An immune sandwich electrochemical biosensor based on triple-modified zirconium derivatives for detection of CD146 in serum.

CD146, also known as melanoma cell adhesion molecule (MCAM), is overexpressed in various cancer patients, making it a valuable predictor for early diagnosis. In this work, an immune sandwich electrochemical biosensor is proposed for sensitive and non-invasive quantitative detection of CD146 in serum. Zirconium-based MOF (UIO-66) was modified by simultaneous copper atom doping, in situ growth carbon-based support and physical embedding of platinum nanoparticles (PtNPs). Triple-modified Cu-UIO-66@SWCNT/PtNPs nanocomposites with high stability and excellent electrochemical properties, serve as surface modification materials for glassy carbon electrodes. Anti-CD146 antibody (Ab1) was grafted onto the electrode surface via Pt-S bond. Meanwhile, the secondary antibody (Ab2) was conjugated with silver nanoparticles (AgNPs) to cooperate for CD146 capture and achieve secondary electrical signal amplification. Under optimal conditions, square wave voltammetry was employed to determine CD146 in the concentration range of 10-9-10-4 mg/mL and a limit of detection of 12 fg/mL was obtained. Finally, it was successfully applied to the analysis of CD146 in lung and liver cancer patients' serum samples.

[Different calcium ion concentrations affect epithelial mesenchymal transformation of human peritoneal mesothelial cells via endoplasmic reticulum stress].

OBJECTIVE: To study the effects of different calcium ion concentrations on epithelial mesenchymal transformation (EMT) of human peritoneal mesothelial cell (HPMC) via endoplasmic reticulum stress (ERS). METHODS: HPMC cell line HMrSV5 was cultured in vitro and treated in groups. The cells in the control group, high calcium group 1, and high calcium group 2 were treated with medium containing calcium ion concentrations of 1.25, 1.75, and 2.25 mmol/L, respectively. The solvent control group was treated with medium containing 1.25 mmol/L physiological calcium ion concentration and 0.1% dimethyl sulfoxide (DMSO), the high calcium+solvent group was treated with medium containing 2.25 mmol/L calcium ion concentration and 0.1% DMSO, the high calcium+4-phenylbutyric acid (4-PBA) group was treated with medium containing 2.25 mmol/L calcium ion concentration and 1 mmol/L ERS inhibitor 4-PBA, and each group was treated for 48 hours. Morphological changes of cells in each group were observed under light microscope. The expressions of epithelial cell phenotype marker zonula occluden-1 (ZO-1) and mesenchymal cell phenotype marker α-smooth muscle actin (α-SMA) in the cells were observed by immunofluorescence staining. The expressions of EMT marker genes E-cadherin, ZO-1, α-SMA and Vimentin were detected by fluorescence quantitative polymerase chain reaction (PCR). The expressions of ERS marker proteins phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), transcription activating factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by Western blotting. RESULTS: Compared with the control group, the morphology of HMrSV5 cells became slender and fibrotic, the fluorescence intensity of ZO-1 increased, and the fluorescence intensity of α-SMA decreased in high calcium 1 and high calcium 2 groups, indicating that the cells transformed from epithelial cells to mesenchyme cells. The mRNA expressions of E-cadherin and ZO-1 were significantly decreased, while the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly increased, moreover, the expressions of the above marker genes or proteins in the high calcium 2 group was more obvious than those in the high calcium 1 group [E-cadherin mRNA (2-ΔΔCt): 0.53±0.05 vs. 0.75±0.09, ZO-1 mRNA (2-ΔΔCt): 0.42±0.06 vs. 0.69±0.06, α-SMA mRNA (2-ΔΔCt): 1.81±0.16 vs. 1.32±0.14, Vimentin mRNA (2-ΔΔCt): 2.05±0.22 vs. 1.48±0.16, p-PERK protein (p-PERK/ß-actin): 0.81±0.09 vs. 0.59±0.06, p-eIF2α protein (p-eIF2α/ß-actin): 0.87±0.10 vs. 0.50±0.06, ATF4 protein (ATF4/ß-actin): 0.93±0.10 vs. 0.72±0.06, CHOP protein (CHOP/ß-actin): 0.79±0.09 vs. 0.46±0.04, all P < 0.05]. Compared with the solvent control group, the morphological changes of cells, the expressions of EMT marker genes and ERS marker proteins after high calcium ion concentration of 2.25 mmol/L were consistent with those in the high calcium 2 group than control group. Compared with the high calcium+solvent group, the cell morphology recovered the characteristics of polygonal and pebble-like epithelial cells in the high calcium+4-PBA group, the fluorescence intensity of ZO-1 increased, the fluorescence intensity of α-SMA decreased, and the mRNA expressions of E-cadherin and ZO-1 in the cells were significantly increased [E-cadherin mRNA (2-ΔΔCt): 0.86±0.09 vs. 0.57±0.04, ZO-1 mRNA (2-ΔΔCt): 0.81±0.06 vs. 0.48±0.05, both P < 0.05], the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly decreased [α-SMA mRNA (2-ΔΔCt): 1.21±0.13 vs. 1.77±0.15, Vimentin mRNA (2-ΔΔCt): 1.30±0.14 vs. 1.94±0.20, p-PERK protein (p-PERK/ß-actin): 0.38±0.04 vs. 0.92±0.11, p-eIF2α protein (p-eIF2α/ß-actin): 0.34±0.05 vs. 1.05±0.13, ATF4 protein (ATF4/ß-actin): 0.57±0.06 vs. 0.97±0.11, CHOP protein (CHOP/ß-actin): 0.51±0.04 vs. 0.90±0.12, all P < 0.05]. CONCLUSIONS: High calcium ion concentrations of 1.75 mmol/L and 2.25 mmol/L promote EMT of HPMC via activating ERS.

