This study aims to evaluate the effects of cold atmospheric plasma (CAP) treatment on the bonding of resin cement to high-translucency zirconia. Zirconia specimens were subjected to different ...treatments: no treatment (ZrT), 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primer (ZrT-M), alumina particle air-abrasion with/without MDP-containing primer (ZrT-AM/ZrT-A), CAP with/without MDP-containing primer (ZrT-PM/ZrT-P). The surface topography, wettability, and chemical composition were evaluated. The shear bond strength (SBS) was tested before and after thermocycling. CAP did not alter the morphology, increased the wettability, and decreased the carbon/oxygen ratio of zirconia surface. The SBSs of ZrT-PM and ZrT-P were significantly higher than the other groups. After thermocycling, ZrT-A, ZrT-M, ZrT-AM, and ZrT-P showed comparable SBSs, all of which were lower than ZrT-PM. It was concluded that CAP improved the bonding performance of high-translucency zirconia without damaging its surface. The combination of CAP with MDP further enhanced the bond strength and may enable durable bonding.
Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases ...has not been fully examined.
The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%), 70% (95% CI 15%-89%), and 69% (95% CI 34%-85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%). Receiving a booster at age 10-14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio HR = 0.68, 95% CI 0.47-0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up.
Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors' Summary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The principal aim of this investigation is to identify pivotal biomarkers linked to the prognosis of osteosarcoma (OS) through the application of artificial intelligence (AI), with an ultimate goal ...to enhance prognostic prediction. Expression profiles from 88 OS cases and 396 normal samples were procured from accessible public databases. Prognostic models were established using univariate COX regression analysis and an array of AI methodologies including the XGB method, RF method, GLM method, SVM method, and LASSO regression analysis. Multivariate COX regression analysis was also employed. Immune cell variations in OS were examined using the CIBERSORT software, and a differential analysis was conducted. Routine blood data from 20,679 normal samples and 437 OS cases were analyzed to validate lymphocyte disparity. Histological assessments of the study's postulates were performed through immunohistochemistry and hematoxylin and eosin (HE) staining. AI facilitated the identification of differentially expressed genes, which were utilized to construct a prognostic model. This model discerned that the survival rate in the high-risk category was significantly inferior compared to the low-risk cohort (p < 0.05). SERPINE2 was found to be positively associated with memory B cells, while CPT1B correlated positively with CD8 T cells. Immunohistochemical assessments indicated that SERPINE2 was more prominently expressed in OS tissues relative to adjacent non-tumorous tissues. Conversely, CPT1B expression was elevated in the adjacent non-tumorous tissues compared to OS tissues. Lymphocyte counts from routine blood evaluations exhibited marked differences between normal and OS groups (p < 0.001). The study highlights SERPINE2 and CPT1B as crucial biomarkers for OS prognosis and suggests that dysregulation of lymphocytes plays a significant role in OS pathogenesis. Both SERPINE2 and CPT1B have potential utility as prognostic biomarkers for OS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
At present, the impact of cuproptosis-related genes in the study of osteosarcoma is largely unknown. Genome-wide data of osteosarcoma and controls were downloaded from 3 different databases, and ...specific diagnostic models associated with cuproptosis in osteosarcoma were constructed by support vector machines with artificial intelligence, random forest trees and LASSO regression. Differential analysis of immune cell infiltration was examined using routine blood data from 25,665 cases. Differential expression was examined using immunohistochemistry and PCR. PDHA1 and CDKN2A were obtained as specific cuproptosis-related biomarkers for osteosarcoma after artificial intelligence analysis. PDHA1, CDKN2A and neutrophils were differentially expressed in OS and control groups. PDHA1 and CDKN2A are significantly dysregulated in OS and are able to serve as biomarkers of OS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Old livers are more damaged by hepatic ischemia and reperfusion (IR) injury than young livers. The aim of this study was to investigate the effects of ischemic and rapamycin preconditioning on IR ...injury in old livers. Young (8-week-old) and aged (60-week-old) mice were subjected to IR or a sham control procedure. The aged mice were randomly divided into six groups: IR (CON), IR with ischemic preconditioning (IPC), IR with rapamycin preconditioning (RAPA), IR with combined ischemic and rapamycin preconditioning (IPC + RAPA), IR with 3-methyladenine (3-MA), IR with combined ischemic and rapamycin preconditioning with 3-MA pretreatment (IPC + RAPA+3-MA). Liver injury was evaluated 6 h after reperfusion. Hepatocellular autophagy induction was also analyzed by western blotting. The results revealed that aged mice had aggravated liver IR injury as compared to young mice. In aged mice following IR, IPC + RAPA but not IPC or RAPA alleviated liver injury, as evidenced by lower levels of serum ALT, improved preservation of liver architecture with lower Suzuki scores, and decreased caspase-3 activity compared with CON. In addition, western blot analysis revealed increased LC3B II but decreased p62 protein expression levels in the IPC + RAPA group, indicating that autophagic flux was restored by combined ischemic and rapamycin preconditioning. Furthermore, autophagy inhibition by the inhibitor 3-MA abrogated the protective role in the IPC + RAPA group, while no significant effects were observed in the CON group. In conclusions, our results demonstrated that combined ischemic and rapamycin preconditioning protected old livers against IR injury, which was likely attributed to restored autophagy activation.
