Experimental Study on the Strength and Damage Characteristics of Cement–Fly Ash–Slag–Gangue Cemented Backfill

publishedVersio

Risk of malignancy following exposure to Epstein-Barr Virus associated infectious mononucleosis: A nationwide population-based cohort study

PurposeEpstein-Barr virus (EBV) infection has been shown to contribute to oncogenesis and often causes acute clinical manifestation of Infectious mononucleosis (IM). It is unknown whether IM could increase the risk of subsequent malignancies. We aimed to evaluate the association of IM caused by EBV (EBV-IM) with overall and subtypes of malignancy in a large population-based cohort study.MethodsThis study included 1,419,407 individuals born in Denmark between 1973 and 2016 identified from national registers and 23,057 individuals had IM. The 5,394 of them had confirmed EBV-IM and they were birth date- and sex- matched (1:63) to 1,396,350 non-IM individuals. Cox regression was used to examine the associations of EBV-IM with malignancy.ResultsIndividuals with a history of confirmed EBV-IM had an 88% increased overall risk of malignancy (hazard ratio [HR]:1·88, 95% confidence interval [CI]: 1·42–2·49) and a five-fold risk of hematologic malignancies (HR 5·04, 95% CI: 3·07–8·25), compared to those without IM. Similar estimates were observed in the sibling analysis. The overall risk of malignancy was greater for EBV-IM with complications (HR 8·93, 95% CI: 3·35–23·81) than that for EBV-IM without complications (HR 1·35, 95% CI: 1·20–1·53). EBV-IM duration was related to increased risk of malignancy in a dose-response way. Notably, the significant elevated risk of overall malignancy was observed in the first two years after EBV-IM onset (rate ratio [RR] 4·44, 95% CI: 2·75–7·17) and attenuated thereafter.ConclusionEBV-IM was associated with an increased risk in malignancy, particularly hematologic malignancies and in the first two years following IM exposure. Our findings suggest an important time-window for early screening of the EBV-attributed malignancy

Caveolin-1 expression in different types of psoriatic lesions: Analysis of 66 cases

Background: Caveolin-1 is a key structural and functional protein. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. Objectives: To examine the expression of caveolin-1 in skin biopsies from normal subjects, patients, and subjects with the three respective isoforms of psoriasis (psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis). The expression level of caveolin-1 was compared among psoriasis vulgaris, localized pustular psoriasis, erythrodermic psoriasis, and normal subjects. Materials and Methods: Using immunohistochemical methods, caveolin-1 protein expression was assayed in four groups. An analysis was conducted on skin samples obtained from 22 normal subjects and 28 patients with psoriasis vulgaris, 22 patients with localized pustular psoriasis, and 16 patients with erythrodermic psoriasis. The statistical analysis of the scoring criteria reflecting the level of Caveolin-1 immunostaining between different groups was determined using the Mann-Whitney U-test. Results: In the normal skin, intense and consistent caveolin-1 staining was present in 22 cases. The Caveolin-1 protein was significantly reduced and showed very weak or absent staining within the tissues of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis (respective P 0.05). Conclusion: The finding of this study was consistent with a downregulation of Caveolin-1, which might serve as an etiological factor in the development of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis. Further mechanistic investigations are required to prove that Caveolin-1 protein has the potential and may be a novel target for therapy of psoriasis vulgaris, localized pustular psoriasis, and erythrodermic psoriasis

Screening for Biomarkers for Progression from Oral Leukoplakia to Oral Squamous Cell Carcinoma and Evaluation of Diagnostic Efficacy by Multiple Machine Learning Algorithms

The aim of the study is to identify key genes during the progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC) and predict effective diagnoses. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to identify seven genes associated with the progression from OL to OSCC. Twelve machine learning algorithms including k-nearest neighbor (KNN), neural network (NNet), and extreme gradient boosting (XGBoost) were used to construct multi-gene models, which revealed that each model had good diagnostic efficacy. The functional mechanism or the pathways associated with these genes were evaluated using enrichment analysis, subtype clustering, and immune infiltration analysis. The enrichment analysis revealed that the genes enriched were associated with the cell cycle, cell division, and intracellular energy metabolism. The immunoassay results revealed that the genes primarily affected the infiltration of proliferating T cells and macrophage polarization. Finally, a nomogram and Kaplan–Meier survival analysis were used to predict the prognostic efficacy of key genes in OSCC patients. The results showed that genes could predict the prognosis of the patients, and patients in the high-risk group had a poor prognosis. Our study identified that the seven key genes, including DHX9, BCL2L12, RAD51, MELK, CDC6, ANLN, and KIF4A, were associated with the progression from OL to OSCC. These genes had good diagnostic efficacy and could be used as potential biomarkers for the prognosis of OSCC patients

