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.

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.

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.

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.

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.

Visible-Light-Induced ortho-Selective Migration on Pyridyl Ring: Trifluoromethylative Pyridylation of Unactivated Alkenes.

The photocatalyzed ortho-selective migration on a pyridyl ring has been achieved for the site-selective trifluoromethylative pyridylation of unactivated alkenes. The overall process is initiated by the selective addition of a CF3 radical to the alkene to provide a nucleophilic alkyl radical intermediate, which enables an intramolecular endo addition exclusively to the ortho-position of the pyridinium salt. Both secondary and tertiary alkyl radicals are well-suited for addition to the C2-position of pyridinium salts to ultimately provide synthetically valuable C2-fluoroalkyl functionalized pyridines. Moreover, the method was successfully applied to the reaction with P-centered radicals. The utility of this transformation was further demonstrated by the late-stage functionalization of complex bioactive molecules.

Site-Selective Functionalization of Pyridinium Derivatives via Visible-Light-Driven Photocatalysis with Quinolinone.

The selective installation of phosphinoyl and carbamoyl moieties on the pyridine scaffold is an important transformation in synthetic and medicinal chemistry. By employing quinolinone as an efficient organic photocatalyst, we developed a catalytic system driven by visible light that forms phosphinoyl and carbamoyl radicals, which react with various heteroarenium derivatives under mild, transition-metal-free conditions. This straightforward and environmentally friendly synthetic method represents a new approach to site-divergent pyridine functionalization that offers considerable advantages in both simplicity and efficiency. Ambient temperature is sufficient for the formation of the reactive radicals, and the site-selectivity can be switched from C2 to C4 by changing the radical coupling sources. Under standard reaction conditions, phosphinoyl radicals give access to C4 products, while carbamoyl radicals selectively give C2 products. We found that the carbamoyl radical overcomes the intrinsic preference for forming the ortho-product by allowing the oxo functionality of the carbamoyl radical to electrostatically engage the nitrogen of the pyridinium substrate, which preferentially gives the ortho-product. The phosphinoyl radical cannot engage in the same interaction, because the phosphorus is too large. This novel synthetic route tolerates a broad range of substrates and provides a convenient and powerful synthetic tool for accessing the core structures of numerous privileged scaffolds.

Iodine-Promoted Radical Cyclization in Water: A Selective Reaction of 1,6-Enynes with Sulfonyl Hydrazides.

An iodine-promoted one-pot radical cyclization reaction of 1,6-enynes with sulfonyl hydrazides to provide five-membered and hexatomic ring sulfonylated products under the same conditions is established. This reaction proceeded smoothly in water and gave the corresponding products by using I2/TBHP instead of expensive and toxic catalysts with C-S and C-I bond formed in one step. This method also allowed easy access to significant functional sulfones for potential applications in medicinal and organic chemistry.

Silver-promoted cinnamamidyl radical-mediated oxidative cascade cyclization: highly regioselective synthesis of phosphorylated azaspiro[4.5]decenones.

A silver-promoted oxidative cascade cyclization with a phosphorylation/1,5-aryl migration/desulfonylation/dearomatization process is presented here, providing an efficient method to synthesize azaspiro[4.5]decenones with high regioselectivity. The cinnamamidyl radical, which has rarely been reported before, plays a key role in this reaction.

Copper-catalyzed difunctionalization of activated alkynes by radical oxidation-tandem cyclization/dearomatization to synthesize 3-trifluoromethyl spiro[4.5]trienones.

A copper-catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO2CF3 or Langlois' reagent) has been developed incorporating a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3-(trifluoromethyl)-spiro[4.5]trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon-carbon single bonds and one carbon-oxygen double bond.

Convenient and highly efficient routes to 2 H-chromene and 4-chromanone derivatives: iodine-promoted and p-toluenesulfonic acid catalyzed cascade cyclizations of propynols.

A convenient strategy is presented for the easy preparation of a series of 2 H-chromenes under mild conditions through iodocyclization of readily accessible propynols. In addition, various 4-chromanones can be synthesized through a p-toluenesulfonic acid catalyzed cascade cyclization with high efficiency (yields up to 99 %). Our developed reaction systems are proven to have good functional-group applicability and can be scaled up to gram quantities in satisfactory yields. These systems also provide a new synthetic strategy for two types of important flavonoid skeleton without using costly and toxic metal catalysts. Additionally, the resulting halides could be further exploited in subsequent palladium-catalyzed coupling reactions, so these compounds could act as potential intermediates for the construction of some valuable drug molecules.

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.

[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.

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.

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.

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.

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.

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.

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.

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.