Potential Role of MAP3K14 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis and Validation.

According to reports, MAP3K14 is considered an oncogene and is aberrantly expressed in various types of tumor cells. Its abnormal expression is closely associated with the occurrence and progression of various cancers. MAP3K14 also plays a significant role in the development of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma and its connection to tumor stem cells. The prognostic value of MAP3K14 in HCC, as well as its potential functions and roles, requires further elucidation. We evaluated the potential role of MAP3K14 in HCC based on data mining from a range of public databases. The bioinformatics analysis of TCGA, GEO, TIMER, cBioportal, Kaplan-Meier plotter, MethSurv, ENCORI and CellMiner databases was carried out. The expression of MAP3K14 protein in HCC was detected by immunohistochemical method. The mRNA and protein expression levels of MAP3K14 in tumor tissues were higher than those in normal tissues (p < 0.05). The expression of MAP3K14 was correlated with Pathologic T stage (p=0.026), Pathologic stage (p=0.032), Tumor status (p=0.024) and AFP (p=0.002). HCC patients with high expression of MAP3K14 had poor overall survival (OS), progression free survival (PFS) and recurrence free survival (RFS). Multivariate Cox regression analysis showed that the Pathologic stage (p < 0.001) and MAP3K14 expression levels (p < 0.05) is an independent prognostic factor affecting the survival of patients with liver cancer. GO/KEGG analysis suggested that key biological processes (PI3K-Akt signaling pathway) may be the mechanism promoting HCC development. In addition, MAP3K14 was significantly correlated with the infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p < 0.05). MAP3K14 is up-regulated in HCC and is closely related to the prognosis of HCC patients. MAP3K14 may serve as a potential biomarker for poor prognosis of HCC.

Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

The dysregulation of biliary tract microflora is closely related to primary choledocholithiasis: a multicenter study.

Bile microecology changes play an important role in the occurrence and development of choledocholithiasis. At present, there is no clear report on the difference of bile microecology between asymptomatic patients with gallbladder polyps and choledocholithiasis. This study compared bile microecology between gallbladder polyp patients and patients with choledocholithiasis to identify risk factors for primary choledocholithiasis. This study was conducted in 3 hospitals in different regions of China. Bile samples from 26 patients with gallbladder polyps and 31 patients with choledocholithiasis were collected by laparoscopic cholecystectomy and endoscopic retrograde choledocholithiasis cholangiography (ERCP), respectively. The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. The α-diversity of bile microecological colonies was similar between gallbladder polyp and choledocholithiasis, but the ß-diversity was different. Firmicutes, Proteobacteri, Bacteroidota and Actinobacteriota are the most common phyla in the gallbladder polyp group and choledocholithiasis group. However, compared with the gallbladder polyp patients, the abundance of Actinobacteriota has significantly lower in the choledocholithiasis group. At the genera level, the abundance of a variety of bacteria varies between the two groups, and Enterococcus was significantly elevated in choledocholithiasis group. In addition, bile biofilm formation-Pseudomonas aeruginosa was more metabolically active in the choledocholithiasis group, which was closely related to stone formation. The analysis of metabolites showed that a variety of metabolites decreased in the choledocholithiasis group, and the concentration of beta-muricholic acid decreased most significantly. For the first time, our study compared the bile of gallbladder polyp patients with patients with choledocholithiasis, and suggested that the change in the abundance of Actinobacteriota and Enterococcus were closely related to choledocholithiasis. The role of Pseudomonas aeruginosa biofilm in the formation of choledocholithiasis was discovered for the first time, and some prevention schemes for choledocholithiasis were discussed, which has important biological and medical significance.

The enhancement of astaxanthin production in Phaffia rhodozyma through a synergistic melatonin treatment and zinc finger transcription factor gene overexpression.

