Bioinformatics-based analysis of the roles of basement membrane-related gene AGRN in systemic lupus erythematosus and pan-cancer development

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease involving many systems and organs, and individuals with SLE exhibit unique cancer risk characteristics. The significance of the basement membrane (BM) in the occurrence and progression of human autoimmune diseases and tumors has been established through research. However, the roles of BM-related genes and their protein expression mechanisms in the pathogenesis of SLE and pan-cancer development has not been elucidated.MethodsIn this study, we applied bioinformatics methods to perform differential expression analysis of BM-related genes in datasets from SLE patients. We utilized LASSO logistic regression, SVM-RFE, and RandomForest to screen for feature genes and construct a diagnosis model for SLE. In order to attain a comprehensive comprehension of the biological functionalities of the feature genes, we conducted GSEA analysis, ROC analysis, and computed levels of immune cell infiltration. Finally, we sourced pan-cancer expression profiles from the TCGA and GTEx databases and performed pan-cancer analysis.ResultsWe screened six feature genes (AGRN, PHF13, SPOCK2, TGFBI, COL4A3, and COLQ) to construct an SLE diagnostic model. Immune infiltration analysis showed a significant correlation between AGRN and immune cell functions such as parainflammation and type I IFN response. After further gene expression validation, we finally selected AGRN for pan-cancer analysis. The results showed that AGRN’s expression level varied according to distinct tumor types and was closely correlated with some tumor patients’ prognosis, immune cell infiltration, and other indicators.DiscussionIn conclusion, BM-related genes play a pivotal role in the pathogenesis of SLE, and AGRN shows immense promise as a target in SLE and the progression of multiple tumors

Two Novel AGXT Mutations Cause the Infantile Form of Primary Hyperoxaluria Type I in a Chinese Family: Research on Missed Mutation

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype–genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family

Electrical properties of yttrium calcium oxyborate crystal annealed at high temperature and low oxygen partial pressure

The yttrium calcium oxyborate crystal (YCa 4 O(BO 3 ) 3 , YCOB) has been actively studied for high-temperature piezoelectric sensing applications. In this work, the stability of electric properties of YCOB crystal annealed in critical conditions (high-temperatures of 900-1100 °C with a low oxygen partial pressure of 4 x 10 −6 atm for 24 h) was investigated and the recovery mechanism for the electrical resisitivity, dielectric permittivity and dielectric loss were studied, taking advantage of the X-ray photoelectron spectra and the first principle calculations. The electrical resistivity of the annealed YCOB crystal was slightly decreased when compared to the pristine counterpart, being (2-5) x 10 7 Ω cm at 850 °C. The dielectric permittivity and dielectric loss were found to increase after annealing, showing recoverable behaviours after thermal treatment above 650 °C in air. The calculated vacancy formation energy indicate that the oxygen vacancy is the dominant defects in YCOB. The formation of oxygen vacancy weakens the chemical bonding strength between B (Ca or Y) and O atoms, introduces extra donor levels in the band gap, which excites the electrons to conduction band more easily thus enhances the electrical conductivity and dielectric loss. The recovered electrical properties are believed to be associated with the reduced vacancy defects at elevated temperatures in air

Inflammation-Related Cytokines of Aqueous Humor in Acute Primary Angle-Closure Eyes

PURPOSE. To measure levels of various inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure (APAC) and senile cataract. METHODS. Aqueous humor samples were prospectively collected from 23 eyes (12 eyes with current APAC and 11 eyes with previous APAC) of 23 APAC patients and 15 eyes of 15 cataract patients. The levels of 15 inflammation-related cytokines in the aqueous humor of APAC and cataract subjects were measured by using the multiplex bead immunoassay technique. Data on patient demographics and preoperative intraocular pressure (IOP) were also collected for correlation analysis

Response of soil bacterial communities in wheat rhizosphere to straw mulching and N fertilization

Straw mulching and N fertilization are effective in augmenting crop yields. Since their combined effects on wheat rhizosphere bacterial communities remain largely unknown, our aim was to assess how the bacterial communities respond to these agricultural measures. We studied wheat rhizosphere microbiomes in a split-plot design experiment with maize straw mulching (0 and 8,000 kg straw ha−1) as the main-plot treatment and N fertilization (0, 120 and 180 kg N ha−1) as the sub-plot treatment. Bacterial communities in the rhizosphere were analyzed using 16S rRNA gene amplicon sequencing and quantitative PCR. Most of the differences in soil physicochemical properties and rhizosphere bacterial communities were detected between the straw mulching (SM) and no straw mulching (NSM) treatments. The contents of soil organic C (SOC), total N (TN), NH4+-N, available N (AN), available P (AP) and available K (AK) were higher with than without mulching. Straw mulching led to greater abundance, diversity and richness of the rhizosphere bacterial communities. The differences in bacterial community composition were related to differences in soil temperature and SOC, AP and AK contents. Straw mulching altered the soil physiochemical properties, leading to greater bacterial diversity and richness of the rhizosphere bacterial communities, likely mostly due to the increase in SOC content that provided an effective C source for the bacteria. The relative abundance of Proteobacteria was high in all treatments and most of the differentially abundant OTUs were proteobacterial. Multiple OTUs assigned to Acidobacteria, Chloroflexi and Actinobacteria were enriched in the SM treatment. Putative plant growth promoters were enriched both in the SM and NSM treatments. These findings indicate potential strategies for the agricultural management of soil microbiomes

