1-Thiogalactopyranoside) and overexpressed in E.coli, respectively. The purified proteins were identified by Western blotting and then printed on epoxy-coated glass slides. The optimized parameters of this diagnostic chip showed that the spotting concentrations of E2、VP2、EDIII、N proteins were 0.2, 0.4, 0.4, and 0.4 mg/mL. The optimal primary and secondary antibody dilutions were 1:50 and 1: 600. Compared with the commercial ELISA (Enzyme-linked immunosorbent assay) kits, the positive and negative coincidence rates of this chip were 95.8% ~ 100 and 86.2% ~ 100%, as well as, no cross-reaction. CONCLUSION: This protein chip provided a fast, specific, and sensitive method for simultaneous detection of antibodies in clinical serum samples. Compared with traditional methods, this protein chip can monitor very small amount of serum.

Identification of a Novel Linear B-Cell Epitope on the Nucleocapsid Protein of Porcine Deltacoronavirus.

Porcine deltacoronavirus (PDCoV), first identified in 2012, is a swine enteropathogen now found in many countries. The nucleocapsid (N) protein, a core component of PDCoV, is essential for virus replication and is a significant candidate in the development of diagnostics for PDCoV. In this study, monoclonal antibodies (mAbs) were generated and tested for reactivity with three truncations of the full protein (N1, N2, N3) that contained partial overlaps; of the five monoclonals chosen tested, each reacted with only the N3 truncation. The antibody designated 4E88 had highest binding affinity with the N protein and was chosen for in-depth examination. The 4E88 epitope was located to amino acids 308-AKPKQQKKPKK-318 by testing the 4E88 monoclonal for reactivity with a series of N3 truncations, then the minimal epitope, 309-KPKQQKKPK-317 (designated EP-4E88), was pinpointed by testing the 4E88 monoclonal for reactivity with a series of synthetic peptides of this region. Homology analysis showed that the EP-4E88 sequence is highly conserved among PDCoV strains, and also shares high similarity with sparrow coronavirus (HKU17), Asian leopard cat coronavirus (ALCCoV), quail coronavirus (UAE-HKU30), and sparrow deltacoronavirus (SpDCoV). Of note, the PDCoV EP-4E88 sequence shared very low similarity (<22.2%) with other porcine coronaviruses (PEDV, TGEV, PRCV, SADS-CoV, PHEV), demonstrating that it is an epitope that can be used for distinguishing PDCoV and other porcine coronavirus. 3D structural analysis revealed that amino acids of EP-4E88 were in close proximity and may be exposed on the surface of the N protein.

Identification of the immunodominant neutralizing regions in the spike glycoprotein of porcine deltacoronavirus.

Porcine deltacoronavirus (PDCoV), is an emerging enteropathogenic coronavirus in pigs, that poses a novel threat to swine husbandry worldwide. Crucial to halting PDCoV transmission and infection is the development of effective therapies and vaccines. The spike (S) protein of coronavirus is the major target of host neutralizing antibodies, however the immunodominant neutralizing region in the S protein of PDCoV has not been defined. Here, three truncations of the PDCoV S protein were generated, the N-terminal domain of the S1 subunit (NTD, amino acids (aa) 50-286), the C-terminal domain of the S1 subunit (CTD, aa 278-616), and S2 subunit (aa 601-1087). The proteins were expressed using an E. coli expression system. Polyclonal antisera against the three recombinant proteins were produced in rabbits and mice. All three antisera were able to inhibit PDCoV infection in vitro, as determined by virus neutralization assay, fluorescent focus neutralization assay, and plaque-reduction neutralization. The CTD-specific antisera had the most potent PDCoV-neutralizing effect, indicating that the CTD region may contain the major neutralizing epitope(s) in the PDCoV S protein. Based on these findings, CTD may be a promising target for development of an effective vaccine against PDCoV infection in pigs.

Characterization and Pathogenicity of the Porcine Deltacoronavirus Isolated in Southwest China.

