hSef potentiates EGF-mediated MAPK signaling through affecting EGFR trafficking and degradation

Sef (similar expression to fgf genes) was identified as an effective antagonist of fibroblast growth factor (FGF) in vertebrates. Previous reports have demonstrated that Sef interacts with FGF receptors (FGFRs) and inhibits FGF signaling, however, its role in regulating epidermal growth factor receptor (EGFR) signaling remains unclear. In this report, we found that hSef localizes to the plasma membrane (PM) and is subjected to rapid internalization and well localizes in early/recycling endosomes while poorly in late endosomes/lysosomes. We observed that hSef interacts and functionally colocalizes with EGFR in early endosomes in response to EGF stimulation. Importantly, we demonstrated that overexpression of hSef attenuates EGFR degradation and potentiates EGF-mediated mitogen-activated protein kinase (MAPK) signaling by interfering EGFR trafficking. Finally, our data showed that, with overexpression of hSef, elevated levels of Erk phosphorylation and differentiation of rat pheochromocytoma (PC12) cells occur in response to EGF stimulation. Taken together, these data suggest that hSef plays a positive role in the EGFR-mediated MAPK signaling pathway. This report, for the first time, reveals opposite roles for Sef in EGF and FGF signalings

Case report: Two cases of Poirier-Bienvenu neurodevelopmental syndrome and review of literature

The Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare disease caused by mutations in the CSNK2B gene, which is characterized by intellectual disability and early-onset epilepsy. Mosaicism has not been previously reported in CSNK2B gene. POBINDS is autosomal dominant and almost all reported cases were de novo variants. Here, we report two patients were diagnosed with POBINDS. Using Whole Exome Sequencing (WES), we detected two novel CSNK2B variants in the two unrelated individuals: c.634_635del (p.Lys212AspfsTer33) and c.142C > T (p.Gln48Ter) respectively. Both of them showed mild developmental delay with early-onset and clustered seizures. The patient with c.634_635del(p.Lys212AspfsTer33) variant was mutant mosaicism, and the proportion of alleles in peripheral blood DNA was 28%. Further, the literature of patients with a de novo mutation of the CSNK2B gene was reviewed, particularly seizure semiology and genotype-phenotype correlations

Ultrasound characteristics of the cervical vagus nerve in patients with type 2 diabetes and diabetic peripheral neuropathy

Introduction: Diabetic peripheral neuropathy (DPN) and autonomic neuropathy are commonly coexistent in patients with type 2 diabetes mellitus (T2DM). Current assessment tools for diabetic neuropathy remain complicated and limited. We aimed to investigate the sonographic changes of the cervical vagus nerve in DPN patients with T2DM. Material and methods: Patients with T2DM were divided into a DPN group (DPN, n = 44) and non-DPN controls (NDPN, n = 43) based on electromyogram results. Another 43 healthy controls (CON) were included. High-frequency ultrasound (HFU) of the vagus nerve was performed in all participants. Results: Compared with controls, the honeycomb structure of the vagus nerve in patients with T2DM decreased, p < 0.001. The DPN group had higher cross-sectional area (CSA) of the right vagus nerve than the NDPN group (1.60 ± 0.52 vs. 2.00 ± 0.57 mm2, p =0.001). Logistic regression showed that right vagus nerve CSA was a risk factor of DPN (odds ratio [OR] = 3.924, p = 0.002). Right vagus nerve CSA was positively correlated with diabetes duration (p = 0.003), and negatively correlated with the motor conduction velocity (MCV) of the ulnar, median, and common peroneal nerves (p < 0.001 for all), as well as the sensor conduction velocity (SCV) of the ulnar and median nerve (both p < 0.005). Conclusion: HFU shows thickening of the cervical vagus nerve in patients with DPN, which is a potential diagnostic feature of diabetic neuropathy

Recent advances in ocular graft-versus-host disease

Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals’ quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment

Two novel variations in LRP2 cause Donnai-Barrow syndrome in a Chinese family with severe early-onset high myopia

Donnai-Barrow syndrome (DBS) is a rare autosomal recessive disorder caused by mutation in the low density lipoprotein receptor-related protein 2 gene (LRP2). Defects in this protein may lead to clinical multiple organ malformations by affecting the development of organs such as the nervous system, eyes, ears, and kidneys. Although some variations on LRP2 have been found to be associated with DBS, early diagnosis and prevention of patients with atypical DBS remains a challenge for many physicians because of their clinical heterogeneity. The objective of this study is to explore the association between the clinical presentation and the genotype of a DBS patient who was initially diagnosed with early-onset high myopia (eoHM) from a healthy Chinese family. To this end, we tested the patient of this family via whole exome sequencing and further verified the results among other family members by Sanger sequencing. Comprehensive ophthalmic tests as well as other systemic examinations were also performed on participants with various genotypes. Genetic assessment revealed that two novel variations in LRP2, a de novo missense variation (c.9032G>A; p.Arg3011Lys) and a novel splicing variation (c.2909-2A>T) inherited from the father, were both carried by the proband in this family, and they are strongly associated with the typical clinical features of DBS patients. Therefore, in this paper we are the first to report two novel compound heterozygous variations in LPR2 causing DBS. Our study extends the genotypic spectrums for LPR2-DBS and better assists physicians in predicting, diagnosing, and conducting gene therapy for DBS

