Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphism and Susceptibility of Minimal Change Nephrotic Syndrome: A Meta-Analysis

Aim. This meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and MCNS susceptibility. Method. A predefined literature search and selection of eligible relevant studies were performed to collect the data from electronic databases. Results. Six articles were identified for the analysis of association between ACE I/D gene polymorphism and MCNS risk, including 4 for Asians, one in Caucasian population and one for Africans. There was a markedly positive association between D allele or DD genotype and MCNS susceptibility in Asians (D: P = .01, DD: P = .02), but not for Caucasians and Africans (Caucasians: D: P = .16, DD: P = .98; Africans: D: P = .81, DD: P = .49). Furthermore, the II genotype seemed not to play a protective role against MCNS risk for Asians, Caucasians and Africans (P = .12, P = .09, P = .76, resp.). Interestingly, there was also significant association between ACE I/D gene polymorphism and MCNS susceptibility in overall populations (D: P = .007, DD: P = .04, II: P = .03). Conclusion. D allele or DD genotype might be a significant genetic molecular marker for MCNS susceptibility in Asians and overall populations, but not for Caucasians and Africans. More larger and rigorous genetic epidemiological investigations are required to further explore this association

Whole-exome sequencing identifies susceptibility genes and pathways for idiopathic pulmonary fibrosis in the Chinese population

Genetic factors play a role in the risk of idiopathic pulmonary fibrosis (IPF). Specifically, MUC5B rs35705950 non-risk alleles and immunologic aberrations were associated with the IPF’s progression. However, rare genetic variants have not been systematically investigated in Chinese IPF patients. In this study, we aimed to improve understanding of the genetic architecture of IPF in the Chinese population and to assess whether rare protein-coding variants in the immunity pathway genes are enriched in the IPF patients with non-risk alleles at rs35705950. A case–control exome-wide study including 110 IPF patients and 60 matched healthy controls was conducted. rs35705950 was genotyped by Sanger sequencing. To identify genes enriched in IPF, gene-based association analyses were performed. Identified genes were included for further pathway analyses using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Associations between rs35705950 and genes enriched in the immunity pathway were also tested. 226 genes that were enriched with deleterious variants were identified in IPF patients. Out of them, 36 genes were significantly enriched in GO and KEGG pathways in the IPF. Pathway analyses implicated that these genes were involved in the immune response and cell adhesion. Rare protein-altering variants in genes related to the immunity pathway did not significantly differ between patients with a MUC5B risk allele and individuals without risk allele. We drafted a comprehensive mutational landscape of rare protein-coding variants in the Chinese IPF and identified genes related to immune response and cell adhesion. These results partially explain changes in gene expression involved in the immunity/inflammatory pathways in IPF patients

Diffuse gamma-ray emission toward the massive star-forming region, W40

We report the detection of high-energy gamma-ray signal towards the young star-forming region, W40. Using 10-year Pass 8 data from the Fermi Large Area Telescope (Fermi-LAT), we extracted an extended gamma-ray excess region with a significance of about 18sigma. The radiation has a spectrum with a photon index of 2.49 +/- 0.01. The spatial correlation with the ionized gas content favors the hadronic origin of the gamma-ray emission. The total cosmic-ray (CR) proton energy in the gamma-ray production region is estimated to be the order of 10^47 erg. However, this could be a small fraction of the total energy released in cosmic rays (CRs) by local accelerators, presumably by massive stars, over the lifetime of the system. If so, W40, together with earlier detections of gamma-rays from Cygnus cocoon, Westerlund 1, Westerlund 2, NGC 3603, and 30 Dor C, supports the hypothesis that young star clusters are effective CR factories. The unique aspect of this result is that the gamma-ray emission is detected, for the first time, from a stellar cluster itself, rather than from the surrounding "cocoons".Comment: 8 pages, 7 figures, accepted for publication in A&

