PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression.

OBJECTIVE: This inquiry endeavors to delineate the influence of PDIA3 on tumor-associated macrophages within the realm of colorectal malignancies, whilst elucidating the intrinsic biochemical pathways. METHOD: Leveraging bioinformatics, we scrutinized the symbiosis between PDIA3, STAT3, and CD274. A xenograft model in immunodeficient murine served to assess PDIA3's impact on colorectal carcinogenesis. Further, Western blot analysis quantified the protein expression of PDIA3, p-STAT3, PD-1, XBP-1, assorted enzymes, and IL-6. Moreover, in vitro assays gauged SW480 cellular dynamics inclusive of migration, invasive potential, and proliferation. RESULTS: Bioinformatics exploration exposed PDIA3's elevated presence in diverse cancers, with a marked expression in colorectal cancer, as per TCGA and GEO repositories. Correlative studies showed PDIA3 positively aligning with STAT3 and CD274, the latter also associated with monocyte-derived macrophages. Comparative analysis of colorectal neoplasms and normal colon samples unveiled heightened levels of PDIA3 markers which, when overexpressed in SW480 cells, escalated tumorigenicity and oncogenic behaviors, with a noted decrease upon PD-1 monoclonal antibody intervention. CONCLUSIONS: PDIA3 augments the M2 polarization of tumor-associated macrophages via modulation of the STAT3/PD-1 cascade, thus invigorating the tumorous proliferation and dissemination in colorectal cancer. Such revelations position PDIA3 as an auspicious target for PD-1 blockade therapeutics, offering a promising foundation for rectifying colorectal carcinoma.

Probucol protects against brain damage caused by intra-neural pyroptosis in rats with vascular dementia through inhibition of the Syk/Ros pathway.

BACKGROUND: Neuronal injury in chronic cerebral hypoperfusion (CCH) is the main pathogenic factor of vascular dementia (VD). Clinically, there isn't a drug specifically for VD; instead, the majority of medications used to treat Alzheimer's disease (AD) are also used to treat VD. Based on the proven anti-inflammatory and antioxidant effects of Probucol, we hypothesized that it may have therapeutic effects on VD, but more research is required to determine its exact mechanism of action. METHODS: In vivo experiment: We used SD rats and most commonly used bilateral carotid artery occlusion (2-VO) in VD for modeling. After successful modeling, SD rats were given Probucol 3.5 mg/kg/day for 8 weeks to evaluate the therapeutic effect. In vitro experiment: BV-2 microglia of rats were cultured and divided into Control group and Probucol group. Each group was treated with hypoxia-hypoglycemia, hypoxia-hypoglycemia hydrogen peroxide and hypoxia-hypoglycemia hydrogen peroxide Syk inhibitor respectively. RESULTS: The results of immunofluorescence and Western blot showed that Probucol could significantly improve the cognitive impairment induced by CCH, and the neuronal damage was also attenuated. On the one hand, the underlying mechanism of Probucol was to reduce oxidative stress and cell apoptosis of hippocampal neurons by inhibiting the expression of phosphorylated spleen tyrosine kinase (P-Syk); On the other hand, it exerted a protective effect by reducing NLRP3-dependent cell pyroptosis and inhibiting neuroinflammation induced by microglia activation. CONCLUSION: Probucol could reduce oxidative stress and cell apoptosis by inhibiting the Syk/ROS signaling pathway, thereby improving CCH-induced cognitive impairment in vitro and in vivo.

Influence of Top Seal Damage on Contact Seal in Ram Blowout Preventer.

Top seal failure of ram blowout preventer (BOP) is one of the main factors leading to well control risk. The constitutive model and parameters of nitrile butadiene rubber (NBR) were optimized by compression and tensile tests, and the failure analysis model of the contact seal of the ram BOP top seal was built. The nonlinear contact mechanical behavior of the connection part of the BOP top seal was analyzed by the finite element method. Then, the influence of corrosion and wear defects at the top seal position of the 2FZ35-70 BOP under rated working pressure on the contact seal were studied, and the results showed that the overall contact pressure distribution of the top seal corrosion defects was uniform, the local contact pressure of the corrosion pit edge increased, and the top contact pressure decreased. The overall contact pressure of the wear defect of the top seal decreased linearly, the contact pressure at the maximum depth of the wear defect was the smallest, and the contact pressure gradually decreased to both sides. Ultimately, to guarantee the safety and reliability of the ram BOP, it is suggested that the acceptable depths of the seal corrosion pit and the wear at the top of the ram BOP are 4.0 mm and 0.2 mm, respectively, thus the reliability evaluation problem of the quantitative seal of the ram BOP top seal is solved.

