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Zirconia nanoparticles (NPs) have been widely used in biomedicine, which will likely lead to their interactions with endothelial cells (ECs). However, the toxicity of zirconia NPs to ECs is less investigated and the toxicological data are not consistent. Furthermore, no previous study, to the best of our knowledge, investigated the influence of zirconia NPs on lipid metabolism. This study investigated lipid profiles in human umbilical vein ECs (HUVECs) exposed to zirconia NPs with or without the presence of free fatty acids (FFAs). Incubation with FFA changed the hydrodynamic size, zeta potential, and surface profiles of zirconia NPs, indicating the surface coating effects. Exposure of HUVECs to various concentrations of zirconia NPs with or without the presence of FFA did not significantly decrease cellular viability, but FFA decreased zirconium elemental levels in NP‐exposed cells. Oil Red O staining showed that FFA or zirconia NPs and FFA, but not zirconia NPs alone, significantly increased lipid accumulation in HUVECs. Consistently, lipidomic data suggested that exposure to FFA or zirconia NPs and FFA up‐regulated most lipid classes in HUVECs. As the mechanisms for increased lipid accumulation, exposure to FFA or zirconia NPs and FFA up‐regulated endoplasmic reticulum (ER) stress axis IRE1α–XBP‐1, leading to increased FASN and ACSL3, proteins involved in lipid metabolism. Combined, our results demonstrated that zirconia NPs were noncytotoxic and showed minimal impact on ER stress‐mediated lipid metabolism in HUVECs under both normal and FFA‐challenged conditions, which indicated the relatively high biocompatibility of zirconia NPs to ECs. This study investigated the changes of lipid profiles in HUVECs after exposure to zirconia NPs with or without the presence of FFA. FFA was coated onto zirconia NPs and decreased NP internalization. Exposure to zirconia NPs did not decrease cellular viability. Exposure to FFA or zirconia NPs and FFA increased lipid accumulation and most lipid classes in HUVECs due to up‐regulated IRE1α–XBP‐1 axis leading to increased FASN and ACSL3. These results indicated relatively high biocompatibility of zirconia NPs to HUVECs. [ABSTRACT FROM AUTHOR]

Abstract: SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21‐1), and neuron‐specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression‐free survival (PFS) were analyzed. Serum SP70 levels were significantly decreased after chemotherapy in the partial remission (PR) group (P < .001) and increased in the progressive disease (PD) group (P < .001), but not significantly changed in the stable disease (SD) group (P = .114). Although similar changes were observed on CEA and CYFRA21‐1 levels but not NSE, ROC analysis demonstrated that SP70 is superior to the others. Additionally, patients with EGFR mutation had higher serum SP70 levels and tissue SP70 expression than patients without EGFR mutation (P = .014 and P = .002, respectively). The median PFS of patients with decreased SP70 levels after chemotherapy was longer than that of patients with stable or increased serum SP70 level (24 months vs 12 months vs 2 months, P < .001), and the differences of all other 3 tumor markers were not obvious. Serum SP70 is a sensitive and real‐time indicator of chemotherapeutic efficacy in patients with advanced NSCLC and related to PFS. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus warneri is an opportunistic pathogen responsible for hospital-acquired infections (HAIs). The aim of this study was to describe an outbreak caused by S. warneri infection in a neonatal intensive care unit (NICU) and provide investigation, prevention and control strategies for this outbreak., Methods: We conducted an epidemiological investigation of the NICU S. warneri outbreak, involving seven neonates, staff, and environmental screening, to identify the source of infection. WGS analyses were performed on S. warneri isolates, including species identification, core genome single-nucleotide polymorphism (cgSNP) analysis, pan-genome analysis, and genetic characterization assessment of the prevalence of specific antibiotic resistance and virulence genes., Results: Eight S. warneri strains were isolated from this outbreak, with seven from neonates and one from environment. Six clinical cases within three days in 2021 were linked to one strain isolated from environmental samples; isolates varied by 0-69 SNPs and were confirmed to be from an outbreak through WGS. Multiple infection prevention measures were implemented, including comprehensive environmental disinfection and stringent protocols, and all affected neonates were transferred to the isolation wards. Following these interventions, no further cases of S. warneri infections were observed. Furthermore, pan-genome analysis results suggested that in human S. warneri may exhibit host specificity., Conclusion: The investigation has revealed that the outbreak was linked to the milk preparation workbench by the WGS. It is recommended that there be a stronger focus on environmental disinfection management in order to raise awareness, improve identification, and prevention of healthcare-associated infections that are associated with the hospital environment., Competing Interests: The authors report no conflicts of interest in this work, (© 2024 Zhang et al.)