ECHS1 interacts with STAT3 and negatively regulates STAT3 signaling

AbstractSignal transducer and activator of transcription 3 (STAT3) is a critical transcriptional factor in a variety of cellular processes, and is frequently over-activated in a range of human tumors. However, the processes that regulate STAT3 activation need to be further clarified. With a yeast two-hybrid screening, we identified enoyl-CoA hydratase short chain 1 (ECHS1) as a novel STAT3 binding protein. We further confirmed the interaction between STAT3 and ECHS1 by GST-pull down and co-immnunoprecipitation. Importantly, we found that ECHS1 specifically represses STAT3 activity and negatively regulates the expression of several target genes of STAT3 through inhibiting STAT3 phosphorylation. Therefore, our findings will provide new insights into the mechanism of STAT3 signaling regulation.Structured summary of protein interactionsSTAT3physically interactswithECHS1bypull down(View interaction)STAT3physically interactswithECHS1bytwo hybrid(View Interaction:1,2)ECHS1physically interactswithSTAT3byanti tag co immunoprecipitation(View Interaction:1,2)STAT3physically interactswithECHS1byanti bait co immunoprecipitation(View interaction

Case Report: A novel intergenic MIR4299/MIR8070-RET fusion with RET amplification and clinical response to pralsetinib in a lung adenocarcinoma patient

The identification of receptor-tyrosine kinase gene (RET) fusions in lung cancer has become crucial owing to actionable events that predict responsiveness to tyrosine kinase inhibitors (TKIs). However, RET fusions with distinct partner genes respond differently to TKIs. In this case, a 60-year-old man was diagnosed with advanced lung adenocarcinoma. A novel RET-MIR4299/MIR8070 fusion and RET amplification were identified using next-generation sequencing (NGS). The patient was then administered with pralsetinib. After 3 weeks of therapy, the patient had a partial response. At the time of reporting, the patient was on continuous pralsetinib. These findings broaden the range of RET fusion types and provide the basis for the hypothesis that RET intergenic fusion and amplification respond to pralsetinib treatment in lung adenocarcinoma

Novel octopus shaped organic-inorganic composite membranes for PEMFCs

© 2016 Hydrogen Energy Publications LLC.Phosphoric acid doped polybenzimidazoles are among the most interesting proton exchange membrane materials for high temperature proton exchange membrane fuel cell applications. As a major challenge the proton conducting decline due to free phosphoric acid leaching during the long term fuel cell operation is addressed by fixing overmuch phosphoric acid in the polymer matrix. Novel organic-inorganic composite membranes are prepared via in situ synthesis of poly(2,5-benzimidazole) (ABPBI) and OctaAmmonium POSS (AM-POSS) hybrid composites (ABPBI/AM-POSS) following phosphoric acid doping and membrane casting procedures. Compared with the pristine ABPBI membrane, the introduction of AM-POSS into ABPBI polymer membrane caused water and phosphoric acid absorbilities increasing dramatically, resulting in the significant increase of proton conductivities at whether hydrous or anhydrous condition. ABPBI/3AM composite membranes with phosphoric acid uptake above 250% showed best proton conductivities from room temperature to 160 °C, indicating these composite membranes could be excellent candidates as a polymer electrolyte membrane for low and intermediate temperature applications

Clinical features and therapeutic outcomes of GH/TSH cosecreting pituitary adenomas: experience of a single pituitary center

BackgroundGrowth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported.ObjectivesThis study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center.MethodsWe retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital’s information system.ResultsBased on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P <0.001). In addition, higher occurrence rates of arrhythmia (28.6% vs. 2.4%, P = 0.004), heart enlargement (33.3% vs. 4.8%, P = 0.005) and osteopenia/osteoporosis (33.3% vs. 2.4%, P = 0.001) were observed in the mixed PA group.ConclusionThere are great challenges in the treatment and management of GH/TSH cosecreting PA. Early diagnosis, multidisciplinary therapy and careful follow-up are required to improve the prognosis of this bihormonal PA