Interfacial toughness of the nickel-nickel oxide system

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Proteomic analysis of immediate-early response plasma proteins after 70% and 90% partial hepatectomy

AIM: Partial hepatectomy (PH) induces robust hepatic regenerative and metabolic responses that are considered to be triggered by humoral factors. The aim of the study was to identify plasma protein factors that potentially trigger or reflect the body's immediate-early responses to liver mass reduction. METHODS: Male C57BL/6 mice were subjected to sham operation, 70% PH or 90% PH. Blood was collected from the inferior vena cava at 20, 60 and 180 min after surgery. RESULTS: Using a label-free quantitative mass spectrometry-based proteomics approach, we identified 399 proteins exhibiting significant changes in plasma expression between any two groups. Of the 399 proteins, 167 proteins had multiple unique sequences and high peptide ID confidence (>90%) and were defined as priority 1 proteins. A group of plasma proteins largely associated with metabolism is enriched after 70% PH. Among the plasma proteins that respond to 90% PH are a dominant group of proteins that are also associated with metabolism and one known cytokine (platelet factor 4). Ninety percent PH and 70% PH induces similar changes in plasma protein profile. CONCLUSION: Our findings enable us to gain insight into the immediate-early response of plasma proteins to liver mass loss. Our data support the notion that increased metabolic demands of the body after massive liver mass loss may function as a sensor that calibrates hepatic regenerative response

Overexpression of candidate tumor suppressor ECRG4 inhibits glioma proliferation and invasion

<p>Abstract</p> <p>Background</p> <p>ECRG4 has been shown to be a candidate tumor suppressor in several tumors, but its role in glioma remains poorly understood. In this study, we examined the mRNA expression of ECRG4 and investigated its biological role in glioma cells.</p> <p>Methods</p> <p>Real-time PCR was used to examine expression of ECRG4 in gliomas and their matched brain tissues. The effect of ECRG4 expression on cell proliferation, invasion, and migration was investigated in human U251 glioma cells. Finally, the regulation of transcription factor NF-kB by ECRG4 was evaluated by western blotting.</p> <p>Results</p> <p>Of the 10 paired samples analyzed, 9 glioma tissues displayed the decreased expression of ECRG4 compared to matched normal brain tissues. Cells transfected with ECRG4 showed significantly decreased cell proliferation as evaluated by MTT and colony formation assays. Furthermore, overexpression inhibited cell migration and invasion in transwell and Boyden chamber experiments and retarded the cell cycle progression from G1 to S phase by FACSCaliber cytometry. Protein levels of nuclear transcription factor NF-kB, which is involved in cell proliferation, inversely correlated with ECRG4 expression.</p> <p>Conclusion</p> <p>Our data suggest that ECRG4 serves as a tumor suppressor in glioma.</p

Maternal hepatic growth response to pregnancy in the mouse

Pregnancy is characterized by physiological adjustments in the maternal compartment. In this investigation, the influence of pregnancy on maternal liver was examined in CD-1 mice. Dramatic changes were observed in the size of the maternal liver during pregnancy. Livers doubled in weight from the non-pregnant state to day 18 of pregnancy. The pregnancy-induced hepatomegaly was a physiological event of liver growth confirmed by DNA content increase and detection of hepatocyte hyperplasia and hypertrophy. Growth of the liver was initiated following implantation and peaked at parturition. The expression and/or activities of key genes known to regulate liver regeneration, a phenomenon of liver growth compensatory to liver mass loss, were investigated. The results showed that pregnancy-dependent liver growth was associated with interleukin (IL)-6, tumor necrosis factor α, c-Jun and IL-1β, but independent of hepatocyte growth factor, fibroblast growth factor 1, tumor necrosis factor receptor 1, constitutive androstane receptor and pregnane X receptor. Furthermore, maternal liver growth was associated with the activation of hepatic signal transducer and activator of transcription 3, β-catenin and epidermal growth factor receptor, but pregnancy did not activate hepatic c-Met. The findings suggest that the molecular mechanisms regulating pregnancy-induced liver growth and injury-induced liver regeneration exhibit overlapping features but are not identical. In summary, the liver of the mouse adapts to the demands of pregnancy via a dramatic growth response driven by hepatocyte proliferation and size increase