Porcine deltacoronavirus (PDCoV) is a newly emerging enteric pathogen in swine that causes diarrhea in neonatal piglets and creates an additional economic burden on porcine industries in Asia and North America. In this study, a PDCoV isolate, CHN-SC2015, was isolated from Sichuan Province in southwest China. The isolate was characterized by a cytopathic effect, immunofluorescence, and electron microscopy. CHN-SC2015 titers in LLC-PK cells ranged from 104.31 to 108.22 TCID50/mL during the first 30 passages. During serial passage, 11 nucleotide mutations occurred in the S gene, resulting in nine amino acid changes. A whole genome sequencing analysis demonstrated that CHN-SC2015 shares 97.5%-99.1% identity with 59 reference strains in GenBank. Furthermore, CHN-SC2015 contained 6-nt deletion and 9-nt insertion in the ORF1ab gene, 3-nt deletion in the S gene and 11-nt deletion in its 3'UTR compared with other reference strains available in GenBank. A phylogenetic analysis showed that CHN-SC2015 is more closely related to other PDCoV strains in China than to the strains from Southeast Asia, USA, Japan, and South Korea, indicating the diversity of genetic relationships and regional and epidemic characteristics among these strains. A recombination analysis indicated that CHN-SC2015 experienced recombination events between SHJS/SL/2016 and TT-1115. In vivo infection demonstrated that CHN-SC2015 is highly pathogenic to sucking piglets, causing diarrhea, vomiting, dehydration, and death. Virus was shed daily in the feces of infected piglets and upon necropsy, was found distributed in the gastrointestinal tract and in multiple organs. CHN-SC2015 is the first systematically characterized strain from southwest China hitherto reported. Our results enrich the body of information on the epidemiology, pathogenicity and molecular evolution associated with PDCoV.

Levodopa is effective in the treatment of three Chinese Tyrosine hydroxylase (TH) deficiency children.

Tyrosine hydroxylase (TH) deficiency is a rare autosomal recessive inborn error of dopamine transmission, which the deficient gene is at the chromosome 11, also called'Segawa Syndrome'. TH converts tyrosine into L-DOPA, which is the direct precursor of catecholamine biosynthesis. TH deficiency causes a neurological disease with primary extrapyramidal signs and a variable response to L-DOPA. We report three patients in China who were diagnosed with Tyrosine hydroxylase (TH) deficiency by genetic testing and clinical manifestations. After L-DOPA treatment, their condition had sustained improvement.

LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis.

OBJECTIVE: Sepsis is a whole-body inflammation disease after severe trauma, burn injury, infection and major surgeries, accompanied by multiple organs failure. We sought to investigate the potential mechanism of Aquaporin 1 (AQP1), miRNA-874, and lncRNA H19 in lipopolysaccharide (LPS) sepsis and the anti-inflammatory responses related to sepsis myocardial dysfunction. MATERIAL AND METHODS: Serum from peripheral blood samples of sepsis patients and in vivo mice model were collected for AQP1, H19, and miR-874 expression. In vitro model in cardiomyocytes was established using LPS. H19 and miR-874 expressions were interfered in LPS induced mice and cardiomyocytes to explore the association between them and its effect on anti-inflammatory responses. RESULTS: H19 and AQP1 decreased and accompanied with elevated miR-874 expression in sepsis samples, in vivo mice model and in vitro cells. There was negative relationship between expression of H19 and miR-874, and a positive correlation between H19 and AQP1 expression. However, H19 overexpression transfection significantly reversed LPS induced dysregulation in expression of miR-874 and AQP1, secretion of anti-inflammatory cytokines, and myocardial dysfunction in vivo and in vitro. CONCLUSION: We determined that H19 acted as AQP1 ceRNA in regulating miR-874. H19 acted as AQP1 ceRNA in regulating miR-874 and restoring LPS dysregulated inflammatory responses and myocardial dysfunction. H19 expression might be used as a potential therapeutic target for LPS induced sepsis and myocardial dysfunction.

A case of Pitt-hopkins Syndrome with de novo mutation in TCF4: Clinical features and treatment for epilepsy.

Pitt-Hopkins syndrome (PTHS), belonging to the group of 18q-syndromes, is a rare genetic disorder caused by mutations in TCF4. PTHS is characterized by distinctive facial appearance, intermittent hyperventilation, intellectual disability and developmental delay. Although patients with PTHS generally have various systemic symptoms, most of them with a TCF4 mutation manifest the central nervous system (CNS) disorders. We described the first Chinese case with Pitt-Hopkins syndrome based on clinical presentations and genetic findings. In addition to the typical features of PTHS, the girl also had paroxysms of tachypnea followed by cyanosis and recurrent seizures. Comprehensive medical examinations were performed including metabolic screening, hepatic and renal function evaluation, abdominal and cardiac ultrasounds. The presence of epileptic discharges in electroencephalography and abnormal brain magnetic resonance imaging were found. High-throughput sequencing was used to detect genetic mutations associated with CNS disorders. Sanger sequencing was used to confirm the mutations in the patient. The c.2182C＞T (p.Arg728Ter) mutation was a de novo nonsense mutation at exon 18 in the TCF4 gene of the patient. In conclusion, we have identified a de novo nonsense mutation of TCF4 carried by a Chinese girl with PTHS. The patient underwent anti-epileptic therapy (sodium valproate, levetiracetam, clonazepam), resulting in a reduction of the seizures.