[Corrigendum] Bax inhibitor­1 suppresses early brain injury following experimental subarachnoid hemorrhage in rats.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 6 on p. 2898, the 'SAH' and 'SAH+NC' data panels contained an apparently overlapping section of data, such that these data appeared to have been derived from the same original source, even though they were intended to show the results from differently performed experiments. The authors have examined their original data, and realize that the 'SAH+NC' data panel had inadvertently been selected incorrectly for this figure. In addition, in response to a further query from the reader, the authors wished to point out that the standard deviations in their study were statistically analysed using GraphPad Prism software version 5.0a. The revised version of Fig. 6, now showing the correct data for the 'SAH+NC' experiment, is shown on the next page. The authors can confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 42: 2891­2902, 2018; DOI: 10.3892/ijmm.2018.3858].

Insm1 regulates mTEC development and immune tolerance.

The expression of self-antigens in medullary thymic epithelial cells (mTECs) is essential for the establishment of immune tolerance, but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly understood. Here, we show that Insm1, a zinc finger protein with known functions in neuroendocrine and neuronal cells, is broadly coexpressed with an autoimmune regulator (Aire) in mTECs. Insm1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic cells. Mutation of Insm1 in mice downregulated Aire expression, dysregulated the gene expression program of mTECs, and altered mTEC subpopulations and the expression of tissue-restricted antigens. Consistent with these findings, loss of Insm1 resulted in autoimmune responses in multiple peripheral tissues. We found that Insm1 regulates gene expression in mTECs by binding to chromatin. Interestingly, the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer regions. Together, our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.

lhCLIP reveals the in vivo RNA-RNA interactions recognized by hnRNPK.

RNA-RNA interactions play a crucial role in regulating gene expression and various biological processes, but identifying these interactions on a transcriptomic scale remains a challenge. To address this, we have developed a new biochemical technique called pCp-biotin labelled RNA hybrid and ultraviolet crosslinking and immunoprecipitation (lhCLIP) that enables the transcriptome-wide identification of intra- and intermolecular RNA-RNA interactions mediated by a specific RNA-binding protein (RBP). Using lhCLIP, we have uncovered a diverse landscape of intermolecular RNA interactions recognized by hnRNPK in human cells, involving all major classes of noncoding RNAs (ncRNAs) and mRNA. Notably, hnRNPK selectively binds with snRNA U4, U11, and U12, and shapes the secondary structure of these snRNAs, which may impact RNA splicing. Our study demonstrates the potential of lhCLIP as a user-friendly and widely applicable method for discovering RNA-RNA interactions mediated by a particular protein of interest and provides a valuable tool for further investigating the role of RBPs in gene expression and biological processes.

Low-dose LPS alleviates early brain injury after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.

BACKGROUND: Low-dose lipopolysaccharide (LPS) protects against early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanism underlying the neuroprotective roles of low-dose LPS remain largely undefined. METHODS: A SAH mice model was established and the pathological changes of brain were evaluated by wet-dry weight method, HE and Nissl staining, and blood-brain barrier (BBB) permeability assay. Cell apoptosis and inflammation were monitored by TUNEL, flow cytometry and ELISA assays. qRT-PCR, immunofluorescence and Western blot were used to detect the expression of microglial polarization-related or oxidative stress-associated markers. Bioinformatics analysis, luciferase and ChIP assays were employed to detect the direct association between FOXO1 and IL-10 promoter. The ubiquitination of FOXO1 in the in vitro SAH model was detected by co-IP. RESULTS: Low-dose LPS alleviated SAH-induced neurological dysfunction, brain edema, BBB disruption, damage in the hippocampus, neuronal apoptosis and inflammation via modulating microglial M1/M2 polarization by IL-10/IL-10R1 signaling. Mechanistic studies showed that FOXO1 acted as a transcriptional activator of IL-10. USP19 mediated the deubiquitination of FOXO1 to activate IL-10/IL-10R1 signaling, thereby regulating microglial M1/M2 polarization. Functional experiments revealed that low-dose LPS upregulated USP19 to modulate microglial M1/M2 polarization via FOXO1/IL-10/IL-10R1 signaling in SAH mice. CONCLUSION: Low-dose LPS protected against EBI after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.

