Deficiency in SLC25A15, a hypoxia-responsive gene, promotes hepatocellular carcinoma by reprogramming glutamine metabolism.

BACKGROUND & AIMS: The role of solute carrier family 25 member 15 (SLC25A15), a critical component of the urea cycle, in hepatocellular carcinoma (HCC) progression remains poorly understood. This study investigated the impact of SLC25A15 on HCC progression and its mechanisms. METHODS: We systematically investigated the function of SLC25A15 in HCC progression using large-scale data mining and cell, animal, and organoid models. Furthermore, we analyzed its involvement in reprogramming glutamine metabolism. RESULTS: SLC25A15 expression was significantly decreased in HCC tissues, and patients with low SLC25A15 levels had a poorer prognosis. Hypoxia-exposed HCC cells or tissues had lower SLC25A15 expression. A positive correlation between HNF4A, a transcription factor suppressed by hypoxia, and SLC25A15 was observed in both HCC tissues and cells. Modulating HNF4A levels altered SLC25A15 mRNA levels. SLC25A15 upregulated SLC1A5, increasing glutamine uptake. The reactive metabolic pathway of glutamine was increased in SLC25A15-deficient HCC cells, providing energy for HCC progression through additional lipid synthesis. Ammonia accumulation due to low SLC25A15 levels suppressed the expression of OGDHL (oxoglutarate dehydrogenase L), a switch gene that mediates SLC25A15 deficiency-induced reprogramming of glutamine metabolism. SLC25A15-deficient HCC cells were more susceptible to glutamine deprivation and glutaminase inhibitors. Intervening in glutamine metabolism increased SLC25A15-deficient HCC cells' response to anti-PD-L1 treatment. CONCLUSION: SLC25A15 is hypoxia-responsive in HCC, and low SLC25A15 levels result in glutamine reprogramming through SLC1A5 and OGDHL regulation, promoting HCC progression and regulating cell sensitivity to anti-PD-L1. Interrupting the glutamine-derived energy supply is a potential therapeutic strategy for treating SLC25A15-deficient HCC. IMPACT AND IMPLICATIONS: We first demonstrated the tumor suppressor role of solute carrier family 25 member 15 (SLC25A15) in hepatocellular carcinoma (HCC) and showed that its deficiency leads to reprogramming of glutamine metabolism to promote HCC development. SLC25A15 can serve as a potential biomarker to guide the development of precision therapeutic strategies aimed at targeting glutamine deprivation. Furthermore, we highlight that the use of an inhibitor of glutamine utilization can enhance the sensitivity of low SLC25A15 HCC to anti-PD-L1 therapy.

HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation.

BACKGROUND: Sepsis-associated encephalopathy (SAE) always manifests with severe inflammatory symptoms and cognitive impairment. High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine. In this study we investigated the role of HMGB1 in SAE. METHODS: An SAE mouse model was established through cecal ligation and puncture surgery and then injected with adenovirus short hairpin RNA (Ad-sh)-HMGB1 or Ad-sh-myeloid differentiation protein (MD-2). The cognitive impairment and pathological injury in mice of different groups were evaluated using the Morris water maze experiment, Y-maze test, tail suspension test, fear conditioning test, and haematoxylin-eosin staining. The expressions of HMGB1 (fully reduced and disulfide (ds)HMGB1), MD-2, and NLRP3 in SAE mice were determined. Then, levels of inflammatory cytokines were measured. The binding relation between HMGB1 and MD-2 was predicted and certified. Additionally, MD-2 was downregulated to verify the role of the binding of HMGB1 and MD-2 in neuroinflammation and cognitive impairment in SAE. RESULTS: Expressions of HMGB1, MD-2, NLRP3, and inflammatory cytokines were enhanced in the SAE mouse model, which were in parallel with impaired cognitive function. HMGB1 silencing resulted in downregulated NLRP3 expression and alleviated neuroinflammation and cognitive impairment in SAE mice. Mechanically, dsHMGB1 bound to MD-2 to activate NLRP3, thereby exacerbating neuroinflammation and cognitive impairment in SAE mice. The limited binding of HMGB1 and MD-2 downregulated NLRP3 expression to alleviate neuroinflammation and cognitive impairment in SAE mice. CONCLUSION: HMGB1 was overexpressed in SAE, and dsHMGB1 bound to MD-2 to activate NLRP3 inflammasome, inducing neuroinflammation and cognitive impairment in SAE.

