Oxide Dispersion Strengthened (ODS) SS316L Prepared by Laser Powder Bed Fusion (L-PBF): Analysis of Microstructure and Hardness Properties

In this paper, dense oxide dispersion-strengthened (ODS) SS316L with 0.5 wt.% Y2O3 was fabricated using nano-Y2O3-embedded spherical SS316L powder via laser powder bed fusion (LPBF). The molten pool, oxide dispersion, cellular structure, and microhardness of the as-printed ODS SS316L were investigated through optical microscopy (OM), scanning electron microscopy (SEM), energy dispersive X-Ray Spectroscopy (EDX), and Vickers hardness testing, respectively. The results reveal a uniform dispersion of Y-rich nanoparticles in as-printed ODS SS316L, contributing to the development of a fine-grain structure in the as-printed ODS SS316L. A wide and shallow molten pool was observed in as-printed ODS SS316L, and enhanced microhardness was observed in ODS SS316L compared to pristine SS316L. The effects of Y2O3 on microstructure evolution and reinforcing mechanisms of microhardness are discussed.Mechanical Engineerin

Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism

Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases

N-benzyl-N-methyldecan-1-amine and its derivative mitigate 2,4- dinitrobenzenesulfonic acid-induced colitis and collagen-induced rheumatoid arthritis

As our previous study revealed that N-benzyl-N-methyldecan-1-amine (BMDA), a new molecule originated from Allium sativum, exhibits anti-neoplastic activities, we herein explored other functions of the compound and its derivative [decyl-(4-methoxy-benzyl)-methyl-amine; DMMA] including anti-inflammatory and anti-oxidative activities. Pretreatment of THP-1 cells with BMDA or DMMA inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-1β production, and blocked c-jun terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), MAPKAP kinase (MK)2 and NF-κΒ inflammatory signaling during LPS stimulation. Rectal treatment with BMDA or DMMA reduced the severity of colitis in 2,4-dinitrobenzenesulfonic acid (DNBS)-treated rat. Consistently, administration of the compounds decreased myeloperoxidase (MPO) activity (representing neutrophil infiltration in colonic mucosa), production of inflammatory mediators such as cytokine-induced neutrophil chemoattractant (CINC)-3 and TNF-α, and activation of JNK and p38 MAPK in the colon tissues. In addition, oral administration of these compounds ameliorated collagen-induced rheumatoid arthritis (RA) in mice. The treatment diminished the levels of inflammatory cytokine transcripts, and protected connective tissues through the expression of anti-oxidation proteins such as nuclear factor erythroid-related factor (Nrf)2 and heme oxygenase (HO)1. Additionally, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not differ between the BMDA- or DMMA-treated and control animals, indicating that the compounds do not possess liver toxicity. Taken together, these findings propose that BMDA and DMMA could be used as new drugs for curing inflammatory bowel disease (IBD) and RA

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Prognostic Value of Long Noncoding RNAs in Patients with Gastrointestinal Cancer: A Systematic Review and Meta-Analysis

Gastrointestinal cancers (GICs) are a huge threat to human health, which mainly include esophageal, gastric, and colorectal cancers. The purpose of this study was to clarify the prognostic value of long noncoding RNAs (lncRNAs) in GICs. A total of 111 articles were included, and 13103 patients (3123 with esophageal cancer, 4972 with gastric cancer, and 5008 with colorectal cancer) were enrolled in this study. The pooled hazard ratio (HR) values and corresponding 95% confidence interval (95% CI) of overall survival (OS) related to different lncRNA expressions in esophageal, gastric, colorectal, and gastrointestinal cancer patients were 1.92 (1.70–2.16), 1.96 (1.77–2.16), 2.10 (1.87–2.36), and 2.00 (1.87–2.13), respectively. We have identified 74 lncRNAs which were associated closely with poor prognosis of GIC patients, including 58 significantly upregulated lncRNA expression and 16 significantly downregulated lncRNA expression. In addition, 47 of the included studies revealed relative mechanisms and 12 of them investigated the correlation between lncRNAs and microRNAs. Taken together, this meta-analysis supports that specific lncRNAs are significantly related to the prognosis of GIC patients and may serve as novel markers for predicting the prognosis of GIC patients. Furthermore, lncRNAs may have a promising contribution to lncRNA-based targeted therapy and clinical decision-making in the future