Nrf2 is essential for timely M phase entry of replicating hepatocytes during liver regeneration

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates various cellular activities, including redox balance, detoxification, metabolism, autophagy, proliferation, and apoptosis. Several studies have demonstrated that Nrf2 regulates hepatocyte proliferation during liver regeneration. The aim of this study was to investigate how Nrf2 modulates the cell cycle of replicating hepatocytes in regenerating livers. Wild-type and Nrf2 null mice were subjected to 2/3 partial hepatectomy (PH) and killed at multiple time points for various analyses. Nrf2 null mice exhibited delayed liver regrowth, although the lost liver mass was eventually restored 7 days after PH. Nrf2 deficiency did not affect the number of hepatocytes entering the cell cycle but did delay hepatocyte mitosis. Mechanistically, the lack of Nrf2 resulted in increased mRNA and protein levels of hepatic cyclin A2 when the remaining hepatocytes were replicating in response to PH. Moreover, Nrf2 deficiency in regenerating livers caused dysregulation of Wee1, Cdc2, and cyclin B1 mRNA and protein expression, leading to decreased Cdc2 activity. Thus, Nrf2 is required for timely M phase entry of replicating hepatocytes by ensuring proper regulation of cyclin A2 and the Wee1/Cdc2/cyclin B1 pathway during liver regeneration

PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women:a prospective cohort study

BackgroundImplementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women.MethodsA total of 3251 hrHPV-positive women aged 30–82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated.ResultsCerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 −) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%).ConclusionsPCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals.Trial registrationChiCTR2100048972. Registered on 19 July 2021.<br/

Preliminary study of improving immune tolerance in vivo of bioprosthetic heart valves through a novel antigenic removal method

The durability of bioprosthetic heart valves is always compromised by the inherent antigenicity of biomaterials. Decellularization has been a promising approach to reducing the immunogenicity of biological valves. However, current methods are insufficient in eliminating all immunogenicity from the biomaterials, necessitating the exploration of novel techniques. In this study, we investigated using a novel detergent, fatty alcohol polyoxyethylene ether sodium sulfate (AES), to remove antigens from bovine pericardium. Our results demonstrated that AES treatment achieved a higher pericardial antigen removal rate than traditional detergent treatments while preserving the mechanical properties and biocompatibility of the biomaterials. Moreover, we observed excellent immune tolerance in the in vivo rat model. Overall, our findings suggest that AES treatment is a promising method for preparing biological valves with ideal clinical application prospects

Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization

ObjectivesOur aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.MethodsWe extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.ResultsTwo taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.ConclusionsGut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases

Mink is a highly susceptible host species to circulating human and avian influenza viruses

Pandemic influenza, typically caused by reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remain unclear. In this study, we conducted serological surveys for avian and human influenza virus infections in farmed mink and determined the susceptibility of mink to prevailing avian and human virus subtypes. The results showed that farmed mink were commonly infected with human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Correlational analysis indicated that transmission of human influenza viruses occurred from humans to mink, and that feed source was a probable route of avian influenza virus transmission to farmed mink. Animal experiments showed that mink were susceptible and permissive to circulating avian and human influenza viruses, and that human influenza viruses (H3N2 and H1N1/pdm), but not avian viruses, were capable of aerosol transmission among mink. These results indicate that farmed mink could be highly permissive “mixing vessels” for the reassortment of circulating human and avian influenza viruses. Therefore, to reduce the risk of emergence of novel pandemic viruses, feeding mink with raw poultry by-products should not be permitted, and epidemiological surveillance of influenza viruses in mink farms should be urgently implemented