Artemether Attenuates Aß25-35-Induced Cognitive Impairments by Downregulating Aß, BACE1, mTOR and Tau Proteins.

BACKGROUND: Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (Aß) induced neural apoptosis. Moreover, overexpression of ß-secretase 1 (BACE1), Aß, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symptoms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, possesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily penetrate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment. METHODS: The effect of artemether on memory protection and the associated molecular mechanisms were investigated in an Aß25-35 induced cognitive impairments rat model. RESULTS: Results of the in vivo study showed that oral administration of artemether significantly attenuated Aß25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aß, BACE1, mTOR, and Tau proteins in N2a cells. CONCLUSIONS: The beneficial effect of artemether against Aß 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aß, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.

Estimation of the relative contributions of forest areal expansion and growth to China's forest stand biomass carbon sequestration from 1977 to 2018.

As a prominent part of global and regional terrestrial carbon (C) pools, increases in forest biomass C sinks can be attributed to either forest areal expansion (FAE) or increased biomass C density (IBCD). Accurate estimates of the relative contributions of FAE and IBCD to forest C sequestration can improve our understanding of forest C cycling processes and will help to formulate rational afforestation policies to cope with global warming. In this study, the Continuous Biomass Expansion Factor (CBEF) model and Forest Identity concept were used to map the spatiotemporal variation of the relative contribution of FAE and IBCD to the C sequestration of forest (natural and planted forests) in China and seven regions during the past 40 years. Our results suggest that: (1) total forest biomass C density and stocks of forest increased from 35.41 Mg C ha-1 and 4128.50 Tg C to 43.95 Mg C ha-1 and 7906.23 Tg C in China from 1977 to 2018, respectively; (2) for all forests, the IBCD has been a smaller contributor to C sinks than FAE in China from 1977 to 2018 (33.27 vs. 66.73%); (3) the contribution of FAE to C sinks is greater than that of IBCD in planted forests (63.99 vs. 36.01%), while in natural forests, IBCD has a larger contribution than FAE (57.82 vs. 42.18%) from 1977 to 2018 and the relative contribution of FAE has exceeded IBCD in the last decade; and (4) these patterns varied at the regional level such that the relative contribution of FAE increased for planted forests in most regions but for natural forests, IBCD gradually reached saturation and C stocks declined in northern regions in the last decade. The results from this study suggest that total biomass C sinks will keep increasing because of the increased forest area contributed by afforestation and the relatively young trees in planted forests. This study facilitates a more comprehensive assessment of forest C budgets and improves our understanding of ecological mechanisms of forest biomass carbon stock and dynamics.

STAT1-induced upregulation of LINC00467 promotes the proliferation migration of lung adenocarcinoma cells by epigenetically silencing DKK1 to activate Wnt/ß-catenin signaling pathway.

Long non-coding RNAs (lncRNAs) have been reported as essential regulators in human cancers, including lung adenocarcinoma (LUAD). In the present study, we found that lncRNA long intergenic non-protein coding RNA 467 (LINC00467) was expressed higher in TCGA LUAD samples and predicted poor prognosis in LUAD patients. High expression of LINC00467 was further detected in LUAD cell lines. Functionally, high expression level of LINC00467 promoted LUAD cell proliferation and migration, indicating that LINC00467 exerted oncogenic functions in LUAD progression. Considering the upregulation of LINC00467 in LUAD, we further detected the activator of LINC00467 promoter. Combining with bioinformatics analysis and mechanism experiments, we determined that LINC00467 was activated by STAT1 in LUAD. Moreover, high expression of LINC00467 was found to be associated with the activation of Wnt/ß-catenin signaling pathway. Rescue assays demonstrated that dickkopf WNT signaling pathway inhibitor 1 (DKK1; an inhibitor of Wnt/ß-catenin signaling pathway) and Wnt/ß-catenin signaling involved in DKK1-mediated LUAD cell proliferation and migration. Furthermore, LINC00467 was located in the nucleus of LUAD cell lines and negatively regulated DKK1 in LUAD cells. Mechanistically, we determined that LINC00467 epigenetically silenced DKK1 by recruiting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) to DKK1 promoter. Collectively, we determined that STAT1-induced upregulation of LINC00467 promoted LUAD progression by epigenetically silencing DKK1 to activate Wnt/ß-catenin signaling pathway.