Astaxanthin has multiple physiological functions and is applied widely. The yeast Phaffia rhodozyma is an ideal source of microbial astaxanthin. However, the stress conditions beneficial for astaxanthin synthesis often inhibit cell growth, leading to low productivity of astaxanthin in this yeast. In this study, 1 mg/L melatonin (MT) could increase the biomass, astaxanthin content, and yield in P. rhodozyma by 21.9, 93.9, and 139.1%, reaching 6.9 g/L, 0.3 mg/g DCW, and 2.2 mg/L, respectively. An RNA-seq-based transcriptomic analysis showed that MT could disturb the transcriptomic profile of P. rhodozyma cell. Furthermore, differentially expressed gene (DEG) analysis show that the genes induced or inhibited significantly by MT were mainly involved in astaxanthin synthesis, metabolite metabolism, substrate transportation, anti-stress, signal transduction, and transcription factor. A mechanism of MT regulating astaxanthin synthesis was proposed in this study. The mechanism is that MT entering the cell interacts with components of various signaling pathways or directly regulates their transcription levels. The altered signals are then transmitted to the transcription factors, which can regulate the expressions of a series of downstream genes as the DEGs. A zinc finger transcription factor gene (ZFTF), one of the most upregulated DEGs, induced by MT was selected to be overexpressed in P. rhodozyma. It was found that the biomass and astaxanthin synthesis of the transformant were further increased compared with those in MT-treatment condition. Combining MT-treatment and ZFTF overexpression in P. rhodozyma, the biomass, astaxanthin content, and yield were 8.6 g/L, 0.6 mg/g DCW, and 4.8 mg/L and increased by 52.1, 233.3, and 399.7% than those in the WT strain under MT-free condition. In this study, the synthesis and regulation theory of astaxanthin is deepened, and an efficient dual strategy for industrial production of microbial astaxanthin is proposed.

Correlation of Differentially Expressed lncRNAs with Intestinal Flora Imbalance, Small Intestinal Permeability, and Glucose Uptake in T2DM Mice.

Diabetes is a major global health concern. This study aimed to investigate the correlation between differentially expressed lncRNAs in mice with type 2 diabetes mellitus (T2DM) and alterations in the intestinal flora and intestinal pathology. A T2DM mouse model was constructed by feeding mice a high-fat diet. Serum fat metabolism-related indices and insulin levels were biochemically detected. Serum inflammatory factors (IL-1ß, IL-6, TNF-α, IL-10) and endotoxin (LPS) were measured by ELISA. Histopathological changes in the small intestines of mice were observed by HE. The short-chain fatty acid (SCFA) content was analyzed using GC-MS. Analysis of altered intestinal flora in T2DM mice was performed using a 16sRNA sequencing assay. Differences in lncRNA expression profiles in small intestinal tissues were analyzed using RNA-seq assays. Spearman's correlation analysis was used to correlate the expression of candidate lncRNAs with changes in differential gut flora. Spearman's correlation analysis was used to analyze the correlation between the expression of candidate differentially expressed lncRNAs, small intestinal permeability, and glucose absorption. We found that serum levels of LPS, BUN, Scr, TC, TG, LDL-C, IL-1ß, IL-6, and TNF-α were elevated and levels of HDL-C, insulin, and IL-10 were decreased in T2DM mice. The ileal enterochromes of T2DM mice were disorganized and broken, the number of enterochromes was reduced, the local epithelial cells were necrotic, and the plasma membrane layer was locally absent. In addition, the protein expression of ZO-1 and occludin was decreased, and the protein expression of SGLT-1 and GLUT-2 was elevated in the model group compared to the control group. The levels of Acetic acid, Propionic acid and Butyric acid were decreased and the levels of Isobutyric acid and Isovaleric acid were increased, the abundance of beneficial bacteria was decreased and the abundance of harmful bacteria was increased in the feces of T2DM mice. RNA-seq identified nine differentially expressed lncRNAs (LINC00675, Gm33838, Gm11655, LOC6613926, LOC6613788, LOC6613791, LOC6613795, Arhgap27os3, and A330023F24Rik). In addition, we found significant correlations between differentially expressed lncRNAs and a variety of intestinal flora, as well as between small intestinal permeability and glucose absorption. A significant correlation was observed between differentially expressed lncRNAs in the intestinal tissues of T2DM mice and intestinal flora imbalance, small intestinal permeability, and glucose absorption.

Mirizzi syndrome: Problems and strategies.

