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The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis. [ABSTRACT FROM AUTHOR]

Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods. [ABSTRACT FROM AUTHOR]

This paper uses pollen climate analysis and coexistence analysis to systematically analyze the climatic evolution of the Shahejie Formation in the Chezhen Depression, Bohai Bay Basin, eastern China and discusses the relationship between palaeoclimatic evolution and lake level rise. The results show that the sedimentary period of the Shahejie Formation in the Chezhen Depression had an overall temperature change trend from hot to cold and simultaneously experienced a dry and wet balance-wet-dry and wet balance-wet transition process. The climatic parameters of the Shahejie Formation in the Chezhen Depression include a mean annual temperature of 8.1°C–15.1°C, a mean coldest monthly temperature of −0.1°C–2°C, a mean warmest monthly temperature of 18.6°C–28°C, a mean annual precipitation of 389–1164 mm, a wettest monthly precipitation amount of 215–262 mm, and a driest monthly precipitation amount of 8–48 mm. Climate change is believed to affect the rise and fall of lake levels to some extent. The quantitative reconstruction of these climatic parameters allows researchers to more intuitively understand the geological background of the Chezhen Depression and guide the exploration and development of oil and gas resources. [ABSTRACT FROM AUTHOR]

The sandstone of the third member of the Funing Formation (E1f3) in the northern slope zone of the Gaoyou Sag has the typical characteristics of high porosity and ultralow permeability, which makes it difficult for oil to flow. In this study, the lithological characteristics, sedimentary facies, diagenetic characteristics, pore structure, and seepage ability of this sandstone are characterized in detail. Correlation analysis is used to reveal the reason for the sandstone high porosity-low permeability phenomenon in the study area. The results indicate that this phenomenon is controlled mainly by the following three factors: 1) the sedimentary environment is the initial affecting factor, whereby the deposition of a large number of fine-grained materials reduces the primary pores of sandstone. 2) The Funing Formation has undergone strong compaction and cementation, which have led to the removal of most of the primary pores and a reduction in size of the throat channels. 3) Owing to fluid activity during the later stage of diagenesis, sandstone underwent intense dissolution and a large number of particles (feldspar and lithic debris) formed many dissolution pores (accounting for nearly 60% of the total pore space). Among these factors, dissolution has contributed the most to the development of high porosity-low permeability phenomenon. This is mainly attributed to the inhomogeneous dissolution process, whereby the degree of particle dissolution (e.g. feldspar) exceeds that of cementing minerals (clay and carbonate minerals). The secondary dissolution pores have increased the porosity of sandstone in the study area; however, the pore connectivity (permeability) has not been significantly improved, thus resulting in the special high porosity-low permeability characteristics of this sandstone. [ABSTRACT FROM AUTHOR]

Permeability is difficult to evaluate in reservoir petrophysics property, especially in low porosity–permeability reservoir. The conventional permeability estimation model with establishment of the regression relationship between permeability and porosity is not applicable. This regression hypothesis based on the correlation between porosity and permeability (logarithm) is not available in low porosity–permeability reservoir. It remains a challenging problem in tight and heterogeneous formations' petrophysical interpretation. Feature engineering process, as the most significant procedure in data-driven analytics, indicates that accurate modelling should be based on the main control factor on permeability ignoring its concrete mathematical expression. To select the factors that influence the main function of the model, and use the appropriate model to carry out the model structure, fusion and optimization is the main task to permeability estimation in low porosity–permeability reservoirs. Fuzzy logic, as a widely used approach in estimation of permeability, can be used to estimate the permeability with the advantage of tolerance. Its good adaptation in objective contradictory concepts and false elements in computational processes outweighs the traditional method on permeability estimation which always lies in a wide distribution of orders of magnitude. The research takes the permeability estimation issue in Mesozoic strata, Gaoqing area as example. The area of study mainly contains reservoirs with low-to-ultra-low porosity–permeability. The relationship between porosity and permeability is somewhat certain but insufficient using the regression method to predict. The research combined specialized feature engineering process with the fuzzy logic analysis to predict permeability. First, this paper analyzes that the main control factors of permeability in the region is the homogenization by diagenetic with statistical multivariate variance analysis SNK (Student–Newman–Keuls) method. It can be characterized by Δ φ , the changing degrees of porosity. To characterize the permeability response in well logs, the variables standing for a comprehensive reflection of the formation hydrology, lithology, and diagenesis are selected in the result of the electrofacies, SP, LLS, AC by multivariate variable selection method. The study is trying to combine the logging principle to explain its physical meaning by the statistical results. For discrete variables like electrofacies in modelling, scale quantization should be conducted by the optimal scale analysis considering discrete variables influences on permeability instead of manual labelling by numbers. Finally, the fuzzy logic analysis is carried out to achieve the results. The study makes a comparison of results in three ways to indicate the importance of feature engineering. That is, improved results with optimized model, model without feature engineering, and ordinary regression model. The optimized model with feature engineering predicts the permeability more conformed to the core data. [ABSTRACT FROM AUTHOR]