Improving near-eye display resolution by polarization multiplexing.

We present here an optical approach to boost the apparent pixel density by utilizing the superimposition of two shifted-pixel grids generated by a Pancharatnam-Berry deflector (PBD). The content of the two shifted pixel grids are presented to the observer's eye simultaneously using a polarization-multiplexing method. Considering the compact and lightweight nature of PBD, this approach has potential applications in near-eye display systems. Moreover, the same concept can be extended to projection displays with proper modifications.

Foveated imaging for near-eye displays.

The angular resolution of current near-eye display devices is still far below human-eye acuity. How to achieve retina-level resolution while keeping wide field-of-view (FOV) remains a great challenge. In this work, we demonstrate a multi-resolution foveated display with two display panels and an optical combiner. The first display panel provides a wide FOV but relatively low resolution for the surrounding region, while the second one offers an ultra-high resolution for the central fovea region, by an optical minifying system which enhances the effective resolution by 5 ×. In addition, a switchable Pancharatnam-Berry phase deflector is employed to shift the high-resolution region. The proposed design effectively reduces the pixelation and screen-door effect in near-eye displays.

Risk Models for Predicting the Recurrence and Survival in Patients With Hepatocellular Carcinoma Undergoing Radio-Frequency Ablation.

Background: Hepatocellular carcinoma (HCC) patients have a poor prognosis after radio-frequency ablation (RFA), and investigating the risk factors affecting RFA and establishing predictive models are important for improving the prognosis of HCC patients. Methods: Patients with HCC undergoing RFA in Shenzhen People's Hospital between January 2011 and December 2021 were included in this study. Using the screened independent influences on recurrence and survival, predictive models were constructed and validated, and the predictive models were then used to classify patients into different risk categories and assess the prognosis of different categories. Results: Cox regression model indicated that cirrhosis (hazard ratio [HR] = 1.65), alpha-fetoprotein (AFP) ⩾400 ng/mL (HR = 2.03), tumor number (multiple) (HR = 2.11), tumor diameter ⩾20 mm (HR = 2.30), and platelets (PLT) ⩾ 244 (109/L) (HR = 2.37) were independent influences for recurrence of patients after RFA. On the contrary, AFP ⩾400 ng/mL (HR = 2.48), tumor number (multiple) (HR = 2.52), tumor diameter ⩾20 mm (HR = 2.25), PLT ⩾244 (109/L) (HR = 2.36), and hemoglobin (HGB) ⩾120 (g/L) (HR = 0.34) were regarded as independent influences for survival. The concordance index (C-index) of the nomograms for predicting disease-free survival (DFS) and overall survival (OS) was 0.727 (95% confidence interval [CI] = 0.770-0.684) and 0.770 (95% CI = 0.821-7.190), respectively. The prognostic performance of the nomograms was significantly better than other staging systems by analysis of the time-dependent C-index and decision curves. Each patient was scored using nomograms and influencing factors, and patients were categorized into low-, intermediate-, and high-risk groups based on their scores. In the Kaplan-Meier survival curve, DFS and OS were significantly better in the low-risk group than in the intermediate- and high-risk groups. Conclusions: The 2 prediction models created in this work can effectively predict the recurrence and survival rates of HCC patients following RFA.

Revealing the Limitation Induced by Hydroxyl in Regulating Solvation Structure of Zn2+ and Overcoming Challenges with Hybrid Additives towards Highly Stable Zinc Anodes.