Exit wave function reconstruction from two defocus images using neural network.

Wave function reconstruction from one or two defocus images is promising for live atomic resolution imaging in transmission electron microscopy. However, a robust and accurate reconstruction method we still need more attention. Here, we present a neural-network-based wave function reconstruction method, EWR-NN, that enables accurate wave function reconstruction from only two defocus images. Results from both simulated and two different experimental defocus series show that the EWR-NN method has better performance than the widely-used iterative wave function reconstruction (IWFR) method. Influence of image number, defocus deviation, residual image shifts and noise level were considered to validate the performance of EWR-NN under practical conditions. It is seen that these factors will not influence the arrangement of atom columns in the reconstructed phase images, while they can alter the absolute values of all-atom columns and degrade the contrast of the phase images.

A GPU-based computational framework that bridges neuron simulation and artificial intelligence.

Biophysically detailed multi-compartment models are powerful tools to explore computational principles of the brain and also serve as a theoretical framework to generate algorithms for artificial intelligence (AI) systems. However, the expensive computational cost severely limits the applications in both the neuroscience and AI fields. The major bottleneck during simulating detailed compartment models is the ability of a simulator to solve large systems of linear equations. Here, we present a novel Dendritic Hierarchical Scheduling (DHS) method to markedly accelerate such a process. We theoretically prove that the DHS implementation is computationally optimal and accurate. This GPU-based method performs with 2-3 orders of magnitude higher speed than that of the classic serial Hines method in the conventional CPU platform. We build a DeepDendrite framework, which integrates the DHS method and the GPU computing engine of the NEURON simulator and demonstrate applications of DeepDendrite in neuroscience tasks. We investigate how spatial patterns of spine inputs affect neuronal excitability in a detailed human pyramidal neuron model with 25,000 spines. Furthermore, we provide a brief discussion on the potential of DeepDendrite for AI, specifically highlighting its ability to enable the efficient training of biophysically detailed models in typical image classification tasks.

CSF-Glioma: A Causal Segmentation Framework for Accurate Grading and Subregion Identification of Gliomas.

Deep networks have shown strong performance in glioma grading; however, interpreting their decisions remains challenging due to glioma heterogeneity. To address these challenges, the proposed solution is the Causal Segmentation Framework (CSF). This framework aims to accurately predict high- and low-grade gliomas while simultaneously highlighting key subregions. Our framework utilizes a shrinkage segmentation method to identify subregions containing essential decision information. Moreover, we introduce a glioma grading module that combines deep learning and traditional approaches for precise grading. Our proposed model achieves the best performance among all models, with an AUC of 96.14%, an F1 score of 93.74%, an accuracy of 91.04%, a sensitivity of 91.83%, and a specificity of 88.88%. Additionally, our model exhibits efficient resource utilization, completing predictions within 2.31s and occupying only 0.12 GB of memory during the test phase. Furthermore, our approach provides clear and specific visualizations of key subregions, surpassing other methods in terms of interpretability. In conclusion, the Causal Segmentation Framework (CSF) demonstrates its effectiveness at accurately predicting glioma grades and identifying key subregions. The inclusion of causality in the CSF model enhances the reliability and accuracy of preoperative decision-making for gliomas. The interpretable results provided by the CSF model can assist clinicians in their assessment and treatment planning.