Comprehensive Genomic Analysis Reveals Extensive Diversity of Type I and Type IV Secretion Systems in Klebsiella pneumoniae.

The diversity and distribution of secretion systems in Klebsiella pneumoniae are unclear. In this study, the six common secretion systems (T1SS-T6SS) were comprehensively investigated in the genomes of 952 K. pneumoniae strains. T1SS, T2SS, type T subtype of T4SS, T5SS, and subtype T6SSi of T6SS were found. The findings indicated fewer types of secretion systems in K. pneumoniae than reported in Enterobacteriaceae, such as Escherichia coli. One conserved T2SS, one conserved T5SS, and two conserved T6SS were detected in more than 90% of the strains. In contrast, the strains displayed extensive diversity of T1SS and T4SS. Notably, T1SS and T4SS were enriched in the hypervirulent and classical multidrug resistance pathotypes of K. pneumoniae, respectively. The results expand the epidemiological knowledge of the virulence and transmissibility of pathogenic K. pneumoniae and contribute to identify the potential strains for safe applications.

A genome-scale metabolic model of the effect of dissolved oxygen on 1,3-propanediol fermentation by Klebsiella pneumoniae.

Although 1,3-propanediol (1,3-PD) is usually considered an anaerobic fermentation product from glycerol by Klebsiella pneumoniae, microaerobic conditions proved to be more conducive to 1,3-PD production. In this study, a genome-scale metabolic model (GSMM) specific to K. pneumoniae KG2, a high 1.3-PD producer, was constructed. The iZY1242 model contains 2090 reactions, 1242 genes and 1433 metabolites. The model was not only able to accurately characterise cell growth, but also accurately simulate the fed-batch 1,3-PD fermentation process. Flux balance analyses by iZY1242 was performed to dissect the mechanism of stimulated 1,3-PD production under microaerobic conditions, and the maximum yield of 1,3-PD on glycerol was 0.83 mol/mol under optimal microaerobic conditions. Combined with experimental data, the iZY1242 model is a useful tool for establishing the best conditions for microaeration fermentation to produce 1,3-PD from glycerol in K. pneumoniae.

Analysis of Risk Factors for Epilepsy after Combined Re-Vascularization in Adult Patients with Moyamoya Disease.

Background and Objective: Re-vascularization is an effective treatment for moyamoya disease (MMD) patients, including direct re-vascularization, indirect re-vascularization and combined re-vascularization, in which combined re-vascularization is particularly widely used. At present, there are few reports on the analysis of epilepsy after combined re-vascularization surgery. To analysis the risk factors of epilepsy in adult MMD patients after combined re-vascularization. Material and Methods: Patients with MMD who underwent combined re-vascularization in the Department of Neurosurgery of the First People's Hospital of Yunnan Province from January 2015 to June 2020 were included. Their pre-operative and post-operative complication-related indicators were collected. Finally, logistic regression was used to analyze the clinical risk factors of epilepsy in MMD patients after operation. Results: The incidence of epilepsy after combined re-vascularization was 15.5%. Univariate analysis showed that pre-operative ischemic or hemorrhagic stroke, pre-operative epilepsy, pre-operative history of diabetes, the location of the bypass recipient artery (frontal or temporal lobe), post-operative new cerebral infarction, hyper-perfusion syndrome, and post-operative intra-cranial hemorrhage were the clinical risk factors of epilepsy in MMD patients (all P < 0.05). Multi-variate logistic regression analysis showed that pre-operative epilepsy, the location of the bypass recipient artery, new cerebral infarction, hyper-perfusion syndrome, and post-operative intra-cranial hemorrhage (all P < 0.05) were independent risk factors for post-operative epilepsy in MMD patients. Conclusions: Pre-operative epilepsy, the location of the bypass recipient artery, new cerebral infarction, hyper-perfusion syndrome, and intra-cranial hemorrhage may have a causal relationship with epilepsy in adult MMD patients. It is suggested that some risk factors could be intervened to reduce the incidence of post-operative epilepsy in MMD patients.

