Cancer cells sustain high levels of glycolysis and glutaminolysis via reprogramming of intracellular metabolism, which represents a driver of hepatocellular carcinoma (HCC) progression. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. Herein, we collected HCC tissues and noncancerous liver tissues and found hepatitis B virus X‐interacting protein (HBXIP) was found to be upregulated in HCC tissues and associated with poor prognosis. The N6‐methyladenosine (m6A) level of hypoxia‐inducible factor‐1α (HIF‐1α) in HCC cells was evaluated after the intervention of METTL3. The possible m6A site of HIF‐1α was queried and the binding relationship between METTL3 and HIF‐1α was verified. The interference of HBXIP suppressed HCC malignant behaviors and inhibited the Warburg effect in HCC cells. METTL3 was upregulated in HCC tissues and positively regulated by HBXIP. Overexpression of METTL3 restored cell metabolic reprogramming in HCC cells with partial loss of HBXIP. HBXIP mediated METTL3 to promote the metabolic reprogramming and malignant biological behaviors of HCC cells. The levels of total m6A in HCC cells and m6A in HIF‐1α were increased. METTL3 had a binding relationship with HIF‐1α and mediated the m6A modification of HIF‐1α. In conclusion, HBXIP drives metabolic reprogramming in HCC cells via METTL3‐mediated m6A modification of HIF‐1α.
On May 12, 2008, a strong earthquake with a magnitude of 8.0 (Ms) struck Wenchuan town, in the eastern Sichuan area of west China. Following the earthquake on May 18, the Southwest Jiaotong University organized a damage survey team and dispatched it to the affected area for the investigation into the damage and collection of information and data. This paper outlines the findings of this investigation on the earthquake disaster to mountain tunnels and geotechnical engineering. The systematic investigation, involving geological conditions, design documents, construction and maintenance records of the tunnels, has been conducted and the degree of damage to investigated tunnels has been assessed according to the width and length of cracks, the stability of the slope above the tunnel, and the condition of the groundwater inrush. The results show that the major damage of the mountain tunnels was mainly concentrated in the tunnel portals due to widespread landslides and rockfalls, and the inner part of investigated tunnels suffered moderate damages mainly due to fault displacements. It is hoped that the information shared herein could enhance the outstanding of seismic behavior of mountain tunnels and improve seismic design and construction procedures. damage investigation, wenchuan earthquake, mountain tunnels, ground failures
This study aimed to identify the differences in the oral microbial communities in saliva from patients with and without caries by performing sequencing with the Illumina MiSeq platform, as well as to further assess their relationships with environmental factors (salivary pH and iron concentration). Forty-three volunteers were selected, including 21 subjects with and 22 without caries, from one village in Gansu, China. Based on 966,255 trimmed sequences and clustering at the 97% similarity level, 1,303 species-level operational taxonomic units were generated. The sequencing data for the two groups revealed that (i) particular distribution patterns (synergistic effects or competition) existed in the subjects with and without caries at both the genus and species levels and (ii) both the salivary pH and iron concentration had significant influences on the microbial community structure.IMPORTANCE The significant influences of the oral environment observed in this study increase the current understanding of the salivary microbiome in caries. These results will be useful for expanding research directions and for improving disease diagnosis, prognosis, and therapy.
Abstract-In order to guarantee safe and reliable operation of electric vehicle batteries and to optimise their energy and capacity utilisation, it is indispensable to estimate their state-of-charge (SoC). This study aimed to develop a novel estimation approach based on the Grey model and Genetic Algorithms without the need of a high-fidelity battery model demanding high computation power. A SoC analytical model was established using the Grey System theory based on a limited amount of incomplete data in contrast to conventional methods. The model was further improved by applying a sliding window mechanism to adjust the model parameters according to the evolving operating status and conditions. In addition, the Genetic Algorithms were introduced to identify the optimal adjustment coefficient, λ, in a traditional Grey model (1, 1) model to further improve the source estimation accuracy. For experimental verification, two types of Lithium-ion batteries were used as the device-under-test that underwent typical passenger car driving cycles. The proposed SoC estimation method were verified under diverse battery discharging conditions and it demonstrated superior accuracy and repeatability compared to the benchmarking GM method.
INHBA-encoded inhibin β A is a member of the transforming growth factor-β (TGF-β) superfamily. INHBA has been reported to be implicated in the progression of multiple types of cancer including ovarian cancer (OC). However, the mechanisms by which INHBA affects OC progression are not well-characterized. The aim of our study was to explore the prognostic value of INHBA for different stages and grades of OC and to identify the possible mechanisms by which INHBA promotes OC progression. Our results demonstrated that INHBA was specifically expressed in OC epithelium, and higher expression was associated with higher risk of mortality in patients with advanced and higher-grade serous OC (SOC). In addition, knockdown of INHBA in cancer cells impaired cancer xenograft growth through reducing OC stromal fibroblast activation in vivo. Further results confirmed that Smad2 signaling pathway was involved in INHBA-induced stromal fibroblast activation, and inhibiting this pathway could effectively reverse activation of stromal fibroblasts. In summary, our results showed that blocking INHBA in cancer cells may be a potential therapeutic strategy to inhibit SOC progression.
As an emerging minimally invasive treatment method, percutaneous ablation is more and more widely used in the treatment of liver tumors. It has been recommended by guidelines for diagnosis and treatment of hepatocellular carcinoma (HCC) as a curative treatment alongside surgical resection and liver transplantation. In recent years, with the continuous advancement and innovation of percutaneous ablation technologies, their clinical efficacy and safety have been significantly improved, which has led to the expanded application of percutaneous ablation in the treatment of HCC—more and more patients who were previously considered unsuitable for ablation therapies are now being treated with percutaneous ablation. Obviously, percutaneous ablation can reduce the risk of treatment changes from curative strategies to palliative strategies. Based on clinical practice experience, this review enumerates the advantages and disadvantages of different ablative modalities and summarizes the existing combinations of ablation techniques, thus will help clinicians choose the most appropriate ablative modality for each patient and will provide scientific guidance for improving prognosis and making evidence-based treatment decisions. In addition, we point out the challenges and future prospects of the ablation therapies, thereby providing direction for future research.
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