Buried Defect Detection Method for a Blowout Preventer Seal Ring Groove Based on an Ultrasonic Phased Array.

This study aims to investigate an accurate detection method to detect defects in the gasket ring groove of the blowout preventer (BOP) using the ultrasonic phased array technology. Traditionally, it is difficult to accurately determine the type and size of defects in the gasket ring groove due to the complexity of the BOP configuration and the interference between the defect echo and the structural echo when using the ultrasonic phased array detection technology. In this study, firstly, the appropriate detection process parameters are determined by using simulation software for simulating and analyzing the defects of different sizes and types in the gasket ring groove of a BOP. Thereafter, according to the detection process parameters determined by the simulation analysis, we carry out a corresponding actual detection test. Simulation analysis and detection test results show that the relative amplitude of the test results and the simulation results differ within 1 dB, and the simulation results have a guiding role for the actual detection. The defect echo and structure echo can be clearly distinguished by selecting appropriate detection process parameters, such as probe frequency 5 MHz, array elements 36, and probe aperture 16 mm. The research results can provide theoretical reference for the detection of blowout preventer.

Effect of Kaempferol on the Biological Behavior of Human Colon Cancer via Regulating MMP1, MMP2, and MMP9.

Kaempferol is a kind of flavonoid, which has a significant anticancer effect. MMPs were discovered with the function of cleaving the extracellular matrix. We utilized bioinformatics to analyze the association and bonding mode between the traditional Chinese medicine (TCM) monomer composition (i.e., kaempferol) and the target proteins. The purpose of our research was to verify the effect of kaempferol on the biological behavior of human colon cancer cells HCT116 and HT29 and the expression of matrix metalloproteinase (MMP) 1, 2, and 9 genes. We detected the changes in the biological behavior of colon cancer cells treated with kaempferol by CCK-8, wound healing assay, transwell migration/invasion assay, and flow cytometry. Meanwhile， we detected the expression difference of the target gene by qRT-PCR and western blot. Compared with the two control groups, the cell viability of the kaempferol group decreased, the rate of cell migration and the number of transmembrane cells in the kaempferol group decreased significantly, and the early apoptosis rate increased, the number of cells in the G1 phase increased and in the S phase decreased. The results of qRT-PCR and western blot showed that the expression of target genes MMP1, 2, and 9 in the kaempferol group was lower than that in the two control groups. Kaempferol can significantly inhibit the proliferation, invasion, and migration ability of colon cancer cells; induce their apoptosis; and block the cell cycle. Meanwhile, the expression of MMP1, 2, and 9 genes was downregulated, which verified the results of bioinformatic analysis.

Experimental study on ignition mechanisms of wet granulation sulfur caused by friction.

It is common to see fire accidents caused by friction during the storage and transportation of wet granulation sulfur. To study the sulfur ignition mechanism under friction conditions, a new rotating test apparatus is developed to reproduce friction scenes at lab scale. A series of experiments are performed under different normal loads. The SEM-EDS and the XRD were utilized to examine the morphologies and compositions of the tested specimens and the friction products. Experimental results show that these two methods are mostly in agreement with each other. The iron-sulfide compounds are produced and the proportion of iron-sulfide compounds is reduced with normal loads increasing, compared to the total number of the friction products. The facts implied by the integration analysis of friction products with the temperature changes of the near friction surface unveil an underlying mechanism that may explain sulfur ignition by friction in real scenarios. The sulfur ignition may be mainly caused by the spontaneous combustion of iron sulfide compounds produced by friction under low normal load with 200N. With the increase of normal loads, the resulting iron-sulfide compounds are decreasing and the high temperature from friction heat begins to play a major role in causing fire.

Comparative Transcriptomic Analysis of Two Brassica napus Near-Isogenic Lines Reveals a Network of Genes That Influences Seed Oil Accumulation.