Clinical value of the systemic immune-inflammation index in moyamoya disease.

Background: Moyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. The underlying pathophysiological mechanism of moyamoya disease remains to be elucidated, but recent studies have increasingly highlighted that abnormal immune response may be a potential trigger for MMD. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are inflammatory markers that can reflect the immune-inflammation state of the disease. Objective: The purpose of this study was to investigate SII, NLR, and PLR in patients with moyamoya disease. Methods: A total of 154 patients with moyamoya disease (MMD group) and 321 age- and sex-matched healthy subjects (control group) were included in this retrospective case-control study. Complete blood count parameters were assayed to calculate the SII, NLR, and PLR values. Results: The SII, NLR, and PLR values in the moyamoya disease group were significantly higher than those in the control group [754 ± 499 vs. 411 ± 205 (P < 0.001), 2.83 ± 1.98 vs. 1.81 ± 0.72 (P < 0.001), and 152 ± 64 vs. 120 ± 42 (P < 0.001), respectively]. The SII in the medium-moyamoya vessels of moyamoya disease was higher than that in the high-moyamoya vessels and low-moyamoya vessels (P = 0.005). Using the receiver operating characteristic (ROC) curve analysis to predict MMD, the highest area under the curve (AUC) was determined for SII (0.76 for SII, 0.69 for NLR, and 0.66 for PLR). Conclusion: Based on the results of this study, patients with moyamoya disease admitted for inpatient care due to acute or chronic stroke have significantly higher SII, NLR, and PLR when compared to blood samples drawn from completely healthy controls in a non-emergent outpatient setting. While the findings may suggest that inflammation plays a role in moyamoya disease, further studies are warranted to corroborate such an association. In the middle stage of moyamoya disease, there may be a more intense imbalance of immune inflammation. Further studies are needed to determine whether the SII index contributes to the diagnosis or serves as a potential marker of an inflammatory response in patients with moyamoya disease.

The SNAG Domain of Insm1 Regulates Pancreatic Endocrine Cell Differentiation and Represses ß- to δ-Cell Transdifferentiation.

The allocation and specification of pancreatic endocrine lineages are tightly regulated by transcription factors. Disturbances in differentiation of these lineages contribute to the development of various metabolic diseases, including diabetes. The insulinoma-associated protein 1 (Insm1), which encodes a protein containing one SNAG domain and five zinc fingers, plays essential roles in pancreatic endocrine cell differentiation and in mature ß-cell function. In the current study, we compared the differentiation of pancreatic endocrine cells between Insm1 null and Insm1 SNAG domain mutants (Insm1delSNAG) to explore the specific function of the SNAG domain of Insm1. We show that the δ-cell number is increased in Insm1delSNAG but not in Insm1 null mutants as compared with the control mice. We also show a less severe reduction of the ß-cell number in Insm1delSNAG as that in Insm1 null mutants. In addition, similar deficits are observed in α-, PP, and ε-cells in Insm1delSNAG and Insm1 null mutants. We further identified that the increased δ-cell number is due to ß- to δ-cell transdifferentiation. Mechanistically, the SNAG domain of Insm1 interacts with Lsd1, the demethylase of H3K4me1/2. Mutation in the SNAG domain of Insm1 results in impaired recruitment of Lsd1 and increased H3K4me1/2 levels at hematopoietically expressed homeobox (Hhex) loci that are bound by Insm1, thereby promoting the transcriptional activity of the δ-cell-specific gene Hhex Our study has identified a novel function of the SNAG domain of Insm1 in the regulation of pancreatic endocrine cell differentiation, particularly in the repression of ß- to δ-cell transdifferentiation.

Pulmonary angiosarcoma presenting with diffuse alveolar hemorrhage: a case report.