Background: The purpose of the investigation was to assess the value of post-operation platelet to creatinine ratio (PCR) in predicting in-hospital mortality among patients with acute type A aortic dissection (TAAAD)., Methods: A retrospective study was carried out from January 2017 to December 2019. The best cutoff value of post-operation PCR was assessed by receiver operating characteristic (ROC) curve. Patients were divided into survivors and nonsurvivors. Univariate and multivariate logistic analyses were carried out to identify independent risk factors influencing in-hospital mortality., Results: A total of 171 patients were included in this investigation, with an in-hospital mortality rate of 18.1%. The optimal cut-off value of post-operation PCR was 0.7242 (area under the ROC curve (AUC): 0.798, 95% confidence interval (CI) 0.730-0.856, p < 0.001), and the sensitivity and specificity were 74.2% and 74.3%. The levels of post-operation PCR were lower in nonsurvivors than in survivors (0.56 ± 0.33 vs. 1.50 ± 1.36, p < 0.001). Multivariate logistic regression analysis displayed that post-operation PCR was positively related to in-hospital survivors when confounding factors were adjusted (HR = 8.850, 95% CI = 2.611-30.303, p < 0.001)., Conclusions: Post-operative PCR is a readily accessible and cost-effective biomarker that is independently associated with in-hospital mortality in TAAAD patients. Furthermore, it exhibits superior performance in predicting patient outcomes following surgery.

This experimental study was aimed to construct the recombinant adenovirus vector containing human GDF-5 gene, and to use it for infecting human MSCs and detecting the expression of the gene GDF-5. The core sequence of human GDF-5 was amplified by PCR from pCMV-SPORT6, and then was cloned to pAdtrack-CMV. The linearized shuttle plasmid pAdtrack-CMV-GDF-5 was homogenously recombined with pAdeasy-1 in BJ5183. The potential clone was analyzed by restriction endonuclease digestion. The correct clone was linearized and transfected into QBI-293 cells for packing and amplifying so as to obtain adenovirus pAd-GDF-5 and identify it, while the titer was also determined by TCID50. MSCs were infected by the harvested virus, and the expression of GDF-5 was detected by RT-PCR. The recombinant adenovirus vector containing human GDF-5 gene was constructed successfully, its titer was 1 x 10(9) PFU/ml, and it could infect MSCs efficiently. The human MSCs infected by constructed adenovirus vector could continue expressing GDF-5 in a certain time, and the transgenic MSCs would be much potential on tissue regeneration.

Objective: To introduce growth and differentiation factor 5 (GDF-5) gene into hBMSCs using recombinant adenovirus vector and to investigate the effect of GDF-5 gene expression on hBMSCs osteogenic differentiation., Methods: Recombinant adenovirus GDF-5 (Ad-GDF-5) containing green fluorescent protein (GFP) and Ad-GFP were amplified and titered. hBMSCs at passage 3 were infected with two viruses at different titers. At 2 days after intervention, GFP expression was observed using fluorescence microscope, and GDF-5 expression in hBMSCs was detected by RT-PCR. Adherent hBMSCs at passage 3 were randomly divided into 4 groups: experimental group (GDF-5 gene transfection), osteogenic induction group, Ad-GFP infection group, and control group. Cell differentiation was detected by inverted phase contrast microscope observation, fluorescence microscope observation, reverse transcription fluorescence quantitative PCR, immunofluorescence staining, and von Kossa staining at different time points after intervention., Results: The titer of Ad-GDF-5 and Ad-GFP was 1.0 x 10(9) pfu/mL and 1.2 x 10(9) pfu/mL, respectively, hBMSCs was efficiently infected by Ad-GDF-5 and Ad-GFP, and expressed target gene and GFP gene. At 1-7 days after intervention, morphology and growth pattern of the hBMSCs in the experimental group and the osteogenic induction group were transformed into osteoblast-like cells, whereas the cells in the other two groups were still maintained their original morphology and growth pattern. Reverse transcription fluorescence quantitative PCR detection: at 4 days after intervention, GDF-5 expression in the experimental group was obviously higher than that of other groups (P < 0.05); ALP, Col I, and OC gene expression in the experimental and the osteogenic induction group were superior to those of the Ad-GFP infection and the control group (P < 0.05); Col I gene expression in the osteogenic induction group was greater than that of the experimental group (P < 0.05). Immunofluorescence staining: at 4 days after intervention, the cells in the osteogenic induction group and the experimental group expressed and secreted Col I, and no expression of Col I was evident in the other two groups. At 10 days after intervention, the cells in the osteogenic induction and the experimental group were positive for von Kossa staining, and the results of the other two groups were negative., Conclusion: GDF-5 gene can be transferred into hBMSCs via adenovirus vector and be expressed stably. It can facilitate the osteogenic differentiation of the hBMSCs and lay a foundation for the further study of this kind of gene transferred hBMSCs effect on bone tissue repair.