In the field of electrolyte design for aqueous zinc-ion batteries (AZIBs), additives containing hydroxyl have been demonstrated to effectively modulate the solvation structure of Zn2+. However, reported studies typically focus solely on the effectiveness of hydroxyl while neglecting the issues that emerge during solvation structure regulation. The strong electron-attracting capability of Zn2+ attracts electrons from the oxygen in hydroxyl, thereby weakening the strength of hydroxyl, the hydrogen evolution reaction (HER) is also pronounced. This work innovatively reveals the limitation of hydroxyl-containing additives and proposes a synergistic regulation strategy based on hybrid additives. Arginine with a high isoelectric point is introduced into the electrolyte system containing hydroxyl additives. The protonation effect and electrostatic attraction of arginine enable it to absorb protons at the anode released by the weakened hydroxyl, thereby compensating for the limitation of hydroxyl additives. Under the synergistic action of hybrid additives, the Zn|Zn battery achieved stable deposition/stripping for over 1200 hours under 10 mA cm-2 and 10 mAh cm-2. Moreover, the Zn|Cu battery cycled for over 570 hours with a high Coulombic efficiency of 99.82%. This study presents a pioneering perspective for the further application of AZIBs.

Exploring the factors affecting the occurrence of postoperative MVI and the prognosis of hepatocellular carcinoma patients treated with hepatectomy: A multicenter retrospective study.

OBJECTIVE: To investigate the influencing factors affecting the occurrence of microvascular invasion (MVI) and the prognosis of hepatocellular carcinoma (HCC) patients treated with hepatectomy, and to explore how MVI affects prognosis in subgroups with different prognostic factors. METHODS: Clinical data of a total of 1633 patients treated surgically for HCC in four treatment centers were included, including 754 patients with MVI. By using the Cox risk regression model and the Mann-Whitney U-test, the common independent influences on prognosis and MVI were made clear. The incidence of MVI in various subgroups was then examined, as well as the relationship between MVI in various subgroups and prognosis. RESULTS: The Cox risk regression model showed that MVI, Child-Pugh classification, alpha-fetoprotein (AFP), hepatocirrhosis, tumor diameter, lymphocyte-to-monocyte ratio (LMR), and, Barcelona clinic liver cancer (BCLC) grade were independent determinants of overall survival (OS), and MVI, AFP, hepatocirrhosis, tumor diameter, and LMR were influencing determinants for disease-free survival (DFS). The receiver operating characteristic (ROC) curve showed that MVI was most closely associated with patient prognosis compared to other prognostic factors. AFP, hepatocirrhosis, tumor diameter, and LMR were discovered to be common influences on the prognosis of patients with HCC and MVI when combined with the results of the intergroup comparison of MVI. After grouping, it was showed that patients with hepatocirrhosis, positive AFP (AFP ≥ 20 ng/mL), tumor diameter >50 mm, and LMR ≤3.4 had a significantly higher incidence of MVI than patients in other subgroups, and all four subgroups of MVI-positive patients had higher rates of early recurrence and mortality (p < 0.05). CONCLUSIONS: MVI was found to be substantially linked with four subgroups of HCC patients with hepatocirrhosis, positive AFP, tumor diameter >50 mm, and LMR ≤3.4, and the prognosis of MVI-positive patients in all four subgroups tended to be worse.

A 10-m annual grazing intensity dataset in 2015-2021 for the largest temperate meadow steppe in China.

Mapping grazing intensity (GI) using satellites is crucial for developing adaptive utilization strategies according to grassland conditions. Here we developed a monitoring framework based on a paired sampling strategy and the classification probability of random forest algorithm to produce annual grazing probability (GP) and GI maps at 10-m spatial resolution from 2015 to 2021 for the largest temperate meadow in China (Hulun Buir grasslands), by harmonized Landsat 7/8 and Sentinel-2 images. The GP maps used values of 0-1 to present detailed grazing gradient information. To match widely used grazing gradients, annual GI maps with ungrazed, moderately grazed, and heavily grazed levels were generated from the GP dataset with a decision tree. The GI maps for 2015-2021 had an overall accuracy of more than 0.97 having significant correlations with the statistical data at city (r = 0.51) and county (r = 0.75) scales. They also effectively captured the GI gradients at site scale (r = 0.94). Our study proposed a monitoring approach and presented annual 10-m grazing information maps for sustainable grassland management.

Validation and refinement of cropland map in southwestern China by harnessing ten contemporary datasets.