This study aimed to analyze the diagnosis and treatment of one case of pulmonary angiosarcoma (PPA) retrospectively. The main manifestation of this female patient was cough, hemoptysis and dyspnea. Computed tomography (CT) of the chest revealed multiple small nodules and ground-glass patches in both lungs suggesting of diffuse alveolar hemorrhage (DAH). Laboratory examination revealed decreased hemoglobin and platelet counting, normal coagulation function. Results of rheumatic markers testing including antinuclear antibody (ANA), anti-extractable nuclear antigen antibody (ENA), vasculitis marker, and antiphospholipid antibody were negative. Tumor markers were negative. Sputum smear, sputum culture, and alveolar lavage fluid culture showed negative results. The bone marrow smear was essentially normal. The patient received methylprednisolone pulse therapy (250 mg daily × 5 days) and immunoglobin (20 d daily × 7 days) treatment, but her hemoptysis persisted. Bilateral pleural effusion drainage found a large amount of bloody effusion, but cytology of the pleural fluid showed negative results. The clinical symptoms, laboratory results, imaging findings, and pathological features of the patient were summarized, and problems in diagnosis and treatment were discussed. A thoracoscopic lung biopsy was performed and the diagnosis of PPA was confirmed by pathology and immunohistochemistry (IHC) staining. This case suggested that the possibility of PPA should be considered in patients with DAH, but with negative findings in routine examinations, lung biopsy is usually required.

Two Bariatric Surgical Procedures Differentially Alter the Intestinal Microbiota in Obesity Patients.

AIMS: To explore the intestinal microbiota composition affected by the two most widely used procedures of bariatric surgery, laparoscopic sleeve gastrectomy (LSG) and laparoscopic roux-en-Y gastric bypass (LRYGB), in Chinese obesity patients. METHODS: Stool samples were collected from the obese patients before (n = 87) and with follow-up after the surgery (n = 53). After DNA extraction, 16S rDNA (V3 + V4 regions) sequencing was completed on Illumina HiSeq 2500 sequencing platform. The samples were analyzed base on four groups, pre-LSG (n = 54), pre-LRYGB (n = 33), post-LSG (n = 33), and post-LRYGB (n = 20). The linear mixed models were used to analyze the alteration of intestinal microbiota before and after the surgeries of LSG or LRYGB. Student's t test and χ2 test were used for analysis of independent groups; Metastats analysis was used to compare the relative abundance of bacteria, and Pearson correlation and Spearman correlation analysis were used to test the correlation between indicated groups. RESULTS: 87 patients were included and 53 (60.92%) of them completed the follow-up (9.60 ± 3.92 months). Body mass index (BMI) decreased from 37.84 ± 6.16 kg/m2 to 26.22 ± 4.33 kg/m2 after LSG and from 45.75 ± 14.26 kg/m2 to 33.15 ± 10.99 kg/m2 after LRYGB. The relative abundance of 5 phyla and 42 genera were altered after the surgery in the cohort. Although no alteration of Firmicutes was observed at phylum level, 54.76% of the altered genera belong to phylum Firmicutes. Both LSG and LRYGB procedures increased the richness and evenness of intestinal microbiota in obese patients after the surgery. Particularly, 33 genera altered after LSG and 19 genera altered after LRYGB, in which 11 genera were common alterations in both procedures. CONCLUSION: Both LSG and LRYGB altered the composition of intestinal microbiota in Chinese obesity patients, and particularly increased the richness and evenness of microbiota. Genera belonging to phylum Firmicutes were the most altered bacteria by bariatric surgery. The procedure of LSG resulted in much more pronounced alteration of the intestinal microbiota abundance than that observed in LRYGB. While different genera were altered after LSG and LRYGB procedures, 10 genera were the common altered genera in both procedures. Bacteria altered after LSG and LRYGB were functionally associated with BMI, and with relieving of the metabolic syndromes.

Renal Subcapsular Transplantation of 2'-Deoxyguanosine-Treated Murine Embryonic Thymus in Nude Mice.

