25-hydroxycholesterol (25-HC) plays a role in the regulation of cell survival and immunity. However, the effect of 25-HC on myocardial ischemia/reperfusion (MI/R) injury remains unknown. Our present study aimed to investigate whether 25-HC aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. The overlapping differentially expressed genes (DEGs) in MI/R were identified from the GSE775, GSE45818, GSE58486, and GSE46395 datasets in Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the database of Annotation, Visualization and Integration Discovery (DAVID). The protein-protein interaction (PPI) network of the overlapping DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database. These bioinformatics analyses indicated that cholesterol 25-hydroxylase (CH25H) was one of the crucial genes in MI/R injury. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to simulate MI/R injury. Western blot and RT-qPCR analysis demonstrated that CH25H was significantly upregulated in OGD/R-stimulated H9C2 cardiomyocytes. Moreover, knockdown of CH25H inhibited the OGD/R-induced pyroptosis and nod-like receptor protein 3 (NLRP3) inflammasome activation, as demonstrated by cell counting kit-8 (CCK8), lactate dehydrogenase (LDH), RT-qPCR, and western blotting assays. Conversely, 25-HC, which is synthesized by CH25H, promoted activation of NLRP3 inflammasome in OGD/R-stimulated H9C2 cardiomyocytes. In addition, the NLRP3 inhibitor BAY11-7082 attenuated 25-HC-induced H9C2 cell injury and pyroptosis under OGD/R condition. In conclusion, 25-HC could aggravate OGD/R-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cells. 25hydroxycholesterol hydroxycholesterol 25 25HC HC (25-HC immunity However ischemiareperfusion ischemia reperfusion MIR MI R (MI/R unknown NLRP inflammasomemediated mediated (DEGs GSE775 GSE GSE45818 GSE58486 GSE4639 GEO (GEO GO (GO KEGG (KEGG Annotation DAVID. DAVID . (DAVID) proteinprotein PPI (PPI STRING (STRING 25hydroxylase hydroxylase CHH CH H (CH25H oxygenglucose oxygen glucose deprivationreoxygenation deprivation reoxygenation OGDR OGD (OGD/R RTqPCR RT qPCR OGD/Rstimulated OGDRstimulated stimulated C H9C cardiomyocytes Moreover OGD/Rinduced OGDRinduced induced nodlike nod like (NLRP3 kit8 kit 8 kit- CCK8, CCK8 CCK , (CCK8) LDH, LDH (LDH) RTqPCR, qPCR, assays Conversely 25HC, HC, addition BAY117082 BAY BAY11 7082 BAY11-708 25HCinduced HCinduced condition conclusion cells 2 GSE77 GSE4581 GSE5848 GSE463 (DAVID Rstimulated Rinduced (NLRP (CCK8 (LDH BAY11708 BAY1 708 BAY11-70 GSE7 GSE458 GSE584 GSE46 (CCK BAY1170 70 BAY11-7 GSE45 GSE58 GSE4 BAY117 7 BAY11- GSE5

Abstract Background Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. Methods In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. Results There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. Conclusion PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease. NICCD, , (NICCD) earlyage early age dysfunction (PCT damage singlecenter single center casecontrol case 12 group ROC (ROC p 0.05. 005 0.05 . 0 05 0.05) cutoff cut off 0495 495 0.49 ngmL ng mL ng/mL 908 90 8 90. 983 98 3 98. (NICCD 1 00 0.0 049 49 0.4 9 0. 04 4