Mirizzi syndrome is a serious complication of gallstone disease. It is caused by the impacted stones in the gallbladder neck or cystic duct. One of the features of Mirizzi syndrome is severe inflammation or dense fibrosis at the Calot's triangle. In our clinical practice, bile duct, branches of right hepatic artery and right portal vein clinging to gallbladder infundibulum are often observed due to gallbladder infundibulum adhered to right hepatic hilum. The intraoperative damage of branches of right hepatic artery occurs more easily than that of bile duct, all of which are hidden pitfalls for surgeons. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferable tools for the diagnosis of Mirizzi syndrome. Anterograde cholecystectomy in Mirizzi syndrome is easy to damage branches of right hepatic artery and bile duct due to gallbladder infundibulum adhered to right hepatic hilum. Subtotal cholecystectomy is an easy, safe and definitive approach to Mirizzi syndrome. When combined with the application of ERCP, a laparoscopic management of Mirizzi syndrome by well-trained surgeons is feasible and safe. The objective of this review was to highlight its existing problems: (1) low preoperative diagnostic rate, (2) easy to damage bile duct and branches of right hepatic artery, and (3) high concomitant gallbladder carcinoma. Meanwhile, the review aimed to discuss the possible therapeutic strategies: (1) to enhance its preoperative recognition by imaging findings, and (2) to avoid potential pitfalls during surgery.

Ring geometric effect on the performance of AlGaN-based deep-ultraviolet light-emitting diodes.

In this study, we fabricated and characterized various parallel flip-chip AlGaN-based deep-ultraviolet (DUV) micro-ring LEDs, including changes in ring dimensions as well as the p-GaN-removed region widths at the outer micro-ring, respectively (PRM LEDs). It is revealed that the LED chips with smaller mesa withstand higher current density and deliver considerably higher light output power density (LOPD), under the same proportion of the hole to the entire mesa column (before it is etched into ring) within the limits of dimensions. However, as the ring-shaped mesa decreases, the LOPD begins to decline because of etching damage. Subsequently, at the same external diameter, the optical performance of micro-ring LEDs with varied internal diameters is studied. Meanwhile, the influence of different structures on light extraction efficiency (LEE) is studied by employing a two-dimensional (2D)-finite-difference time-domain (FDTD) method. In addition, the expand of the p-GaN-removed region at the outer micro-ring as well as the corresponding effective light emission region have some influence to LOPD. The PRM-23 LED (with an external diameter of 90 µm, an internal diameter of 22 µm, and a p-GaN-removed region width of 8 µm) has an LOPD of 53.36 W/cm2 with a current density of 650 A/cm2, and an external quantum efficiency (EQE) of 6.17% at 5 A/cm2. These experimental observations provide a comprehensive understanding of the optical and electrical performance of DUV micro-LEDs for future applications.

Pan-cancer analysis revealing the multidimensional expression and prognostic and immunologic roles of TGFB1 in cancer.

OBJECTIVE: This study aimed to perform an integrated pan-cancer analysis to characterize the expression patterns, prognostic value, genetic alterations, and immunologic roles of transforming growth factor beta 1 (TGFB1) across diverse human cancer types. METHODS: Bioinformatics analyses were conducted using multiple public databases including The Cancer Genome Atlas, Genotype-Tissue Expression, Clinical Proteomic Tumor Analysis Consortium, TIMER2, GEPIA2, cBioPortal, StringDB, and others. Differential expression, survival, immune correlation, and protein interaction network analyses were performed. RESULTS: TGFB1 was overexpressed in several tumor types compared with that in normal tissues. High TGFB1 expression was associated with an advanced stage and poorer prognosis in certain cancers. TGFB1 mutations occurred in 1.3% of 10,967 cases surveyed. TGFB1 expression correlated with tumor-infiltrating immune cells and immunotherapy-related genes. CONCLUSIONS: This comprehensive multi-omics analysis revealed the complex expression and prognostic landscape of TGFB1 across cancers. TGFB1 is emerging as a potential immunotherapeutic target in certain contexts. Further research should elucidate its multifaceted tumor-promoting and tumor-suppressive mechanisms. Our pan-cancer analysis provides new insights into TGFB1 as a prognostic biomarker and immunotherapeutic target in human cancers, and our findings may guide future preclinical and clinical investigations of TGFB1-directed therapies.

Correction: Stretchable and durable HD-sEMG electrodes for accurate recognition of swallowing activities on complex epidermal surfaces.