•Aging aggravated liver IR injury.•Combined but not separate IPC and RAPA treatment protected old livers against IR•Combined IPC and RAPA treatment restored autophagy activation in old livers post IR
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fever is an evolutionarily conserved response that confers survival benefits during infection. However, the underlying mechanism remains obscure. Here, we report that fever promoted T lymphocyte ...trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to α4 integrins, but not β2 integrins, fever increased α4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the α4 tail and activated α4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two α4 tails, leading to dimerization and clustering of α4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-α4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-α4-integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.
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•Fever promotes α4-integrin-mediated T cell adhesion and transmigration•Hsp90 binds to α4 tails and activates α4 integrins via inside-out signaling•Hsp90 triggers dimerization and clustering of α4 integrins to activate FAK-RhoA•Disruption of Hsp90-α4 interaction impairs fever-induced T cell trafficking
Fever is an evolutionarily conserved response in both endothermic and ectothermic species and confers survival benefits during infection and injury. Lin et al. identify that the Hsp90-α4-integrin axis serves as a thermal sensory pathway that responds to fever to promote T cell trafficking and enhance immune surveillance during infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genome editing by the well-established CRISPR/Cas9 technology has greatly facilitated our understanding of many biological processes. However, a complete whole-genome knockout for any species or ...model organism has rarely been achieved. Here, we performed a systematic knockout of all the genes (1333) on Chromosome 1 in zebrafish, successfully mutated 1029 genes, and generated 1039 germline-transmissible alleles corresponding to 636 genes. Meanwhile, by high-throughput bioinformatics analysis, we found that sequence features play pivotal roles in effective gRNA targeting at specific genes of interest, while the success rate of gene targeting positively correlates with GC content of the target sites. Moreover, we found that nearly one-fourth of all mutants are related to human diseases, and several representative CRISPR/Cas9-generated mutants are described here. Furthermore, we tried to identify the underlying mechanisms leading to distinct phenotypes between genetic mutants and antisense morpholino-mediated knockdown embryos. Altogether, this work has generated the first chromosome-wide collection of zebrafish genetic mutants by the CRISPR/Cas9 technology, which will serve as a valuable resource for the community, and our bioinformatics analysis also provides some useful guidance to design gene-specific gRNAs for successful gene editing.
Diacylglycerol acyltransferase（DGAT） plays an important role in plant oil metabolism and stress resistance. To explore the evolution of DGAT gene in sunflower（Helianthus annuus L.） and its function ...in oil biosynthesis and response to abiotic stresses, 18 homologous gene sequences of DGAT were obtained from the sunflower genome database by alignment with Arabidopsis thaliana At DGATs genes. Then, chromosome distribution, gene structure, conserved protein motifs, phylogenetic relationship, tissue-specific expression of Ha DGATs, and their expressing patterns under abiotic stresses were systematically investigated. The results showed that sunflower DGATs genes were divided into four subfamilies（DGAT1, DGAT2, DGAT3, and WSD）,and the members of the same subfamily shared similar gene structures and conserved motifs. The promoter regions of Ha DGATs harbored multiple cis-elements related to environmental stresses and plant hormone response. The main factor for Ha DGATs amplification was fragment duplication. The qRT
Our previous study demonstrated that preoperative short-term fasting attenuates mice hepatic ischemia/reperfusion injury (IRI), which greatly piqued our interest in verifying if fasting produces ...similar protective effects in patients undergoing hepatectomy.
Eighty patients with liver tumors were randomized into control (Ctrl, n=40, preoperative fasting for 6 h) or fasting group (Fasting, n=40, preoperative fasting for 24 h). Serum was collected at pre-operation (Pre-Op), post-operation 1 day (POD-1), post-operation 3 days (POD-3), and post-operation 7 days (POD-7). Liver tissue was removed from the resected specimen.
Sixty-three patients were eventually enrolled, with 33 in Ctrl and 30 in Fasting group. Our data showed that 24 h fasting effectively attenuated elevated sALT and sAST levels after operation (P<0.05), but serum total bilirubin was significantly lower at only POD-3 (P<0.05); and serum albumin was not markedly different in either of the groups. Interestingly, 24 h fasting partially attenuates expression of pro-inflammatory cytokine (TNF-α) and improves oxidative stress (MDA and SOD). Our data further showed short-term fasting triggered Nrf2 signaling pathway.
This study demonstrates preoperative short-term fasting effectively improves clinical outcomes and markedly attenuates inflammatory responses and oxidative stress in patients undergoing hepatectomy, and Nrf2 signaling pathway may play a key role in fasting against inflammatory responses and oxidant stress.
This study aims to evaluate the effects of cold atmospheric plasma (CAP) treatment on the bonding of resin cement to high-translucency zirconia. Zirconia specimens were subjected to different ...treatments: no treatment (ZrT), 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primer (ZrT-M), alumina particle air-abrasion with/without MDP-containing primer (ZrT-AM/ZrT-A), CAP with/without MDP-containing primer (ZrT-PM/ZrT-P). The surface topography, wettability, and chemical composition were evaluated. The shear bond strength (SBS) was tested before and after thermocycling. CAP did not alter the morphology, increased the wettability, and decreased the carbon/oxygen ratio of zirconia surface. The SBSs of ZrT-PM and ZrT-P were significantly higher than the other groups. After thermocycling, ZrT-A, ZrT-M, ZrT-AM, and ZrT-P showed comparable SBSs, all of which were lower than ZrT-PM. It was concluded that CAP improved the bonding performance of high-translucency zirconia without damaging its surface. The combination of CAP with MDP further enhanced the bond strength and may enable durable bonding.
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