An Incremental Broad-Learning-System-Based Approach for Tremor Attenuation for Robot Tele-Operation.

The existence of the physiological tremor of the human hand significantly affects the application of tele-operation systems in performing high-precision tasks, such as tele-surgery, and currently, the process of effectively eliminating the physiological tremor has been an important yet challenging research topic in the tele-operation robot field. Some scholars propose using deep learning algorithms to solve this problem, but a large number of hyperparameters lead to a slow training speed. Later, the support-vector-machine-based methods have been applied to solve the problem, thereby effectively canceling tremors. However, these methods may lose the prediction accuracy, because learning energy cannot be accurately assigned. Therefore, in this paper, we propose a broad-learning-system-based tremor filter, which integrates a series of incremental learning algorithms to achieve fast remodeling and reach the desired performance. Note that the broad-learning-system-based filter has a fast learning rate while ensuring the accuracy due to its simple and novel network structure. Unlike other algorithms, it uses incremental learning algorithms to constantly update network parameters during training, and it stops learning when the error converges to zero. By focusing on the control performance of the slave robot, a sliding mode control approach has been used to improve the performance of closed-loop systems. In simulation experiments, the results demonstrated the feasibility of our proposed method.

Cushing syndrome caused by an ectopic ACTH-producing pituitary adenoma of the clivus region: A rare case report and literature review.

RATIONALE: Ectopic ACTH-producing pituitary adenoma (EAPA) of the clivus region is extraordinarily infrequent condition and merely a few reports have been reported to date. PATIENT CONCERNS: The patient was a 53-year-old woman who presented with Cushing-like appearances and a soft tissue mass in the clivus region. DIAGNOSES: The final diagnosis of clivus region EAPA was established by clinical, radiological and histopathological findings. INTERVENTIONS: The patient underwent gross total clivus tumor resection via transsphenoidal endoscopy. OUTCOMES: Half a year after surgery, the patient Cushing-like clinical manifestations improved significantly, and urinary free cortisol and serum adrenocorticotropin (ACTH) returned to normal. LESSONS: Given the extreme scarcity of these tumors and their unique clinical presentations, it may be possible to misdiagnose and delayed treatment. Accordingly, it is especially crucial to summarize such lesions through our present case and review the literature for their precise diagnosis and the selection of optimal treatment strategies.

Gut-associated Lymphoid Tissue/Dome-Type Carcinoma of the Colon: A Rare Case Report With Review of the Literature.

Gut-associated lymphoid tissue (GALT) carcinoma, also termed dome-type carcinoma, is an infrequent distinctive subtype of colorectal adenocarcinoma and only 18 cases have been reported in the English medical literature. These tumors have unique clinicopathological features and are considered to have a low malignant potential with favorable prognosis. Herein, we described a case of a 49-year-old male with intermittent hematochezia for 2 years. Colonoscopy revealed a sessile broad-based polyp of approximately 20 mm × 17 mm in the sigmoid colon 260 mm away from the anus, with a slightly hyperemic surface. Histologically, this lesion showed typical GALT carcinoma. The patient was followed up for one and a half year and he did not experience any discomfort, such as abdominal pain or hematochezia, and no tumor recurrence occurred. Moreover, we reviewed the literature, summarized the clinicopathological features of GALT carcinoma, and highlighted its pathological differential diagnosis to further explore this infrequent type of colorectal adenocarcinoma.

Integrated Bioinformatics Analysis for the Screening of Hub Genes and Therapeutic Drugs in Hepatocellular Carcinoma.