[This corrects the article DOI: 10.1038/s41378-023-00591-3.].

Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies. Materials and methods: We performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms. Results: Genetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment. Conclusion: Our findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.

Salicylic acid treatment and overexpression of a novel polyamine transporter gene for astaxanthin production in Phaffia rhodozyma.

Phaffia rhodozyma represents an excellent microbial resource for astaxanthin production. However, the yeast's low astaxanthin productivity poses challenges in scaling up industrial production. Although P. rhodozyma originates from plant material, and phytohormones have demonstrated their effectiveness in stimulating microbial production, there has been limited research on the effects and mechanisms of phytohormones on astaxanthin biosynthesis in P. rhodozyma. In this study, the addition of exogenous salicylic acid (SA) at a concentration as low as 0.5 mg/L significantly enhanced biomass, astaxanthin content, and yield by 20.8%, 95.8% and 135.3% in P. rhodozyma, respectively. Moreover, transcriptomic analysis showed that SA had discernible impact on the gene expression profile of P. rhodozyma cells. Differentially expressed genes (DEGs) in P. rhodozyma cells between the SA-treated and SA-free groups were identified. These genes played crucial roles in various aspects of astaxanthin and its competitive metabolites synthesis, material supply, biomolecule metabolite and transportation, anti-stress response, and global signal transductions. This study proposes a regulatory mechanism for astaxanthin synthesis induced by SA, encompassing the perception and transduction of SA signal, transcription factor-mediated gene expression regulation, and cellular stress responses to SA. Notably, the polyamine transporter gene (PT), identified as an upregulated DEG, was overexpressed in P. rhodozyma to obtain the transformant Prh-PT-006. The biomass, astaxanthin content and yield in this engineered strain could reach 6.6 g/L, 0.35 mg/g DCW and 2.3 mg/L, 24.5%, 143.1% and 199.0% higher than the wild strain at the SA-free condition, respectively. These findings provide valuable insights into potential targets for genetic engineering aimed at achieving high astaxanthin yields, and such advancements hold promise for expediting the industrialization of microbial astaxanthin production.

Safety and Efficacy Analysis of PD-1 Inhibitors in Combination with Gemcitabine Plus Nab-Paclitaxel for Advanced Pancreatic Cancer: A Real-World, Single-Center Study.

Background: Pancreatic cancer is a deadly disease with a low five years survival rate, and chemotherapy remains the standard treatment for advanced cases. However, the efficacy of chemotherapy alone is limited, and there is a need for new treatment options. Recently, immune checkpoint inhibitors (ICIs), particularly programmed death-1 (PD-1) inhibitors, have shown promising results in various cancers, including pancreatic cancer. In this study, we explore the safety and efficacy of PD-1 inhibitors in combination with chemotherapy for advanced pancreatic cancer. Materials and Methods: A retrospective analysis was conducted on clinical data from 27 patients with advanced pancreatic cancer who were administered a combination of anti-PD-1 antibody and gemcitabine plus nab-paclitaxel (GnP) regimen. The study evaluated the safety of the treatment as well as the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: In this study, treatment with a combination of anti-PD-1 antibody and GnP regimen for pancreatic cancer resulted in partial response (PR) for 10 out of 27 (37.04%) patients, stable disease (SD) for 10 (37.04%) patients, and progressive disease (PD) for 7 (25.92%) patients. The study found that the median OS (mOS) for these patients was 16.4 months [standard error (SE) = 1.117, 95% confidence interval (CI) 14.211-18.589], while the median PFS (mPFS) was 6.4 months (SE = 1.217, 95% CI 3.981-8.752). Subgroup analysis revealed that pancreatic cancer patients' Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 vs 1) and treatment cycles (≤6 cycles vs >6 cycles) significantly affected OS and PFS. Patients experienced mostly grade 1-2 adverse events (AEs), which were relieved through clinical treatment. Conclusion: The combination of GnP with anti-PD-1 antibodies shows promise as a potential treatment option for advanced pancreatic cancer.

PPIH gene regulation system and its prognostic significance in hepatocellular carcinoma: a comprehensive analysis.