Rapeseed (Brassica napus) is an important oil seed crop, providing more than 13% of the world's supply of edible oils. An in-depth knowledge of the gene network involved in biosynthesis and accumulation of seed oil is critical for the improvement of B. napus. Using available genomic and transcriptomic resources, we identified 1,750 acyl-lipid metabolism (ALM) genes that are distributed over 19 chromosomes in the B. napus genome. B. rapa and B. oleracea, two diploid progenitors of B. napus, contributed almost equally to the ALM genes. Genome collinearity analysis demonstrated that the majority of the ALM genes have arisen due to genome duplication or segmental duplication events. In addition, we profiled the expression patterns of the ALM genes in four different developmental stages. Furthermore, we developed two B. napus near isogenic lines (NILs). The high oil NIL, YC13-559, accumulates significantly higher (∼10%) seed oil compared to the other, YC13-554. Comparative gene expression analysis revealed upregulation of lipid biosynthesis-related regulatory genes in YC13-559, including SHOOTMERISTEMLESS, LEAFY COTYLEDON 1 (LEC1), LEC2, FUSCA3, ABSCISIC ACID INSENSITIVE 3 (ABI3), ABI4, ABI5, and WRINKLED1, as well as structural genes, such as ACETYL-CoA CARBOXYLASE, ACYL-CoA DIACYLGLYCEROL ACYLTRANSFERASE, and LONG-CHAIN ACYL-CoA SYNTHETASES. We observed that several genes related to the phytohormones, gibberellins, jasmonate, and indole acetic acid, were differentially expressed in the NILs. Our findings provide a broad account of the numbers, distribution, and expression profiles of acyl-lipid metabolism genes, as well as gene networks that potentially control oil accumulation in B. napus seeds. The upregulation of key regulatory and structural genes related to lipid biosynthesis likely plays a major role for the increased seed oil in YC13-559.

Dynamic transcriptome analysis reveals AP2/ERF transcription factors responsible for cold stress in rapeseed (Brassica napus L.).

The APETALA2/ethylene response factor (AP2/ERF) transcription factor (TF) superfamily plays an important regulatory role in signal transduction of the plant responses to various stresses including low temperature. Significant progress has been made in understanding the mechanism of cold resistance in Brassica napus, an important oilseed crop. However, comprehensive studies on the induction and activity of these TFs under low temperature have been lacking. In this study, 132 AP2/ERF genes were identified by transcriptome sequencing of rapeseed leaves exposed to 0, 2, 6, 12, and 24 h of low (4 °C) temperature stress. The genes were classified into 4 subfamilies (AP2, DREB, ERF, and RAV) and 13 subgroups, among which the DREB subfamily and ERF subfamily contained 114 genes, no genes were assigned to soloist or DREB A3 subgroups. One hundred and eighteen genes were located on chromosomes A1 to C9. GO functional analysis and promoter sequence analysis revealed that these genes are involved in many molecular pathways that may enhance cold resistance in plants, such as the low-temperature responsiveness, methyl jasmonate, abscisic acid, and ethylene-responsiveness pathways. Their expression patterns revealed dynamic control at different times following initiation of cold stress; the RAV and DREB subfamilies were expressed at the early stage of cold stress, whereas the AP2 subfamily was expressed later. Quantitative PCR analyses of 13 cold-induced AP2/ERF TFs confirmed the accuracy of above results. This study is the first dynamic analysis of the AP2/ERF TFs responsible for cold stress in rapeseed. These findings will serve as a reference for future functional research on transcription in rapeseed.

[Study on the virus-free technology of Pinellia temata].

OBJECTIVE: To solve the degradation of production and quality of Pinellia caused by the virus accumulation, rapid propagation technical of virus-free Pinellia was researched. METHODS: Pinellia leaves,petioles as explants, technology of using high temperature (38 degrees C, 40d) and shoot tip culture producing virus-free Pinellia was explored. RESULTS: The results showed that leaves without virus spots was about 88.9% when explants were culture for 40d at high temperature (38 degrees C). 1.0 mg/L 6-BA and 0.1 mg/L NAA could induce seedling from shoot tip,seedling rate is up to 91.4%; MS added 0.5 mg/L 6-BA and 0.1 mg/L NAA was conducive to growth of the plantlets; added 0.5 mg/L KT and 0.5 mg/L NAA was in favor of inducing root and promoting root growth, the survival rate of the transplanting seedling could reach 89.5%. CONCLUSION: A reliable system of virus-free Pinellia propagation is established.