Equilibrium and Kinetic Studies on Biosorption of Common Edible Macrofungi to Pb (II): a Comparative Study

In this work, we studied the natural bioaccumulation and biosorption of Pb(II) in several common edible macrofungi. They include the following species: Lentinus edodes, Pleurotus eryngii, Flammulina velutipes, Hypsizygus marmoreus, and Agrocybe cylindracea. The present analysis of Pb(II) revealed distinct capabilities of metal accumulation among individual species. Moreover, the natural concentrations of lead did not reach a health risk level when cultivated in uncontaminated soil. In the biosorption experiment by edible macrofungi, we found that the equilibrium data of living sporocarp (P. eryngii and H. marmoreus) and the homogenate of L. edodes and F. velutipes fit the Freundlich model well. Other data samples exhibited a better fit to the Langmuir model. The edible macrofungi showed a higher lead removal capacity than other biosorbents. Furthermore, the pseudo-second-order kinetics model exhibited the best fit to the the biosorption processes. The effectiveness of edible macrofungi as biosorbent for Pb(II) was confirmed.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

N-Terminal Polypeptide of Annexin A2 Decreases Infection of Mycoplasma hyorhinis to Gastric Cancer Cells.

Mycoplasma infection in human and its contamination in cell cultures are worldwide problems. The drugs currently available for preventing or treating mycoplasma infection suffer from low sensitivity, strong resistance and high toxicity. Our previous work showed that Mycoplasma hyorhinis (M. hyorhinis) infection was mediated by the interaction between p37 of M. hyorhinis and Annexin A2 (ANXA2) of host cells, however the translational value of this mechanism was unknown. Herein, we synthesized the N-terminal of ANXA2 polypeptide (A2PP) and found that A2PP could decrease the infection of M. hyorhinis to gastric cancer cells and block M. hyorhinis infection-induced cell migration. Furthermore, we found that A2PP could reduce M. hyorhinis contamination of passage cells. Moreover, compared with the commercial antibiotics commonly used in cell culture to prevent M. hyorhinis infection, A2PP demonstrated a more effectiveness but a low toxicity on cell growth. Thus, our study for the first time revealed A2PP's potential for the treatment and prevention of M. hyorhinis infection

Different Responses of Bacterial and Archaeal Communities in River Sediments to Water Diversion and Seasonal Changes

In recent years, different responses of archaea and bacteria to environmental changes have attracted increasing scientific interest. In the mid-latitude region, Fen River receives water transferred from the Yellow River, electrical conductivity (EC), concentrations of Cl− and Na+ in water, total phosphorus (TP), and Olsen phosphorus (OP) in sediments were significantly affected by water transfer. Meanwhile, temperature and oxidation-reduction potential (ORP) of water showed significant seasonal variations. Based on 16S rRNA high-throughput sequencing technology, the composition of bacteria and archaea in sediments was determined in winter and summer, respectively. Results showed that the dominance of bacterial core flora decreased and that of archaeal core flora increased after water diversion. The abundance and diversity of bacterial communities in river sediments were more sensitive to anthropogenic and naturally induced environmental changes than that of archaeal communities. Bacterial communities showed greater resistance than archaeal communities under long-term external disturbances, such as seasonal changes, because of rich species composition and complex community structure. Archaea were more stable than bacteria, especially under short-term drastic environmental disturbances, such as water transfer, due to their insensitivity to environmental changes. These results have important implications for understanding the responses of bacterial and archaeal communities to environmental changes in river ecosystems affected by water diversion

A2PP suppresses migration of gastric cancer cell induced by <i>M</i>. <i>hyorhinis</i> infection.

<p>(A) Migration of 10⁵ CCU/ml of <i>M</i>. <i>hyorhinis</i>-infected AGS and BGC823 cells treated with indicated peptides for 24 hr. (B) Summary of migration assays (n = 3). Mean ± SD from 3 independent experiments with triplicate samples. ***, P<0.001.</p

A2PP reduces <i>M</i>. <i>hyorhinis</i> infection.

<p>Cell ELISA analysis of p37 (OD 490 nm) of p37 protein in AGS and BGC823 cells infected with 10⁵ CCU (color changing units)/ml of <i>M</i>. <i>hyorhinis</i> and treated with A2PP or ConP for 24 hr. <i>M</i>. <i>hy</i>, <i>M</i>. <i>hyorhinis</i>. Mean ± SD from 3 experiments with triplicate for each sample. (B) Quantitative PCR (qPCR) analysis of <i>p37</i> in AGS and BGC823 cells infected and treated as in (A). Mean ± SD from 3 experiments with triplicate for each sample. (C) Western blotting of p37, p-EGFR, EGFR, p-ANXA2 and ANXA2 from AGS and BGC823 cells treated as in (A). (D) Quantification of p37 protein levels of in (C). Levels of p37 were normalized to those of GAPDH. Mean ± SD from 3 independent experiments. (E) Quantification of p-EGFR and p-ANXA2 levels in (C). Levels of p-EGFR or p-ANXA2 were normalized to those of EGFR or ANXA2. Mean ± SD from 3 independent experiments. **, P < 0.01; **, P < 0.001; n.s, no significance.</p