The thymus is an important central immune organ, which plays an essential role in the development and differentiation of T cells. Thymus transplantation is an important method for investigating thymic epithelial cell function and T cells maturation in vivo. Here we will describe the experimental methods used within our laboratory to transplant 2'-deoxyguanosine (to deplete donor's lymphocytes) treated embryonic thymus into the renal capsule of an athymic nude mouse. This method is both simple and efficient and does not require special skills or devices. The results obtained via this simple method showed that transplanted thymus can effectively support the recipient's T cells production. Additionally, several key points with regards to the protocol will be further elucidated.

Iron(iii)-catalyzed radical α,ß-aminophosphinoylation of styrenes with diphenylphosphine oxides and anilines.

A Fe-catalyzed highly regioselective α,ß-difunctionalization of vinylarenes with diphenylphosphine oxides and anilines is disclosed, in which α,ß-aminophosphinoylation is efficiently and conveniently constructed under mild conditions with good functional compatibility and a broad substrate scope. The control experiments have revealed a radical reaction pathway.

Haploinsufficiency of Insm1 Impairs Postnatal Baseline ß-Cell Mass.

Baseline ß-cell mass is established during the early postnatal period when ß-cells expand. In this study, we show that heterozygous ablation of Insm1 decreases baseline ß-cell mass and subsequently impairs glucose tolerance. When exposed to a high-fat diet or on an ob/ob background, glucose intolerance was more severe in Insm1+/lacZ mice compared with Insm1+/+ mice, although no further decrease in the ß-cell mass was detected. In islets of early postnatal Insm1+/lacZ mice, the cell cycle was prolonged in ß-cells due to downregulation of the cell cycle gene Ccnd1 Although Insm1 had a low affinity for the Ccnd1 promoter compared with other binding sites, binding affinity was strongly dependent on Insm1 levels. We observed dramatically decreased binding of Insm1 to the Ccnd1 promoter after downregulation of Insm1 expression. Furthermore, downregulation of Ccnd1 resulted in a prolonged cell cycle, and overexpression of Ccnd1 rescued cell cycle abnormalities observed in Insm1-deficient ß-cells. We conclude that decreases in Insm1 interfere with ß-cell specification during the early postnatal period and impair glucose homeostasis during metabolic stress in adults. Insm1 levels are therefore a factor that can influence the development of diabetes.

Bax inhibitor-1 suppresses early brain injury following experimental subarachnoid hemorrhage in rats.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is an important cause of high mortality and poor prognosis in SAH. B­cell lymphoma 2­associated X protein inhibitor­1 (BI­1) is an evolutionarily conserved antiapoptotic protein that is primarily located in the membranes of endoplasmic reticulum (ER). BI­1 has been studied in certain nervous system­associated diseases, but the role of this protein in SAH remains unclear. In the present study, the role of BI­1 in EBI following SAH was investigated in rat models and its associated mechanisms were examined. The SAH rat model was generated by inserting nylon cords into the internal carotid artery from the external carotid artery. Samples were assessed using neurological scores, brain water content measurements, hematoxylin and eosin (H&E) staining, blood­brain barrier (BBB) permeability, terminal deoxynucleotidyl transferase­mediated dUTP nick­end labeling and quantitative polymerase chain reaction assays, and western blot analyses. It was identified that the mRNA and protein levels of BI­1 decreased markedly and were lowest at 24 h after SAH. BI­1 overexpression and small hairpin RNA (shRNA)­mediated silencing markedly suppressed or severely exacerbated EBI following SAH, respectively. BI­1 overexpression in the SAH model improved neurological scores and decreased the brain water content, BBB permeability and levels of apoptosis compared with the control and sham groups following SAH. BI­1 shRNA in the SAH model demonstrated contrary results. In addition, the mRNA or protein expression levels of ER stress­associated genes (glucose regulated protein, 78 kDa, C/EBP homologous protein, Serine/threonine­protein kinase/endoribonuclease IRE1, c­Jun N terminal kinases and apoptotic signaling kinase­1) were markedly suppressed or increased following BI­1 overexpression and shRNA­mediated silencing, respectively. The present study suggested that BI­1 serves a neuroprotective role in EBI following SAH by attenuating BBB disruption, brain edema and apoptosis mediated by ER stress.