A novel modeling strategy is presented for simulating the blast furnace iron making process. Such physical and chemical phenomena are taking place across a wide range of length and time scales, and three models are developed to simulate different regions of the blast furnace, i.e., the tuyere model, the raceway model and the shaft model. This paper focuses on the integration of the three models to predict the entire blast furnace process. Mapping output and input between models and an iterative scheme are developed to establish communications between models. The effects of tuyere operation and burden distribution on blast furnace fuel efficiency are investigated numerically. The integration of different models provides a way to realistically simulate the blast furnace by improving the modeling resolution on local phenomena and minimizing the model assumptions. [ABSTRACT FROM AUTHOR]

Mycotoxins produced by different species of fungi may coexist in cereals and feedstuffs, and could be highly toxic for humans and animals. For quantification of multiple mycotoxins in cereals, we developed a paper-based mycotoxin immune-affinity array. First, paper-based microzone arrays were fabricated by photolithography. Then, monoclonal mycotoxin antibodies were added in a copolymerization reaction with a cross-linker to form an immune-affinity monolith on the paper-based microzone array. With use of a competitive immune-response format, paper-based mycotoxin immune-affinity arrays were successfully applied to detect mycotoxins in samples. The detection limits for deoxynivalenol, zearalenone, T-2 toxin, and HT-2 toxin were 62.7, 10.8, 0.36, and 0.23 μg·kg-1, respectively, which meet relevant requirements for these compounds in food. The recovery rates were 81-86% for deoxynivalenol, 89-117% for zearalenone, 79-86% for T-2 toxin, and 78-83% for HT-2 toxin, and showed the paper-based immune-affinity arrays had good reproducibility. In summary, the paper-based mycotoxin immune-affinity array provides a sensitive, rapid, accurate, stable, and convenient platform for detection of multiple mycotoxins in agro-foods.Paper-based immune-affinity monolithic array. DON deoxynivalenol, HT-2 HT-2 toxin, T-2 T-2 toxin, PEGDA polyethylene glycol diacrylate, ZEN zearalenone [ABSTRACT FROM AUTHOR]

Sulfamethoxazole (SMX) was decomposed by using gamma irradiation in the presence of different additives such as NO , NO , Cr(VI), 2-propanol, and tert-butanol. The results demonstrated that NO , NO , 2-propanol, and tert-butanol inhibited SMX radiolytic removal. However, there existed a synergetic effect for radiolytic removal of the mixture containing SMX and Cr(VI). At an absorbed dose of 150 Gy, the removal percentages of SMX and Cr(VI) in the mixture were 73.5 and 84.6%, respectively, which was higher than the removal percentages of 70.6 and 4.1% for the single component of SMX and Cr(VI). This provides us an insight into treating the combined pollution in micro-polluted water. The SMX radiolytic removal followed a pseudo first-order reaction kinetic model, and the rate constant ratios of ·OH, e , and H· towards SMX radiolysis were 10.4:1:2.9. In addition, 24-h bio-inhibitory to the macroalgae of SMX solution during gamma irradiation reached the maximum of 0.85 at an adsorbed dose of 100 Gy, then gradually decreased with the increasing adsorbed dose. Based on LC-MS analysis and quantum chemical calculation, the degradation intermediates were determined and concluded that SMX radiolytic removal was mainly via ·OH radical attack and direct decomposition of SMX molecule by gamma ray. [ABSTRACT FROM AUTHOR]

Background: Carbohydrate sulfotransferases 11-13 (CHST11-13), that catalyze the transfer of sulfate to position 4 of the GalNAc residue of chondroitin, have been implicated in various diseases.Aim: This study aimed to clarify the association of CHST11-13 expression with metastasis and drug sensitivity in hepatocellular carcinoma (HCC) cells.Methods: We measured the levels of CHST11 and CHST13 in a series of HCC cells using real-time PCR and Western blotting. After RNAi and forced expression treatment of CHST11 and CHST13 in MHCC97L and MHCC97H cells, metastatic potential and drug sensitivity of the two cells were investigated with ECM invasion assay, drug sensitivity assay, and in vivo antitumor activity assay. By real-time PCR and Western blotting, we explored the possible impacts of these two genes on mitogen-activated protein kinase (MAPK) signal pathway. MAPK pathway was blocked by PD98059 or SP600125 to elucidate the effects of MAPK pathway on metastasis and chemosensitivity.Results: Significantly reduced levels of CHST11 and CHST13 were observed in highly invasive MHCC97H cells compared with those of MHCC97L cell line with low metastatic potential. Decreased or forced expression of CHST11 and CHST13 altered metastatic potential and drug sensitivity of MHCC97L and MHCC97H cells. Remarkable alteration of MAPK activity was shown in two HCC cells with genetic manipulation. Conversely, pharmacologic inhibition of the MAPK pathway suppressed invasive potential and rescued drug sensitivity of MHCC97H cells.Conclusions: Our results have demonstrated that CHST11 and CHST13 negatively modulate metastasis and drug resistance of HCC cells probably via oncogenic MAPK signal pathway. [ABSTRACT FROM AUTHOR]