Abstract Human periodontal ligament stem cells (hPDLSCs) are promising cells for dental and periodontal regeneration. Objective This study aimed to develop novel alginate-fibrin fibers that encapsulates hPDLSCs and metformin, to investigate the effect of metformin on the osteogenic differentiation of hPDLSCs, and to determine the regulatory role of the Shh/Gli1 signaling pathway in the metformin-induced osteogenic differentiation of hPDLSCs for the first time. Methodology CCK8 assay was used to evaluate hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red S staining, and the expression of osteogenic genes were evaluated. Metformin and hPDLSCs were encapsulated in alginate-fibrinogen solutions, which were injected to form alginate-fibrin fibers. The activation of Shh/Gli1 signaling pathway was examined using qRT-PCR and western blot. A mechanistic study was conducted by inhibiting the Shh/Gli1 pathway using GANT61. Results The administration of 50 μM metformin resulted in a significant upregulation of osteogenic gene expression in hPDLSCs by 1.4-fold compared to the osteogenic induction group (P < 0.01), including ALP and runt-related transcription factor-2 (RUNX2). Furthermore, metformin increased ALP activity by 1.7-fold and bone mineral nodule formation by 2.6-fold (P<0.001). We observed that hPDLSCs proliferated with the degradation of alginate-fibrin fibers, and metformin induced their differentiation into the osteogenic lineage. Metformin also promoted the osteogenic differentiation of hPDLSCs by upregulating the Shh/Gli1 signaling pathway by 3- to 6- fold compared to the osteogenic induction group (P<0.001). The osteogenic differentiation ability of hPDLSCs were decreased 1.3- to 1.6-fold when the Shh/Gli1 pathway was inhibited, according to ALP staining and alizarin red S staining (P<0.01). Conclusions Metformin enhanced the osteogenic differentiation of hPDLSCs via the Shh/Gli1 signaling pathway. Degradable alginate-fibrin hydrogel fibers encapsulating hPDLSCs and metformin have significant potential for use in dental and periodontal tissue engineering applications. Clinical Significance Alginate-fibrin fibers encapsulating hPDLSCs and metformin have a great potential for use in the treatment of maxillofacial bone defects caused by trauma, tumors, and tooth extraction. Additionally, they may facilitate the regeneration of periodontal tissue in patients with periodontitis. (hPDLSCs alginatefibrin alginate fibrin ShhGli1 ShhGli Shh Gli1 Gli Shh/Gli metformininduced time CCK (ALP evaluated alginatefibrinogen fibrinogen solutions qRTPCR qRT PCR blot GANT61 GANT 5 1.4fold 14fold 1.4 1 4 P 0.01, 001 0.01 , 0 01 0.01) runtrelated runt related factor2 factor 2 factor- RUNX2. RUNX2 RUNX . (RUNX2) Furthermore 1.7fold 17fold 1.7 7 2.6fold 26fold 2.6 6 P<0.001. P0001 P<0.001 (P<0.001) lineage 3 1.3 13 1.6fold 16fold 1.6 inhibited P<0.01. P001 P<0.01 (P<0.01) applications Alginatefibrin Alginate trauma tumors extraction Additionally periodontitis GANT6 4fold 14 1. 00 0.0 (RUNX2 7fold 17 6fold 26 2. P000 P<0.00 (P<0.001 16 P00 P<0.0 (P<0.01 0. (RUNX (P<0.00 P0 P<0. (P<0.0 P<0 (P<0. P< (P<0 (P<

Abstract The segmentation of athlete knee joint injury images can provide doctors with information about the location and extent of the athlete knee joint injury. Therefore, it is significant to segment the images of athlete knee joint injury. However, the traditional image segmentation method of athlete knee injury has the problems of low accuracy of mask region extraction, completion time of extraction and high error rate of segmentation. In the paper, we propose image segmentation method for athlete knee joint injury using the transformer model by the medical Internet of Things (MIoT). First, the MIoT was used as a way to obtain images of knee joint injury of athletes, and the images of knee joint injury of athletes were derived using the MIoT. Second, the exported image is input into the shadow expansion layer of the transformer model, which performs shadow expansion on the athlete knee joint injury image to obtain its mask region, and then the image is input into the patch embedding layer. Finally, after the patch embedding layer extracts the mask patch of the athlete knee joint injury image, the mask patch is input into the transformer block for down-sampling and up-sampling processing, and then the athlete knee joint injury image segmentation result is output using the end backpropagation layer. The results show that the proposed method has a low error rate in extracting the mask region from the knee joint injury image of athletes, and a short completion time for extracting the mask region, the most detailed and comprehensive segmented athlete knee joint injury image, the maximum error rate of image segmentation is only 6.8%, and the maximum value of segmentation time is only 3.96s. It has important research value in the field of athlete knee joint injury diagnosis. Therefore However paper . (MIoT) First Second Finally downsampling down sampling upsampling up processing 68 6 8 6.8% 396s s 3 96s 3.96s diagnosis (MIoT 6.8 6.

Abstract In this paper, LS-dyna software was used to simulate the charging process of cylindrical shell when EFP has different angles, and some interesting phenomena and laws were found. Cylindrical elastic wave σr was generated when the cylindrical shell was impacted by EFP. The cylindrical elastic wave σr was correlated with the time required for the cylindrical shell charge to be successfully detonated. When the EFP warhead penetration Angle θ ranges from 0° to 10°, the σr increases linearly with (cosθ)-1/2. With the increase of θ, the tangential velocity vy had an obvious effect on the impact of EFP on the cylindrical shell, and the linear relationship between the elastic wave σr and (cosθ)-1/2 does not change. When the θ was greater than 45°, EFP could not successfully impact and detonate the cylindrical shell charge. The EFP velocity was measured by velocity measurement method with an error of 1.3%. The experimental results have strong similarity with the simulation results, indicating that the parameters of the numerical simulation model have good reliability.

Myocardial ischemia/reperfusion (MI/R) injury is a complex phenomenon that causes severe damage to the myocardium. However, the potential molecular mechanisms of MI/R injury have not been fully clarified. We identified potential molecular mechanisms and therapeutic targets in MI/R injury through analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found between MI/R injury and normal samples, and overlapping DEGs were found between GSE61592 and GSE67308. Gene Ontology (GO) and pathway analysis were performed for overlapping DEGs by Database for Annotation, Visualization and Integration Discovery (DAVID). Then, a network of protein-protein interaction (PPI) was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) database. Potential microRNAs (miRNAs) and therapeutic small molecules were screened out using microRNA.org database and the Comparative Toxicogenomics database (CTD), respectively. Finally, we identified 21 overlapping DEGs related to MI/R injury. These DEGs were significantly enriched in IL-17 signaling pathway, cytosolic DNA-sensing pathway, chemokine signaling, and cytokine-cytokine receptor interaction pathway. According to the degree in the PPI network, CCL2, LCN2, HP, CCL7, HMOX1, CCL4, and S100A8 were found to be hub genes. Furthermore, we identified potential miRNAs (miR-24-3p, miR-26b-5p, miR-2861, miR-217, miR-4251, and miR-124-3p) and therapeutic small molecules like ozone, troglitazone, rosiglitazone, and n-3 polyunsaturated fatty acids for MI/R injury. These results identified hub genes and potential small molecule drugs, which could contribute to the understanding of molecular mechanisms and treatment for MI/R injury.

The objective of this study was to explore the role of the SULF2-mediated ERK/AKT signaling pathway in cervical cancer. SULF2 expression was detected in tumor tissues and tumor-adjacent normal tissues from cervical cancer patients. HeLa cells were divided into six groups: control group, NC group, SULF2 siRNA group, SULF2 group, SULF2 + LY294002 group, and SULF2 + U0125 group. In each group, HeLa cells received the corresponding treatment, followed by measurement of the cellular biological characteristics and expression of the ERK/AKT signaling pathway. We also confirmed the effect of SULF2 in vivo using a xenograft model in nude mice. SULF2 was upregulated in cervical cancer tissues, which was specifically associated with the clinical stage, histological differentiation, and lymphatic metastasis. Compared to the control group, the SULF2 siRNA group displayed decreased expression of SULF2, concomitant with reduced proliferation, migration, and invasion, but there was an increase in the apoptosis rate of HeLa cells, as well as downregulation of the p-Akt/Akt, p-ERK/ERK, and Bax/Bcl-2 ratios and cyclin D1. Additionally, tumor growth was significantly inhibited in the xenograft model of nude mice. The results in the SULF2 group were quite the opposite in which SULF2 facilitated the growth of cervical cancer cells, which was reversed by LY294002 or U0126. SULF2 is highly expressed in cervical cancer, and thus, downregulation of SULF2 can inhibit the ERK1/2 and AKT signaling pathways to suppress the proliferation, invasion, and migration of cervical cancer cells while facilitating apoptosis.

Aortic dissection is characterized by the redirection of blood flow, which flows through an intimal tear into the aortic media. The purpose of this study was to find potential acute type A aortic dissection (AAAD)-related genes and molecular mechanisms by bioinformatics. The gene expression profiles of GSE52093 were obtained from Gene Expression Omnibus (GEO) database, including 7 AAAD samples and 5 normal samples. The differentially expressed genes (DEGs) were detected between AAAD and normal samples. The functional annotation and pathway enrichment analysis were conducted through the Database for Annotation, Visualization and Integration Discovery (DAVID). A protein-protein interaction network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) software. The microRNAs (miRNAs) of these differentially expressed genes were predicted using <microRNA.org> database. Moreover, DEGs were analyzed in the comparative toxicogenomics (CTD) database to screen out the potential therapeutic small molecules. As a result, there were 172 DEGs identified in patients with AAAD. These DEGs were significantly enriched in 6 pathways, including cell cycle, oocyte meiosis, DNA replication, extracellular matrix-receptor interaction, and mineral absorption pathway. Notably, CDC20, CDK1, CHEK1, KIF20A, MCM10, PBK, PTTG1, RACGAP, and TOP2A were crucial genes with a high degree in the protein-protein interaction network. Furthermore, potential miRNAs (miR-301, miR-302 family, and miR-130 family) were identified. In addition, small molecules like azathioprine and zoledronic acid were identified to be potential drugs for AAAD.

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

A compact CPW-fed ultra-wideband antenna with dual band-notch characteristic is presented. Two notched frequency bands are obtained by embedding two U-shaped slots in the radiation patch and a rectangle slot in the ground plane. The two notched bands can be controlled by adjusting the length of the responding slots. The proposed antenna is successfully simulated, fabricated and tested. Experimental and numerical antenna shows that the proposed antenna with compact size of 21×28mm2, has an impedance bandwidth range from 3.1GHz to more than 11.0GHz for voltage standing-wave ratio less than 2, expect two notch band frequency 5GHz-6GHz for WLAN and 7.7GHz-8.5GHz for X-band for satellite communications in China.

Batch tests were performed to investigate the nitrite effect on the P-uptake of biomass grown in pilot-scale SBR and MBR systems. The results showed that the nitrite has an inhibitory effect on the aerobic P-uptake of the SBR and the MBR biomasses. The degree of inhibition was observed to be 65 % and 37 % at 10 mg NO2-N/ℓ for the SBR and the MBR respectively. Both biomasses were found capable of using nitrite as electron acceptor as effectively as nitrate. Moreover, for the SBR biomass the anoxic P-uptake rate using nitrite was found even higher (60%) than the P-uptake rate with nitrate. From a modelling point of view, the current models require appropriate extensions to describe these various effects of nitrite. Hence, an extension of the ASM2d model has been provided. Prevention of nitrite build-up in full-scale EBPRs will eliminate the nitrite inhibition problem. Alternatively one can adopt a proactive approach in which the aerobic P-uptake phase is replaced with an anoxic P-uptake phase using only nitrite as electron acceptor. Such an approach offers considerable cost savings and enhanced nitrogen and phosphorus removal. This, however, requires further research for experimental validation and testing.