Accurate cropland map serves as the cornerstone of effective agricultural monitoring. Despite the continuous enrichment of remotely sensed cropland maps, pervasive inconsistencies have impeded their further application. This issue is particularly evident in areas with limited valid observations, such as southwestern China, which is characterized by its complex topography and fragmented parcels. In this study, we constructed multi-sourced samples independent of the data producers, taking advantage of open-source validation datasets and sampling to rectify the accuracy of ten contemporary cropland maps in southwestern China, decoded their inconsistencies, and generated a refined cropland map (CroplandSyn) by leveraging ten state-of-the-art remotely sensed cropland maps released from 2021 onwards using the self-adaptive threshold method. Validations, conducted at both prefecture and county scales, underscored the superiority of the refined cropland map, aligning more closely with national land survey data. The refined cropland map and samples are publicly available to users. Our study offers valuable insights for improving agricultural practices and land management in under-monitored areas by providing high-quality cropland maps and validation datasets.

Unsupervised feature selection based on incremental forward iterative Laplacian score.

Feature selection facilitates intelligent information processing, and the unsupervised learning of feature selection has become important. In terms of unsupervised feature selection, the Laplacian score (LS) provides a powerful measurement and optimization method, and good performance has been achieved using the recent forward iterative Laplacian score (FILS) algorithm. However, there is still room for advancement. The aim of this paper is to improve the FILS algorithm, and thus, feature significance (SIG) is mainly introduced to develop a high-quality selection method, i.e., the incremental forward iterative Laplacian score (IFILS) algorithm. Based on the modified LS, the metric difference in the incremental feature process motivates SIG. Therefore, SIG offers a dynamic characterization by considering initial and terminal states, and it promotes the current FILS measurement on only the terminal state. Then, both the modified LS and integrated SIG acquire granulation nonmonotonicity and uncertainty, especially on incremental feature chains, and the corresponding verification is achieved by completing examples and experiments. Furthermore, a SIG-based incremental criterion of minimum selection is designed to choose optimization features, and thus, the IFILS algorithm is naturally formulated to implement unsupervised feature selection. Finally, an in-depth comparison of the IFILS algorithm with the FILS algorithm is achieved using data experiments on multiple datasets, including a nominal dataset of COVID-19 surveillance. As validated by the experimental results, the IFILS algorithm outperforms the FILS algorithm and achieves better classification performance.

Microbial Community Characterization and Molecular Resistance Monitoring in Geriatric Intensive Care Units in China Using mNGS.

Background: Surface pathogens in the ICU pose a global public health threat, especially to elderly patients who are immunocompromised. To detect these pathogens, unbiased methods such as metagenomic next-generation sequencing (mNGS) are increasingly utilized for environmental microbiological surveillance. Methods: In a six-month study from January to July 2022, we investigated microbial communities in Chinese geriatric ICUs by regularly monitoring multiple surfaces at three-month intervals. Using mNGS sequencing, we analyzed microorganisms present at eight specific locations within the ICU. Additionally, we compared pathogen profiles and drug resistance genes between patient cultures and environmental samples collected during the same period. Results: The microbial composition remained relatively stable over time, but significant differences in alpha diversities were observed among various surfaces such as floors, hands, pumps, trolleys, and ventilator inlets/outlets. Surfaces with high contact frequency for healthcare workers, including workstations, ventilator panels, trolleys, pumps, and beds, harbored pathogenic microorganisms such as Acinetobacter baumannii, Cutibacterium acnes, Staphylococcus haemolyticus, Pseudomonas aeruginosa, and Enterococcus faecium. Acinetobacter baumannii, particularly the carbapenem-resistant strain (CRAB), was the most frequently identified pathogen in geriatric ICU patients regardless of testing method used. The mNGS approach enabled detection of viruses, fungi, and parasites that are challenging to culture. Additionally, an abundance of drug resistance genes was found in almost all environmental samples. Conclusion: The microbial composition and abundance in the ICU remained relatively constant over time. The floor exhibited the highest microbial diversity and abundance in the ICU environment. Drug-resistant genes in the ICU environment may migrate between patients. Overall, mNGS is an emerging and powerful tool for microbiological monitoring of the hospital environment.

Hypoxia-responsive PPARGC1A/BAMBI/ACSL5 axis promotes progression and resistance to lenvatinib in hepatocellular carcinoma.

Emerging evidence has indicated that peroxisome proliferator-activated receptor-gamma coactivator-1α (PPARGC1A) is involved in hepatocellular carcinoma (HCC). However, its detailed function and up- and downstream mechanisms are incompletely understood. In this study, we confirmed that PPAGC1A is lowly expressed in HCC and is associated with poor prognosis using large-scale public datasets and in-house cohorts. PPAGC1A was found to impair the progression and sensitivity of HCC to lenvatinib. Mechanistically, PPAGC1A repressed bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) by inhibiting WNT/ß-catenin signaling. BAMBI mediated the function of PPARGC1A and regulated ACSL5 through TGF-ß/SMAD signaling. PPARGC1A/BAMBI regulated ROS production and ferroptosis-related cell death by controlling ACSL5. PPARGC1A/BAMBI/ACSL5 axis was hypoxia-responsive. METTL3 and WTAP silenced PPARGC1A in an m6A-YTHDF2-dependent way under normoxia and hypoxia, respectively. Metformin restored PPARGC1A expression by reducing its m6A modification via inhibiting METTL3. In animal models and patient-derived organoids, consistent functional data of PPARGC1A/BAMBI/ACSL5 were observed. Conclusions: These findings provide new insights into the role of the aberrant PPARGC1A/BAMBI/ACSL5 axis in HCC. And the mechanism of PPARGC1A dysregulation was explained by m6A modification. Metformin may benefit HCC patients with PPARGC1A dysregulation.

Suppression of mir-150-5p attenuates the anti-inflammatory effect of glucocorticoids in mice with ulcerative colitis.

Glucocorticoids have been widely used in the treatment of ulcerative colitis, but not all patients benefit from this therapy due to hormone resistance. Mir-150-5p has been reported to enhance the efficacy of glucocorticoids, and low serum mir-150-5p expression has been linked to glucocorticoid resistance in ulcerative colitis patients. The aim of this study was to elucidate the mechanisms of mir-150-5p regulation on glucocorticoid resistance. An ulcerative colitis mouse model was used to evaluate changes in ulcerative colitis symptoms, inflammatory factors, and glucocorticoid resistance-related gene expression. The results showed that mir-150-5p suppression with antagomirs did not significantly interfere with or enhance the induction of ulcerative colitis symptoms by dextran sulfate sodium, but it did attenuate the inflammation inhibitory effect of dexamethasone by abnormally regulating the expression of IL-17a, IL-10, IL-2 and IL-6 levels and myeloperoxidase activity. Mir-150-5p inhibition also induced a glucocorticoid-resistant gene expression profile in colon tissues of ulcerative colitis mice, with upregulation of p-ERK, p-JNK, and HSP90 and downregulation of p-GRa, FKBP4, and HDAC2 expression. Our results indicate that mir-150-5p suppression attenuates the anti-inflammatory effect of glucocorticoids and may function as a driver element in ulcerative colitis glucocorticoid resistance. AVAILABILITY OF DATA AND MATERIALS: All data and figures analyzed in this study are available from the corresponding author by request.

IHGA: An interactive web server for large-scale and comprehensive discovery of genes of interest in hepatocellular carcinoma.

Mining gene expression data is valuable for discovering novel biomarkers and therapeutic targets in hepatocellular carcinoma (HCC). Although emerging data mining tools are available for pan-cancer-related gene data analysis, few tools are dedicated to HCC. Moreover, tools specifically designed for HCC have restrictions such as small data scale and limited functionality. Therefore, we developed IHGA, a new interactive web server for discovering genes of interest in HCC on a large-scale and comprehensive basis. Integrative HCC Gene Analysis (IHGA) contains over 100 independent HCC patient-derived datasets (with over 10,000 tissue samples) and more than 90 cell models. IHGA allows users to conduct a series of large-scale and comprehensive analyses and data visualizations based on gene mRNA levels, including expression comparison, correlation analysis, clinical characteristics analysis, survival analysis, immune system interaction analysis, and drug sensitivity analysis. This method notably enhanced the richness of clinical data in IHGA. Additionally, IHGA integrates artificial intelligence (AI)-assisted gene screening based on natural language models. IHGA is free, user-friendly, and can effectively reduce time spent during data collection, organization, and analysis. In conclusion, IHGA is competitive in terms of data scale, data diversity, and functionality. It effectively alleviates the obstacles caused by HCC heterogeneity to data mining work and helps advance research on the molecular mechanisms of HCC.

Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression.

Long noncoding RNAs (lncRNA) regulate a number of aspects of cancer biology. Recent research has shown that lncRNAs can encode micropeptides that mediate their functions in tumors. Here, we revealed that the liver-specific putative lncRNA, AC115619, is expressed at low levels in hepatocellular carcinoma (HCC) and encodes a micropeptide, designated as AC115619-22aa. AC115619 played a crucial role in the regulation of tumor progression and was a prognostic indicator in HCC. The encoded micropeptide AC115619-22aa inhibited the progression of HCC by binding to WTAP and impeding the assembly of the N6-methyladenosine (m6A) methyltransferase complex, which regulates the expression of tumor-associated genes, such as SOCS2 and ATG14. AC115619 was cotranscribed with the adjacent upstream coding gene APOB, and hypoxia induced transcriptional repression of both APOB and AC115619 by controlling HIF1A/HDAC3 and HNF4A signaling. In animal and patient-derived models, AC115619-22aa reduced global m6A levels and suppressed tumor growth. In conclusion, this study establishes AC115619 and its encoded micropeptide as potential prognostic markers and therapeutic targets for patients with HCC. SIGNIFICANCE: A micropeptide encoded by lncRNA AC115619 impedes formation of the m6A methylation complex to lower m6A levels and reduce the growth of hepatocellular carcinoma.

Automatic Segmentation of Magnetic Resonance Images of Severe Patients with Advanced Liver Cancer and the Molecular Mechanism of Emodin-Induced Apoptosis of HepG2 Cells under the Deep Learning.

To improve the accuracy of clinical diagnosis of severe patients with advanced liver cancer and enhance the effect of chemotherapy treatment, the U-Net model was optimized by introducing the batch normalization (BN) layer and the dropout layer, and the segmentation training and verification of the optimized model were realized by the magnetic resonance (MR) image data. Subsequently, HepG2 cells were taken as the research objects and treated with 0, 10, 20, 40, 60, 80, and 100 µmol/L emodin (EMO), respectively. The methyl thiazolyl tetrazolium (MTT) method was used to explore the changes in cell viability, the acridine orange (AO)/ethidium bromide (EB) and 4',6-diamidino-2-phenylindole (DAPI) were used for staining, the Annexin V fluorescein isothiocyanate (FITC)/propidium iodide (PI) (Annexin V-FITC/PI) was adopted to detect the apoptosis after EMO treatment, and the Western blot (WB) method was used with the purpose of exploring the changes in protein expression levels of PARP, Bcl-2, and p53 in the cells after treatment. It was found that compared with the original U-Net model, the introduction of the BN layer and the dropout layer can improve the robustness of the U-Net model, and the optimized U-Net model had the highest dice similarity coefficient (DSC) (98.45%) and mean average precision (MAP) (0.88) for the liver tumor segmentation.

Effects and mechanism of microRNA­218 against lung cancer.

Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)­218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR­218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR­218 in XWLC­05 cells were markedly lower compared with those in immortalized lung epithelial BEAS­2B cells. The present study also demonstrated that overexpression of miR­218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC­05 and NSCLC cell line NCI­H157. Additionally, the results revealed that overexpression of miR­218 could induce XWLC­05 and NCI­H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR­218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B­cell lymphoma 2 (BCL­2) and BMI1 proto­oncogene, polycomb ring finger (BMI­1) at the mRNA and protein level in XWLC­05 and NCI­H157 cell lines. However, we did not observe any remarkable difference in the roles of miR­218 and miR­218­mediated regulation of BCL­2, BMI­1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR­218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL­2 and BMI­1 in Xuanwei lung cancer. The results demonstrated that miR­218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR­218 may be a novel approach for the treatment of Xuanwei lung cancer.