Highly Accurate Frequency Quadrupler Based LO Phase Shifter Achieving 0.29° RMS Phase Error for Wideband E-band Beamforming Receiver

Despite several advantages in terms of linearity and operating bandwidth, LO phase-shifting is not widely used in beamforming transceivers due to the difficulty in realizing fine phase resolution. Regarding the use of a M frequency multiplier, the phase resolution at fLO/M should be much higher than that desired at fLO. Here, we propose a frequency multiplier based LO phase-shifting technique that does not reduce the phase resolution after the frequency multiplication. At the cost of a few phase states out of 2n, the phase resolution at fLO/M can be retained after the frequency multiplier. For experimental evaluation, the proposed scheme was implemented in an E-band beamforming receiver. Because the proposed scheme is suitable for fine resolution and broadband transceivers at millimeter-wave frequencies, the bandwidth of the receiver reaches as high as 23 GHz at 77 GHz with phase resolution and rms phase error of 2.835° and 0.29°, respectively.1

Small Nucleolar RNAs and Their Comprehensive Biological Functions in Hepatocellular Carcinoma

Small nucleolar RNAs (snoRNAs) are a class of highly conserved, stable non-coding RNAs involved in both post-transcriptional modification of RNA and in ribosome biogenesis. Recent research shows that the dysfunction of snoRNAs plays a pivotal role in hepatocellular carcinoma (HCC) and related etiologies, such as hepatitis B virus (HBV), hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD). Growing evidence suggests that snoRNAs act as oncogenes or tumor suppressors in hepatocellular carcinoma (HCC) through multiple mechanisms. Furthermore, snoRNAs are characterized by their stability in body fluids and their clinical relevance and represent promising tools as diagnostic and prognostic biomarkers. SnoRNAs represent an emerging area of cancer research. In this review, we summarize the classification, biogenesis, activity, and functions of snoRNAs, as well as highlight the mechanism and roles of snoRNAs in HCC and related diseases. Our findings will aid in the understanding of complex processes of tumor occurrence and development, as well as suggest potential diagnostic markers and treatment targets. Furthermore, we discuss several limitations and suggest future research and application directions

Eletrophilic Chemistry of Tranilast Is Involved in Its Anti-Colitic Activity via Nrf2-HO-1 Pathway Activation

Tranilast (TRL), a synthetic derivative of a tryptophan metabolite, is an anti-allergic drug used to treat bronchial asthma. We investigated how TRL activated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)-hemeoxygenase-1 (HO-1) pathway based on the electrophilic chemistry of the drug and whether TRL activity contributed to the treatment of rat colitis. In human colon carcinoma cells, TRL activated Nrf2, as represented by an increase in nuclear Nrf2 and induction of Nrf2-dependent luciferase and, subsequently, HO-1, a target gene product of Nrf2. TRL activation of Nrf2 and induction of HO-1 were completely prevented by chemical reduction of the electrophilic functional group (α, β-unsaturated carbonyl group) in the drug. In parallel, TRL was reactive with the nucleophilic thiol group in N-acetylcysteine, forming a covalent adduct. Moreover, TRL, but not reduced TRL, binds to Kelch-like ECH-associated protein 1 (KEAP1), releasing Nrf2. TRL administration ameliorated colonic damage and inflammation in rats with dinitrobenzene sulfonic acid-induced colitis, which was partly compromised by the chemical reduction of TRL or co-treatment with an HO-1 inhibitor. Our results suggest that TRL activated the Nrf2-HO-1 pathway via covalent binding to KEAP1, partly contributing to TRL amelioration in rat colitis