Discovery and identification of potential biomarkers of pediatric Acute Lymphoblastic Leukemia

<p>Abstract</p> <p>Background</p> <p>Acute lymphoblastic leukemia (ALL) is a common form of cancer in children. Currently, bone marrow biopsy is used for diagnosis. Noninvasive biomarkers for the early diagnosis of pediatric ALL are urgently needed. The aim of this study was to discover potential protein biomarkers for pediatric ALL.</p> <p>Methods</p> <p>Ninety-four pediatric ALL patients and 84 controls were randomly divided into a "training" set (45 ALL patients, 34 healthy controls) and a test set (49 ALL patients, 30 healthy controls and 30 pediatric acute myeloid leukemia (AML) patients). Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS). A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays.</p> <p>Results</p> <p>A total of 7 protein peaks (9290 m/z, 7769 m/z, 15110 m/z, 7564 m/z, 4469 m/z, 8937 m/z, 8137 m/z) were found with differential expression levels in the sera of pediatric ALL patients and controls using SELDI-TOF-MS and then analyzed by BPS to construct a classification model in the "training" set. The sensitivity and specificity of the model were found to be 91.8%, and 90.0%, respectively, in the test set. Two candidate protein peaks (7769 and 9290 m/z) were found to be down-regulated in ALL patients, where these were identified as platelet factor 4 (PF4) and pro-platelet basic protein precursor (PBP). Two other candidate protein peaks (8137 and 8937 m/z) were found up-regulated in the sera of ALL patients, and these were identified as fragments of the complement component 3a (C3a).</p> <p>Conclusion</p> <p>Platelet factor (PF4), connective tissue activating peptide III (CTAP-III) and two fragments of C3a may be potential protein biomarkers of pediatric ALL and used to distinguish pediatric ALL patients from healthy controls and pediatric AML patients. Further studies with additional populations or using pre-diagnostic sera are needed to confirm the importance of these findings as diagnostic markers of pediatric ALL.</p

Perbandingan Perhitungan Trafik Jam Sibuk CDMA 2000 1x Pada BTS Inner City Dan BTS Outer City Dengan Mempergunakan Metode ADPH, TCBH, FDMH Dan FDMP

Cellular communication system is a wireless communication system where the subscriber can move within a wide network coverage. Code Division Multiple Access (CDMA) is a multiuser access technology that is each user uses a unique code contained in the access channel in the system. Calculation and determination of peak hours can be done by several methods such as: Average Daily Peak Hour (ADPH), Time Consistent Busy Hour (TCBH), Fixed Daily Measurement Hour (FDMH), Fixed Daily Measurement Period (FDMP). The effectiveness of the channel should be determined by occupancy both at inner city territory and outer city &nbsp;territory location. Using design Erlang (Erl) for supply channel at Base Transceiver Station (BTS) that provided, BTS has a design Erlang of 369,83 Erl at inner city and it has a design Erlang of 241,8 Erl at outer city. Peak hour on the inner city occurred at 12:00 to 15:00, whereas the outer city of peak hour occurred at 18:00 to 21:00. Effectiveness value that determined by operator are : &lt;20% = low occupancy (not effective), 21% to 69% = normal occupancy (effective), and &gt; 70% = high occupancy (very effective). In this case occupancy values obtained in each method is between 21% to 69% which means effectiv

The FilZ protein contains a single PilZ domain and facilitates the swarming motility of pseudoalteromonas sp. SM9913

Swarming regulation is complicated in flagellated bacteria, especially those possessing dual flagellar systems. It remains unclear whether and how the movement of the constitutive polar flagellum is regulated during swarming motility of these bacteria. Here, we report the downregulation of polar flagellar motility by the c-di-GMP effector FilZ in the marine sedimentary bacterium Pseudoalteromonas sp. SM9913. Strain SM9913 possesses two flagellar systems, and filZ is located in the lateral flagellar gene cluster. The function of FilZ is negatively controlled by intracellular c-di-GMP. Swarming in strain SM9913 consists of three periods. Deletion and overexpression of filZ revealed that, during the period when strain SM9913 expands quickly, FilZ facilitates swarming. In vitro pull-down and bacterial two-hybrid assays suggested that, in the absence of c-di-GMP, FilZ interacts with the CheW homolog A2230, which may be involved in the chemotactic signal transduction pathway to the polar flagellar motor protein FliMp, to interfere with polar flagellar motility. When bound to c-di-GMP, FilZ loses its ability to interact with A2230. Bioinformatic investigation indicated that filZ-like genes are present in many bacteria with dual flagellar systems. Our findings demonstrate a novel mode of regulation of bacterial swarming motility

Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.

Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies