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Objective: To investigate whether miR-483-5p regulates osteoclast generation by targeting Timp2. miR-483-5p can promote osteoclast differentiation and bone destruction. Methods: Target genes of miR-483-5p were predicted by miRNAs target gene prediction software TargetScan8.0, and wild type and mutant 3' UTR plasmids were constructed. Dual luciferase reporter genes were used to verify whether target genes had a targeted regulatory relationship with miR-483-5p. Western blotting was used to detect the corresponding changes in the expression level of target protein after adjusting the level of miR-483-5p in cells. Cells were transfected or infected with target gene siRNA or target protein lentivirus, and TRAP staining and q-PCR assays were performed. In addition, for osteoclast induction experiment, RAW264.7 cells were co-transfected with ago-miR-483-5p and target protein-overexpressed lentiviruses q-PCR and TRAP staining were performed respectively. Results: Bioinformatics software was used to predict the target gene of miR-483-5p, and the Timp2 gene was found to regulate osteoclasts, and the dual luciferase reporter detection system found that miR-483- 5p could be associated with the 3-UTR of the predicted target gene Timp2 gene. There are complementary loci and targeted regulatory relationship between them. Subsequently, we upregulated miR-483-5p in RAW264.7 cells to reduce the expression of Timp2. Compared with the normal group, the number of osteoclasts and the expression of osteoclast-specific genes increased significantly after the induction of Timp2 in knockdown cells. After co-transfection of target gene and miR-483-5p into cells, the number of osteoclasts and the expression of specific genes decreased significantly compared with the normal group. Conclusion: Timp2 is a downstream target gene of miR-483-5p and is involved in and inhibits osteoclast generation. [ABSTRACT FROM AUTHOR]

Airway epithelial cells, the first barrier of the respiratory tract, play an indispensable role in innate immunity. Integrin β4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases and is downregulated in asthmatic patients. Research has shown that endothelial ITGB4 has proinflammatory properties in acute lung injury (ALI). However, the role of epithelial ITGB4 in a murine ALI model is still unknown. This study investigated the role of ITGB4 in lipopolysaccharide (LPS)‐induced ALI. We found that ITGB4 in the airway epithelium had remarkably increased after the introduction of LPS in vivo and in vitro. Then, we constructed airway epithelial cell‐specific ITGB4 knockout (ITGB4−/−) mice to study its role in ALI. At a time point of 12 h after the tracheal injection of LPS, ITGB4−/− mice showed increased macrophages (mainly M1‐type macrophages) and neutrophil infiltration into the lungs; inflammation‐related proteins including interleukin (IL)‐6, tumor necrosis factor, and IL‐17A were significantly elevated compared to their levels in ITGB4+/+ mice. Furthermore, we investigated the role of ITGB4 in the anti‐inflammatory response. Intriguingly, in the ITGB4−/− + LPS group, we found significantly reduced expression of anti‐inflammatory factors, including IL‐10 messenger RNA (mRNA) and ARG‐1 mRNA. We also observed that monocyte chemotactic protein (MCP‐1) increased significantly both in vivo and in vitro. Airway epithelium activates macrophages, most likely driven by MCP‐1, which we confirmed in the coculture of epithelia and macrophages. These phenomena indicate that ITGB4 in airway epithelial cells plays an important role in the process of inflammation and activation of macrophages in ALI. Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in LPS‐induced ALI. [ABSTRACT FROM AUTHOR]

In inter-satellite laser communication, four-quadrant detector is often used in precise tracking unit for spot location. The positioning error directly affects the angular measurement accuracy of fine tracking unit. In order to achieve the tracking precision of micro-radian magnitude, this paper studies various noise factors that affect the positioning accuracy of the detector, simplifying the analysis according to the practice of inter-satellite laser communication, and putting forward the specific calculation method of positioning error. Finally, we evaluate the influence degree of each factor through a specific example. The results show that the signal-to-noise ratio of the received signal increases with the increasing of emitting power in a certain range with reduced positioning error. However, positioning error does not decrease linearly with the increase of transmitting power. When the transmitting power increases to a certain extent, the reduction of tracking error is limited. At this time, it will be very expensive to improve the tracking precision simply by increasing the transmitting power. [ABSTRACT FROM AUTHOR]

A flexible dicarboxylic acid, 4,4'-{[1,3-phenylenebis-(methylene)]bis(oxy) dibenzoic acid (H 2 L), in combination with 1,10-phenanthroline (phen) was used to reacted with Zn(II) ions under hydrothermal conditions, successfully affording a new metal-organic framework of [Zn(L)(phen)(H 2 O)] n (1). Luminescence sensing property investigations indicate that, compound 1 is sensitive detector of Fe3+ ions based on quenching of luminescence. Its treatment activity on the child allergic purpura was assessed and the specific mechanism of the compound was explored at the same time. First of all, the content of the inflammatory cytokine released into the skin tissue was measured with ELISA detection kit after the compound treatment. Apart from this, the activation ability of the AMPK inflammatory signaling pathway was measured with real time RT-PCR. [Display omitted] • A new Zn(II)-based compound has been prepared. • It can be used as a sensor for Fe3+ ​ion. • It has the potential choice for the allergic purpura therapy. [ABSTRACT FROM AUTHOR]

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.

Preeclampsia (PE) is an important topic in obstetrics. In this study, we used weighted gene co-expression network analysis (WGCNA) to screen the key modules related to immune cell infiltration and to identify the hub genes for the molecular subtyping of PE. We first downloaded a set of PE transcriptional data (GSE75010; 157 samples: 80 PE and 77 non-PE) from the GEO database. We then analyzed the PE samples and non-PE samples for immune cell infiltration and screened cells with differences in such infiltration. Next, we downloaded the immune-related genes from an immune-related database to screen the expression profile of the immune-related genes. Then, we obtained a candidate gene set by screening the immune-related genes differentially expressed between the two groups. We used WGCNA to construct a weighted co-expression network for these candidate genes, mined co-expression modules, and then calculated the correlation between each module and immune cells with differential infiltration. We screened the modules related to infiltrating immune cells, identified the key modules' hub genes, and determined the key module genes that interacted with each other. Finally, we obtained the hub genes related to the infiltrating immune cells. We classified the preeclampsia patients by unsupervised cluster molecular typing, determined the difference of immune cell infiltration among the different PE subtypes, and calculated the expression of hub genes in these different subtypes. In conclusion, we found 41 hub genes that may be closely related to the molecular typing of PE.

Lung cancer is one of the most common malignant neoplasms worldwide. CD24 is a marker of tumor stem cells that plays an important role in tumorigenesis. Hsp70 is an important molecular chaperone. However, the co-expression and interaction of CD24 and Hsp70, as well as the significance for the prognosis of lung cancer are still unclear. The expression levels of CD24 and Hsp70 were detected by immunohistochemistry and their correlation was analyzed. The expression levels of CD24 mRNA and protein were examined using qRT-PCR and western blotting in SPCA1, A549, H1975, and H1650 cell lines. A CD24-overexpressing cell model was established. The interaction between CD24 and Hsp70 was verified by co-immunoprecipitation and western blotting. CD24 and Hsp70 expression were significantly higher in lung cancer tissues than in adjacent tissues (CD24: p=0.008; Hsp70: p<0.001). CD24 protein expression showed a positive correlation with lymph node metastasis, TNM stage, and vascular cancer thrombus. Hsp70 protein expression showed a positive correlation with differentiation, lymph node metastasis, and TNM stage. CD24 and Hsp70 high expression were also correlated with poor survival. The positive co-expression rate of CD24 and Hsp70 in lung cancer tissues was 52.7% (49/93). CD24 and Hsp70 expression in lung cancer were positively correlated (r=0.368, p<0.001), and co-immunoprecipitation was verified that both endogenous and exogenous CD24 co-precipitated with Hsp70 directly or indirectly. When Hsp70 inhibitor VER15508 was added to A549 cells, Hsp70 and CD24 protein expression were significantly decreased. The present study demonstrated that CD24 and Hsp70 were highly expressed in lung cancer tissues, and associated with invasion, metastasis, and poor survival. Hsp70 may regulate CD24 expression. Co-expression of CD24 and Hsp70 may be a prognostic biomarker for lung cancer.

Objective: To compare the clinical manifestations of pertussis in children of different ages and different immunization statuses in Wenzhou, and to explore the limitations of diagnostic criteria for pertussis., Methods: The clinical data of 288 children diagnosed with pertussis at Yuying Children's Hospital & the Second Affiliated Hospital of Wenzhou Medical University from October 2017 to December 2019 were retrospectively analyzed. The clinical characteristics of children of different ages and different immunization statuses were analyzed. Their clinical data were compared to relevant diagnostic criteria of pertussis in children of different ages according to the Recommendations for Diagnosis and Treatment of Chinese Children with Pertussis and the diagnosis conformity rate was analyzed., Results: Among the 288 children, 124 cases (43.06%) were 3 months old or younger, and 164 cases (288, 56.94%) were >3 months old. Among patients≤3 months of age, cyanosis, three-depression sign, face redness, dyspnea and peripheral blood lymphocyte ratio were significantly higher than those of patients >3 months of age. They also had higher incidence of pneumonia, higher proportion of developing severe pertussis, and longer stay at the hospital. All these findings showed statistically significant difference ( P <0.05). 83 children were fully immunized (receiving the full course of vaccination), and 205 were not fully immunized (not receiving the full course of vaccination or being unvaccinated). The proportion of children presenting cyanosis, shortness of breath, three depression sign and face redness in the incomplete immunization group was higher than that in the complete immunization group. In the incomplete immunization group, the proportion of lymphocytes was higher, the level of C-reactive protein (CRP) was lower, and the length of hospitalization was longer than those of the complete immunization group. All the differences were statistically significant ( P <0.05). Among patients aged ≤3 months, the conformity rate of diagnosis (112/114, 90.32%) upon admission was higher than that among patients aged >3 months (119/164, 72.56%). Among patients aged ≤3 months, 41.94% (52/124, while 54.03% (67/124) of the patients aged ≤3 months had WBC count <20×10 9 L -1 ., Conclusion: Pertussis in children ≤3 months of age in Wenzhou City were more serious, showing higher rate of diagnosis conforming to the recommended clinical diagnostic criteria than that in children >3 months old. The WBC threshold in routine blood test of ≤3 months old could be lowered appropriately and the current diagnostic criteria still needed improvement., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)