Silver-catalyzed intermolecular amination of fluoroarenes.

A novel highly selective Ag-catalyzed intermolecular amination of fluoroarenes has been developed. This transformation starts from readily available 4-carbonyl fluorobenzene and NaN3 or other nitrogen-source, via amination followed by C-F bond cleavage, thus affording the desired 4-carbonyl arylamine products under mild conditions. The reaction is accelerated using a small amount of water. This pathway is distinct from a previously reported radical amination reaction.

Biosorption of As(V) onto dried alligator weed root: role of metal (hydro) oxides.

The present work investigates the adsorption of As(V) onto the dried powder of alligator weed root as bio-sorbent, using acid pre-treated alligator weed root powder as the reference. The isotherm study suggested there is a favorable As(V) adsorption happened on the AWR surface. The batch adsorption experimental results indicated that the ionic strength has little impact on the adsorption, while the solution pH has a significant effect on the adsorption with apparent inhibition appearing in both extreme acidic and alkaline pH region. In addition, the properties of the biosorbent were characterized by various techniques including SEM-EDS, FT-IR, and ICP detection. The analysis results suggested that the metals including Mn, Fe, and Al enrich over the alligator weed root surface in the morphology of metal (hydro) oxide. Based on the nature of the biosorbent and As(V) besides the adsorption performance, the metal (hydro) oxides over biosorbent surface is suggested as the essential role to drive the adsorption. With the metal (hydro) oxides denuded in the pre-treatment, the biosorbent loses its adsorption capability for As(V) totally.

Tuberculosis bronchopleural fistula treated with atrial septal defect occluder.

Bronchopleural fistula (BPF) is an uncommon and potentially fatal complication of lobectomy or pneumonectomy, particularly in tuberculosis patients. It is associated with high mortality and its treatment remains a challenge. The development of plugging technology has led to the emergence of less invasive endobronchial methods for treating BPF. We describe the successful treatment of a multidrug-resistant tuberculosis patient with BPF using an occlusion device originally designed for transcatheter closure of an atrial septal defect. Follow-up over 10 months revealed maintenance of the repair without any recurrence. This novel technique can be effective for treating a tuberculosis patient with postoperative BPF.

The interaction of blood proteins with brucine.

The features of brucine (BC) binding to two blood proteins, bovine hemoglobin (BHb), and bovine serum albumin (BSA), were investigated via fluorescence, circular dichroism and UV/Vis absorption spectroscopy. The results revealed that BC caused the fluorescence quenching of blood proteins by the formation of BC-protein complex. The corresponding thermodynamic parameters were measured at different temperatures. The process of binding BC molecule on protein was a spontaneous molecular interaction procedure in which entropy increased and Gibbs free energy decreased. Hydrophobic and electrostatic interactions play a major role in stabilizing the complex. The molecular docking has been employed to explore the binding site of the BC in BHb and BSA on the Autodock 4.2. The distances r between BC and protein were calculated to be 4.93 and 5.08 nm for BHb, and BSA, respectively. The effect of BC on the conformation of blood proteins was analyzed using CD, synchronous fluorescence and three-dimensional fluorescence spectra.

[Fixed-bed adsorption characteristics of chlorinated hydrocarbon vapors onto hydrophobic hypercrosslinked polymeric resin].

The dynamic adsorption of trichloroethylene (TCE), 1,2-dichloroethane (DCE) and trichloromethane (TCM) vapors onto hydrophobic hypercrosslinked polymeric resin (LC-1) were investigated using the fixed-bed adsorption method. The results indicated that the breakthrough time decreased and the height of mass transfer zone increased with the elevated initial concentration, gas flow rate and adsorption temperature. The gas flow rate had the wost significant influence on breakthrough time and height of mass transfer zone among the three factors. In addition, a simple semi-empirical mathematic model developed by Yoon and Nelson was applied to investigate the breakthrough behavior, and all correlation coefficients R2 were greater than 0.994.