Gamma irradiation-induced decomposition of ciprofloxacin (CIP) was elucidated with different additives, such as CO, NO, NO, humic acid, methanol, 2-propanol, and tert-butanol. The results show that low initial concentration and acidic condition were favorable for CIP removal during γ irradiation. By contrast, radiolytic decomposition of CIP was inhibited with the addition of anions and organic additives. As a strong carcinogen, Cr was especially mixed with CIP to produce combined pollution. It is noteworthy that the removal of the mixture of CIP and Cr presented a synergistic effect; the degradation efficiency of the two pollutants was markedly improved compared to that of the single pollutant during γ irradiation. Based on the results of quantum chemical calculations and LC-MS analysis, we determined seven kinds of degradation intermediates and presented the CIP degradation pathways, which were mainly attributed to the oxidation process of hydroxyl radicals OH· and the direct decomposition of CIP molecules. [ABSTRACT FROM AUTHOR]

We are sorry for the inconvenience. These authors contributed equally: Yaoting Sun, Sathiyamoorthy Selvarajan, Zelin Zang, Wei Liu, Yi Zhu, Hao Zhang Correction to: I Cell Discovery i (2022) 8:85 https://doi.org/10.1038/s41421-022-00442-x published online 06 September 2022 In this article, the authors have found an error in Data Availability section, the iProX ID is incorrect. [Extracted from the article]

The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-β1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-β1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-β1 level, tumor differentiation, lymph node metastasis, and clinical stage ( p < 0.01). Our findings support the possibility that Axl is a significant regulator of invasion and chemosensitivity, and it means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor. [ABSTRACT FROM AUTHOR]

Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells. [ABSTRACT FROM AUTHOR]

The objective of this study is to clarify the possible role and mechanism of Axl in the tumorigenicity and metastasis process of hepatocellular carcinoma. The mRNA and protein expression levels of Axl in MHCC97-H and MHCC97-L cell lines were evaluated by real-time PCR and Western blot analysis. The key factor of phosphatidylinositol-3-kinase (PI3K)/Akt-p21-activated kinases-1 (PAK1) signaling pathway was studied after Axl expression was downregulated by shRNA. Finally, we analyzed the expression status of Axl protein expression in hepatocellular carcinoma tissues and its relationship with the prognosis of hepatocellular carcinoma. Axl was observed to be higher expressed in MHCC97-H cell lines compared to MHCC97-L cell lines. The downregulation of Axl in MHCC97-H cell lines resulted in the inhibition of the invasion ability of MHCC97-H cells both in vitro and in vivo. Interestingly, blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion. Finally, the Axl protein expression was positively correlated with differentiation, lymph node metastasis, and clinical stage in patients with hepatocellular carcinoma patients (all P < 0.01). These findings suggest that Axl can also regulate the metastasis process of hepatocellular carcinoma and may serve as a new prognostic marker and therapeutic target for treating hepatocellular carcinoma metastasis. [ABSTRACT FROM AUTHOR]

The effects of γ-irradiation pretreatment on anaerobic digestibility of sewage sludge was investigated in this paper. Parameters like solid components, soluble components, and biogas production of anaerobic digestion experiment for sewage sludge were measured. The values of these parameters were compared before and after γ-irradiation pretreatment. Total solid (TS), volatile solid (VS), suspended solid (SS), volatile suspended solid (VSS), and average floc size of samples decreased after γ-irradiation treatment. Besides, floc size distribution of sewage sludge shifted from 80–100 μm to 0–40 μm after γ-irradiation treatment at the doses from 0 to 30 kGy, which indicated the disintegration of sewage sludge. Moreover, microbe cells of sewage sludge were ruptured by γ-irradiation treatment, which resulted in the release of cytoplasm and increase of soluble chemical oxygen demand (SCOD). Both sludge disintegration and microbe cells rupture enhanced the subsequent anaerobic digestion process, which was demonstrated by the increase of accumulated biogas production. Compared with digesters fed with none irradiated sludge, the accumulated biogas production increased 44, 98, and 178 mL for digesters fed sludge irradiated at 2.48, 6.51, and 11.24 kGy, respectively. The results indicated that γ-irradiation pretreatment could effectively enhance anaerobic digestibility of sewage sludge, and correspondingly, could accelerate hydrolysis process, shorten sludge retention time of sludge anaerobic digestion process. [ABSTRACT FROM AUTHOR]

Purpose: The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy. Methods: In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system. Results: The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation. Conclusion: The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers. [ABSTRACT FROM AUTHOR]