Spatiotemporal dynamics of free-living and particle-associated Vibrio communities in the northern Chinese marginal seas

Vibrio species are associated with human health and play important roles in the carbon cycle. The interest in the Vibrio ecology in marine pelagic environments has increased in recent years, and the correlations between the Vibrio community structure and various environmental factors have been demonstrated. However, the identification of planktonic Vibrio species and their relationship with particulate matter are unclear. Here, we elucidated the spatiotemporal dynamics of Vibrio diversity and in relation to environmental factors in the northern Chinese marginal seas, which feature complex and ever-changing environmental conditions. Vibrio abundance derived from quantitative PCR analysis was higher in summer (~1.4 × 106 copies liter-1) than in winter (~1.9 × 105 copies liter-1). Interestingly, the average amount of free-living (on a 0.22-μmpore- size filter membrane) Vibrio was higher (~3.89 times) than that of particleassociated Vibrio (on a 3-μm-pore-size filter membrane), making it likely that the preferential lifestyle of the planktonic Vibrio community was free living. Shifts in Vibrio community composition identified by high-throughput amplicon sequencing of the Vibrio-specific 16S rRNA gene were observed at both spatial and temporal scales, which were mainly driven by temperature, dissolved oxygen, ammonium, salinity, nitrite, and phosphate. The most prominent operational taxonomic units in summer were closely related to Vibrio campbellii and Vibrio caribbeanicus and shifted to those affiliated with Vibrio atlanticus in winter. Our study demonstrated abundant and diverse Vibrio populations in the northern Chinese marginal seas, contributing to a better understanding of their potential ecological roles in these ecosystems.</p

Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy.

Angiotensin converting enzyme 2 (ACE2) is a key receptor present on cell surfaces that directly interacts with the viral spike (S) protein of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is proposed that inhibiting this interaction can be promising in treating COVID-19. Here, the presence of ACE2 in extracellular vesicles (EVs) is reported and the EV-ACE2 levels are determined by protein palmitoylation. The Cys141 and Cys498 residues on ACE2 are S-palmitoylated by zinc finger DHHC-Type Palmitoyltransferase 3 (ZDHHC3) and de-palmitoylated by acyl protein thioesterase 1 (LYPLA1), which is critical for the membrane-targeting of ACE2 and their EV secretion. Importantly, by fusing the S-palmitoylation-dependent plasma membrane (PM) targeting sequence with ACE2, EVs enriched with ACE2 on their surface (referred to as PM-ACE2-EVs) are engineered. It is shown that PM-ACE2-EVs can bind to the SARS-CoV-2 S-RBD with high affinity and block its interaction with cell surface ACE2 in vitro. PM-ACE2-EVs show neutralization potency against pseudotyped and authentic SARS-CoV-2 in human ACE2 (hACE2) transgenic mice, efficiently block viral load of authentic SARS-CoV-2, and thus protect host against SARS-CoV-2-induced lung inflammation. The study provides an efficient engineering protocol for constructing a promising, novel biomaterial for application in prophylactic and therapeutic treatments against COVID-19

The NAD⁺ that is spontaneously released from M-MSNs@NAD⁺ can not increase the intracellular NAD⁺ and ATP levels in H₂O₂-treated PC12 cells.

<p>(A) The concentration of NAD⁺ that was spontaneously released from the 50 µg/mL M-MSNs@NAD⁺ into the media. NAD⁺ concentrations were measured by the recycling assay at various time points after the M-MSNs@NAD⁺ were added into the media. The peak NAD⁺ concentration was approximately 4 µM, which decreased gradually with time. N = 3. Data were collected from three independent experiments. *, <i>p</i><0.05. (B) Treatment of PC12 cells with 10 ∼ 100 µM NAD⁺ could not increase the intracellular NAD⁺ levels in H₂O₂-treated PC12 cells. N = 12. Data were collected from three independent experiments. (C) When the astrocytes were treated with 10 ∼ 100 µM NAD⁺, no increase in the intracellular NAD⁺ was observed. N = 7. Data were collected from two independent experiments. (D) Treatment of PC12 cells with 5 µM NAD⁺ could not increase the intracellular ATP levels in H₂O₂-treated PC12 cells. N = 15∼19. Data were collected from four independent experiments. (E) Treatment of astrocytes with 5 µM NAD⁺ could not increase the intracellular ATP levels. N = 7∼8. Data were collected from two independent experiments.</p