BACKGROUND: Peptidyl-prolyl isomerase H (PPIH) is a member of the cyclophilin protein family, which functions as a molecular chaperone and is involved in the splicing of pre-mRNA. According to reports, the malignant progression of HCC related to hepatitis B virus (HBV) is tightly associated with RNA-binding proteins. Nevertheless, there is no research on PPIH expression or its function in the occurrence and progression of HCC. RESULTS: We are the first to reveal that the mRNA and protein levels of Ppih are substantially overexpressed in HCC, as the outcomes show. A significant correlation existed between enriched expression of Ppih within HCC and more advanced, poorly differentiated, and TP53-mutated tumors. CONCLUSION: These findings, which suggest that Ppih may serve as a predictive biomarker for people with HCC, serve as a starting point for further investigation into the function of Ppih in the progression of carcinogenesis. METHODS: Accordingly, we utilized clinical samples and bioinformatics analysis to assess Ppih's mRNA, protein expression, and gene regulatory system in HCC. Additionally, Wilcoxon signed-rank testing and logistic regression were utilized to inspect the association between clinicopathological factors and Ppih. Clinical pathological traits linked to overall survival (OS) among HCC patients were examined via TCGA data via Cox regression and the Kaplan-Meier approach. Additionally, via TCGA data collection, gene set enrichment assessment was also conducted.

Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice.

Background: T cell-mediated acute rejection(AR) after heart transplantation(HT) ultimately results in graft failure and is a common indication for secondary transplantation. It's a serious threat to heart transplant recipients. This study aimed to explore the novel lncRNA-miRNA-mRNA networks that contributed to AR in a mouse heart transplantation model. Methods: The donor heart from Babl/C mice was transplanted to C57BL/6 mice with heterotopic implantation to the abdominal cavity. The control group was syngeneic heart transplantation with the same kind of mice donor. The whole-transcriptome sequencing was performed to obtain differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in mouse heart allograft. The biological functions of ceRNA networks was analyzed by GO and KEGG enrichment. Differentially expressed ceRNA involved in programmed cell death were further verified with qRT-PCR testing. Results: Lots of DEmRNAs, DEmiRNAs and DElncRNAs were identified in acute rejection and control after heart transplantation, including up-regulated 4754 DEmRNAs, 1634 DElncRNAs, 182 DEmiRNAs, and down-regulated 4365 DEmRNAs, 1761 DElncRNAs, 132 DEmiRNAs. Based on the ceRNA theory, lncRNA-miRNA-mRNA regulatory networks were constructed in allograft acute rejection response. The functional enrichment analysis indicate that the down-regulated mRNAs are mainly involved in cardiac muscle cell contraction, potassium channel activity, etc. and the up-regulated mRNAs are mainly involved in T cell differentiation and mononuclear cell migration, etc. The KEGG pathway enrichment analysis showed that the down-regulated DEmRNAs were mainly enriched in adrenergic signaling, axon guidance, calcium signaling pathway, etc. The up-regulated DEmRNAs were enriched in the adhesion function, chemokine signaling pathway, apoptosis, etc. Four lncRNA-mediated ceRNA regulatory pathways, Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox, 1700071M16Rik/miR-145a-3p/Themis2, were finally validated. In addition, increased expression of PVT1, 1700071M16Rik, Tox and Themis2 may be considered as potential diagnostic gene biomarkers in AR. Conclusion: We speculated that Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox and 1700071M16Rik/miR-145a-3p/Themis2 interaction pairs may serve as potential biomarkers in AR after HT.

Stretchable and durable HD-sEMG electrodes for accurate recognition of swallowing activities on complex epidermal surfaces.

Surface electromyography (sEMG) is widely used in monitoring human health. Nonetheless, it is challenging to capture high-fidelity sEMG recordings in regions with intricate curved surfaces such as the larynx, because regular sEMG electrodes have stiff structures. In this study, we developed a stretchable, high-density sEMG electrode array via layer-by-layer printing and lamination. The electrode offered a series of excellent human‒machine interface features, including conformal adhesion to the skin, high electron-to-ion conductivity (and thus lower contact impedance), prolonged environmental adaptability to resist water evaporation, and epidermal biocompatibility. This made the electrode more appropriate than commercial electrodes for long-term wearable, high-fidelity sEMG recording devices at complicated skin interfaces. Systematic in vivo studies were used to investigate its ability to classify swallowing activities, which was accomplished with high accuracy by decoding the sEMG signals from the chin via integration with an ear-mounted wearable system and machine learning algorithms. The results demonstrated the clinical feasibility of the system for noninvasive and comfortable recognition of swallowing motions for comfortable dysphagia rehabilitation.