BACKGROUND: Liver cancer is a major medical problem because of its high morbidity and mortality. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Currently, the mechanism of HCC is unclear, and the prognosis is poor with limited treatment. OBJECTIVE: The purpose of this study is to identify hub genes and potential therapeutic drugs for HCC. METHODS: We used the GEO2R algorithm to analyze the differential expression of each gene in 4 gene expression profiles (GSE101685, GSE62232, GSE46408, and GSE45627) between HCC and normal hepatic tissues. Next, we screened out the differentially expressed genes (DEGs) by corresponding calculation data according to adjusted P-value < 0.05 and | log fold change (FC) | > 1.0. Subsequently, we used the DAVID software to analyze the DEGs by GO and KEGG enrichment analysis. Then, we carried out the protein-protein interaction (PPI) network analysis of DEGs using the STRING tool, and the PPI network was constructed by Cytoscape software. MCODE plugin was used for module analysis, and the hub genes were screened out by the Cyto- Hubba plugin. Meanwhile, we used The Kaplan-Meier plotter, GEPIA2 and HPA databases to exert survival analysis and verify the expression alternation of hub genes. Furthermore, we used ENCORI, TargetScan, miRDB and miRWalk database to predict the upstream regulated miRNA of hub genes and construct a miRNA-hub genes network by Cytoscape software. Finally, we selected potential therapeutic drugs for HCC through DGIdb databases. RESULTS: A total of 415 DEGs were screened in HCC, including 196 up-regulated DEGs and 219 down-regulated DEGs. The results of KEGG pathway analysis suggested that the up-regulated DEGs can regulate the cell cycle, and DNA replication signal pathway, while the down-regulated DEGs were associated with metabolic pathways. In this study, we identified 11 hub genes (AURKA, BUB1B, TOP2A, MAD2L1, CCNA2, CCNB1, BUB1, KIF11, CDK1, CCNB2 and TPX2), which were independent risk factors of HCCand all up-regulated DEGs. We verified the expression difference of hub genes through the GEPIA2 and HPA database, which was consistent with the results of GEO data. We found that those hub genes were mutations in HCC according to the cBioPortal database. Finally, we used the DGIdb database to select 32 potential therapeutic targeting drugs for hub genes. CONCLUSION: In summary, our study provided a new perspective for researching the molecular mechanism of HCC. Hub genes, miRNAs, and candidate drugs provide a new direction for the early diagnosis and treatment of HCC.

Sinonasal mucosal melanoma with smooth muscle differentiation: a potential pathological diagnostic pitfall.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a rare malignant melanoma originating from melanocytes derived from multipotent neural crest cells. Its incidence accounts for less than 1 % of all malignant melanomas, with five-year survival rate about 25 %. Occasionally, it is incredibly formidable to make a compelling diagnosis when malignant melanoma with other diverse differentiation. CASE PRESENTATION: Herein, we presented a 54-year-old male case of SNMM with smooth muscle differentiation, defined by histopathology and positive immunostaining for the smooth muscle specific markers of a-SMA, H-caldesmon, calponin and Desmin, as well as specific melanocyte markers of HMB-45, Melan-A, SOX10, and PNL2. CONCLUSIONS: Mucosal melanoma with smooth muscle differentiation is remarkably infrequent, and reported only 4 cases to date. It would be a potential pathological diagnostic pitfall. It is important to understand this variation of malignant melanoma for avoiding misdiagnosis.

A theoretical model reveals specialized synaptic depressions and temporal frequency tuning in retinal parallel channels.

In the Outer Plexiform Layer of a retina, a cone pedicle provides synaptic inputs for multiple cone bipolar cell (CBC) subtypes so that each subtype formats a parallelized processing channel to filter visual features from the environment. Due to the diversity of short-term depressions among cone-CBC contacts, these channels have different temporal frequency tunings. Here, we propose a theoretical model based on the hierarchy Linear-Nonlinear-Synapse framework to link the synaptic depression and the neural activities of the cone-CBC circuit. The model successfully captures various frequency tunings of subtype-specialized channels and infers synaptic depression recovery time constants inside circuits. Furthermore, the model can predict frequency-tuning behaviors based on synaptic activities. With the prediction of region-specialized UV cone parallel channels, we suggest the acute zone in the zebrafish retina supports detecting light-off events at high temporal frequencies.

Coexistence of primary pulmonary meningioma and metastatic papillary renal cell carcinoma of the lung: A rare case report with review of the literature.