Heat shock protein B7 (HSPB7) inhibits lung adenocarcinoma progression by inhibiting glycolysis.

In the present study, it was aimed to investigate the effects and potential mechanisms of heat shock protein B7 (HSPB7) on lung adenocarcinoma (LUAD). Bioinformatic analysis was performed to explore the association between HSPB7 expression and patients with LUAD. MTT, colony formation, wound healing and Transwell assays were performed to examine the proliferative, migratory and invasive abilities of H1975 and A549 cells. Western blot analysis was conducted to determine the corresponding protein expression. Co­Immunoprecipitation and Chromatin immunoprecipitation assays were carried out to reveal the interaction between HSPB7 and myelodysplastic syndrome 1 and ecotropic viral integration site 1 complex locus (MECOM). In addition, an animal model was conducted by the subcutaneous injection of A549 cells into BALB/c nude mice, and tumor weight and size were measured. HSPB7 was downregulated in LUAD tissues and cells, and its expression level correlated with patient prognosis. Cell functional data revealed that silencing of HSPB7 promoted lung cancer cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT); whereas overexpression of HSPB7 led to the opposite results. Furthermore, bioinformatics analysis showed that HSPB7 inhibited glycolysis. HSPB7 decreased glucose consumption, lactic acid production, and lactate dehydrogenase A, hexokinase 2 and pyruvate kinase muscle isoform 2 protein levels. The results demonstrated that MECOM was a transcription factor of HSPB7. Collectively, these results suggested that HSPB7 is regulated by MECOM, and that HSPB7 attenuates LUAD cell proliferation, migration, invasion and EMT by inhibiting glycolysis.

Advanced hepatocellular carcinoma with MET-amplified contained excellent response to crizotinib: a case report.

Introduction: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Several novel therapeutic strategies have been developed to prolong the survival of patients with advanced HCC. However, therapeutic decision-making biomarkers owing to the extensive heterogeneity of HCC. Next-generation sequencing (NGS) is generally used in treatment decisions to help patients benefit from genome-directed targeting. Case presentation: A 56 year-old male with type-B hepatitis for more than 20 years was admitted to our department and underwent laparoscopic left lateral hepatic lobectomy for hepatocellular carcinoma. Unfortunately, the tumor recurred 1 year later. Despite multiple treatments, the tumor continued to progress and invaded the patient's 5th thoracic vertebras, leading to hypoesthesia and hypokinesia below the nipple line plane 2 years later. NGS revealed MET amplification, and crizotinib, an inhibitor of MET, was recommended. After administration for a month, tumor marker levels decreased, and the tumor shrunk. The patient has remained in remission since that time. Conclusions: We report that a patient with high MET amplification benefited from its inhibitor, which was recommended by NGS. This indicates the potential clinical decision support value of NGS and the satisfactory effect of MET inhibitors.

Graph-EAM: An Interpretable and Efficient Graph Neural Network Potential Framework.

The development of deep learning interatomic potentials has enabled efficient and accurate computations in quantum chemistry and materials science, circumventing computationally expensive ab initio calculations. However, the huge number of learnable parameters in deep learning models and their complex architectures hinder physical interpretability and affect the robustness of the derived potential. In this work, we propose graph-EAM, a lightweight graph neural network (GNN) inspired by the empirical embedded atom method to model the interatomic potential of single-element structures. Four material systems: platinum, niobium, silicon, and amorphous-carbon, for which quantum simulation data sets are publicly available, are examined to demonstrate that graph-EAM can achieve high energy and force prediction accuracy─comparable or better than existing state-of-the-art machine learning models─with much fewer parameters. It is also shown that the explicit inclusion of the angular information via three-body atomic density increases the prediction accuracy. The accuracy and efficiency of potentials obtained from graph-EAM can help accelerate the molecular dynamics simulation.