RATIONALE: Primary pulmonary meningioma (PPM) is extremely rare tumor and only a few reports have been reported to date. PPM may be overlooked when it coexists with other types of tumors in the lung. It is essential to have a knowledge of the clinicopathological features of PPM and to recognize this rare coexistence. PATIENT CONCERNS: A 57-year-old male underwent surgery for papillary renal cell carcinoma, when 2 pulmonary nodules were detected using chest computed tomography. DIAGNOSIS: The coexistence of benign PPM and metastatic papillary renal cell carcinoma was histologically confirmed. INTERVENTIONS: A lobectomy was performed. OUTCOMES: The patient recovered well after surgery and was discharged on postoperative day 4. LESSONS: Duo to the rarity of PPM, it is easily overlooked, especially when it coexists with other tumors in the lung. The possibility of PPM needs to be taken into account when diagnosing pulmonary nodules in clinical practice.

Identifying Potential Tumor Antigens and Antigens-Related Subtypes in Hepatocellular Carcinoma for mRNA Vaccine Development.

Background: The mRNA vaccine has become a promising platform for cancer therapy. Lots of studies have been focusing on discovering novel potent cancer-associated antigens to develop mRNA vaccines against cancers. Besides, immunotyping shows the immune status, and immune microenvironment of immunotyping is related with therapeutic reaction. However, potential antigens for mRNA vaccines and immunotyping of liver hepatocellular carcinoma (LIHC) remain far from being understood. Methods: In this study, we collected gene expression data and clinical information data from ICGC and TCGA databases. Using GEPIA2, we calculated differential expression genes and prognostic indices. We applied TIMER to calculate the correlation coefficient between immune infiltrating cells and each gene. Consensus cluster was used for immunotyping of LIHC. Results: We uncovered four most potential candidates including PES1, MCM3, PPM1G, and KPNA2, which were all related with antigen-presenting cell (APC) infiltration and poor survival in LIHC in two independent datasets. Furthermore, three immune-related subtypes (IS1-IS3) of LIHC were identified. All these results were validated in two independent datasets. Furthermore, we validated our results in vitro. Conclusions: The above candidates will be expected to be potential antigen genes for developing anti-LIHC mRNA vaccine, and furthermore, patients with IS2 and IS3 tumors are supposed to be appropriate for mRNA vaccine in LIHC.

Total Syntheses of the Structures Assigned to the Marine Natural Products Orthoscuticellines A-E.

The readily prepared and vinylated ß-carboline 11 has been converted over one or two steps into compounds 1-5, the structures assigned to the recently reported marine natural products orthoscuticellines A-E. The spectral data recorded on the synthetically derived compounds are fully consistent with the assigned structures and, on making allowances for variations in the pH of the medium in which the spectra of the natural products were recorded, it is concluded that the structures assigned to orthoscuticellines A-E are most likely correct. Certainly, the calculated 13C NMR spectra of the α-, γ-, and δ-carboline isomers of compounds 1-5 suggest that orthoscuticellines A-E do incorporate the assigned ß-carboline core.

Ameliorating Inflammation in Insulin-resistant Rat Adipose Tissue with Abdominal Massage Regulates SIRT1/NF-κB Signaling.

It was the aim of this study to determine whether abdominal massage reverses high-fat diet-induced insulin resistance compared with RSV treatment. A total of sixty male Sprague-Dawley rats were randomly placed in one of four groups:the non-fat diet (NFD), the high-fat diet (HFD), the HFD with abdominal massage (HFD+ AM), and the HFD plus resveratrol (HFD+ RSV). For eight weeks, rats were fed high-fat diets to create insulin resistance, followed by six weeks of either AM or RSV. Molecular mechanisms of adipogenesis and cytokine production in rats with high-fat diets were investigated. The model rat adipose tissue showed significant improvements in obesity, glucose intolerance, and the accumulation of lipid in the body [the total cholesterol level (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], metabolic effects of glucose [The fasting blood glucose (FBG), Fasting insulin levels (FINS)], inflammatory status [interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α, C-reactive protein (CRP)], and macrophage polarization after AM or RSV treatment. Further, AM increased SIRT1/NF-κB signaling in rat adipose tissue. Accordingly, in rat adipose tissue, our results indicate that AM regulates the secretion of proinflammatory cytokines, blood sugar levels, and related signaling pathways, contributing to improvement of IR, which may serves as a new therapeutic approach for the treatment for IR.

Expeditious Access to Morphinans by Chemical Synthesis.

Morphinans are essential medicines derived entirely from poppy supply chains rendered increasingly volatile by climate change. Here, we report a seven-step, asymmetric chemical synthesis of (-)-codeine from simple materials that requires a total combined reaction time of fewer than 24 hours. The efficiency of our approach arises from a double-Heck cyclization reaction that generates two rings and two contiguous stereogenic carbon centres in the one pot. A subsequent photo-redox hydroamination protocol provides a novel, atom-economical means for assembling the piperidine D-ring of codeine. Simple modifications to the closing stages of our sequence offer effective access to pharmacologically valuable derivatives of N-demethyl codeine. Our work highlights the capacity for contemporary, stand-alone chemical synthesis regimes to diversify access to essential opiate medicines.

IDART: An Improved Discrete Tomography Algorithm for Reconstructing Images With Multiple Gray Levels.

The discrete algebraic reconstruction technique has many advantages in computed tomography and electron tomography. However, the number of gray levels and the absolute gray values that should be known in advance are typically not available in experiments especially when there are many gray levels in the image. In this paper, we report an automatic discrete tomography reconstruction algorithm to improve its feasibility in practice, without needing to know these two parameters. In our algorithm, the number of gray levels is estimated by labeling the connected components in the tomogram and the absolute values of them are determined by the modal value of each domain. The proposed algorithm was extensively validated on both simulated and experimental datasets. The results show that our algorithm can accurately recover not only the morphology but also the gray levels of the interested objects, even in the images with multiple gray levels. It is demonstrated that the presented algorithm is robust for eliminating missing wedge artifacts and tolerable for noisy data.

Integrated analysis of ceRNA network reveals potential prognostic Hint1-related lncRNAs involved in hepatocellular carcinoma progression.

BACKGROUND: Hint1 is a novel tumor suppressor gene, and inactivation of its expression is closely associated with the carcinogenesis of a variety of malignancies. The effects of Hint1 deficiency on the competing endogenous RNA (ceRNA) regulatory network in the context of HCC remains to be fully characterized. This study aims to explore Hint1-related hub lncRNAs in HCC and to establish a reliable prognostic model for HCC patients based on these hub lncRNAs. METHODS: lncRNA + mRNA microarray was used to identify differentially expressed (DE) lncRNAs and mRNAs in Huh7 cells before and after Hint1 knockdown. A Hint1-related ceRNA network was mapped by bioinformation technology. The DEmRNAs in the network were analyzed via GO and KEGG enrichment analyses. Hub DElncRNAs associated with HCC patient prognosis were then detected through univariate and multivariate Cox regression analyses and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, and nomograms. We also utilized Kaplan-Meier curves to validate the relationship between hub lncRNAs and the overall survival (OS) of HCC patients. Finally, A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was mapped. RESULTS: We identified 417 differentially expressed DElncRNAs and 2096 DEmRNAs in Huh7 cells before and after Hint1 knockdown. Three hub DElncRNAs (LINC00324, SNHG3, and DIO3OS) in the Hint1-associated ceRNA network were screened out using univariate and multivariate Cox regression analyses. A hepatocellular carcinoma (HCC) prognostic risk-scoring model and nomogram were constructed using these three hub lncRNAs, and it was confirmed that the risk score of the model could be used as an independent predictor of HCC prognosis. A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was also mapped. CONCLUSION: We constructed a reliable prognostic model for HCC patients based on three Hint1-related hub lncRNAs, and we believe these three hub lncRNAs may play critical roles in hepatocarcinogenesis, and progression.

Silver-Promoted Radical Ring-Opening/Pyridylation of Cyclobutanols with N-Methoxypyridinium Salts.

The silver-promoted reaction of tertiary cyclobutanols with N-methoxypyridinium salts enables the efficient synthesis of a range of C2-substituted pyridines. The overall process likely occurs by ring-opening (via ß-scission) of the cyclobutoxy radical to generate the corresponding γ-keto alkyl radical that itself adds to the pyridinium salt. A wide range of tertiary cyclobutanols and N-methoxypyridinium salts are compatible with the reaction conditions.

Synthesis of Various Bridged Ring Systems via Rhodium-Catalyzed Bridged (3+2) Cycloadditions.

Here, we describe the rhodium-catalyzed bridged (3+2) cycloaddition cascade reactions of N-sulfonyl-1,2,3-triazoles, which allowed the efficient diastereoselective construction of various functionalized and synthetically challenging bridged ring systems. This simple, direct transformation had a broad substrate scope and excellent functional group tolerance. The highly strained polycyclic bicyclo[2.2.2]octa[b]indole core of fruticosine was synthesized efficiently using this methodology.