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A novel kind of S -alkynylthio sulfonate, which can be directly activated under visible-light irradiation, has been developed for the radical addition of multiple bond systems and radical coupling with diazonium salts under photocatalyst-free conditions. This strategy features a broad substrate scope, high regioselectivity, excellent tolerance of functional groups, and the late-stage modification of drugs. Experimental and theoretical mechanistic investigations gave reasonable insight into the photolysis of S -alkynylthio sulfonates and C-S bond formation.

The SARS-CoV-2 main protease (M pro ) plays a crucial role in virus amplification and is an ideal target for antiviral drugs. Currently, authentic M pro is prepared through two rounds of proteolytic cleavage. In this method, M pro carries a self-cleavage site at the N-terminus and a protease cleavage site followed by an affinity tag at the C-terminus. This article proposes a novel method for producing authentic M pro through single digestion. M pro was constructed by fusing a His tag containing TEV protease cleavage sites at the N-terminus. The expressed recombinant protein was digested by TEV protease, and the generated protein had a decreased molecular weight and significantly increased activity, which was consistent with that of authentic M pro generated by the previous method. These findings indicated that authentic M pro was successfully obtained. Moreover, the substrate specificity of M pro was investigated. M pro had a strong preference for Phe at position the P2, which suggested that the S2 subsite was an outstanding target for designing inhibitors. This article also provides a reference for the preparation of M pro for sudden coronavirus infection in the future., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation., (© 2024 John Wiley & Sons Australia, Ltd.)

Members of the Flaviviridae family, encompassing the Flavivirus and Hepacivirus genera, are implicated in a spectrum of severe human pathologies. These diseases span a diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and adverse fetal outcomes, such as congenital heart defects and increased mortality rates. Notably, infections by Flaviviridae viruses have been associated with substantial cardiovascular compromise, yet the exploration into the attendant cardiovascular sequelae and underlying mechanisms remains relatively underexplored. This review aims to explore the epidemiology of Flaviviridae virus infections and synthesize their cardiovascular morbidities. Leveraging current research trajectories and our investigative contributions, we aspire to construct a cogent theoretical framework elucidating the pathogenesis of Flaviviridae -induced cardiovascular injury and illuminate prospective therapeutic avenues.

Novel sulfur reagents N -vinylthio phthalimides ( N -VTPs) have been employed as modular reagents for vinylthiolation, enabling the construction of aggregation-induced emission (AIE)-active tetraaryldivinyl sulfides (TADVSs) and diarylvinyl sulfides (DAVSs). Notably, TADVSs with sulfur insertion to ethene stators are reported as AIE luminogens (AIEgens) for the first time, and the corresponding photophysical properties and aggregated confirmation have been detailed for the demonstration of the AIE effect. A water-soluble TADVS with a quinolinium salt was prepared for cell imaging.

The aim of this paper was to reveal the correlation between the expression of ELOVL fatty acid elongase 6 (ELOVL6) gene in lung adenocarcinoma (LUAD) and its clinical significance, immune cell infiltration level and prognosis. Expression profile data of ELOVL6 mRNA were collected from the cancer genome atlas database to analyze the differences in ELOVL6 mRNA expression in LUAD tissues and normal lung tissues, and to analyze the correlation between ELOVL6 and information on clinicopathological features. Based on TIMER database, TISDIB database and GEPIA2 database, the correlation between ELOVL6 expression and tumor immune cell infiltration in LUAD was analyzed. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses of ELOVL6-related co-expressed genes were performed to identify the involved signaling pathways and to construct their co-expressed gene protein interaction networks. Drugs affected by ELOVL6 expression were screened based on the Cell Miner database. These findings suggest that ELOVL6 plays an important role in the course of LUAD, and the expression level of this gene has a close relationship with clinicopathological characteristics and survival prognosis, and has the potential to become a prognostic marker and therapeutic target for LUAD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The main protease (M pro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a vital role in viral replication. To study the function of M pro and screen inhibitors targeting M pro , it is necessary to prepare high-purity and high-activity M pro . In this study, four types of SARS-CoV-2 M pro s containing different termini were prepared, and their activities were determined successfully. The results showed that the activity of wild-type (WT) M pro was the highest, and the additional residues at the N-terminus but not at the C-terminus had a major effect on the enzyme activity. To explain this, the alignment of structures of different forms of M pro was determined, and the additional residues at the N-terminus were found to interfere with the formation of the substrate binding pocket. This study confirms the importance of the natural N-terminus to the activity of M pro and suggests that WT-GPH 6 (M pro with eight additional residues at the C-terminus) can be used as a substitute for authentic M pro to screen inhibitors. In short, this study provides a reference for the expression and purification of new coronaviruses confronted in the future., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient-dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. Furthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV., (© 2023 Wiley Periodicals LLC.)

Background: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear., Objective: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro ., Results: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2., Conclusion: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Herein, inorganic base K 3 PO 4 promoted divergent synthesis of CF 3 -substituted allenes, cyclopentenes, alkynes, and fluorinated enynes via regioselective nucleophilic addition of carbon nucleophiles to 2-trifluoromethyl-1,3-enynes was developed. With the choice of different carbon nucleophiles, various fluorinated compounds could be obtained under K 3 PO 4 /DMF reaction system. When malononitriles were used as nucleophiles, CF 3 -substituted allenes, cyclopentenes, and alkynes could be obtained, respectively. By using 1,3-dicarbonyl compounds as nucleophiles, ring-monofluorinated 4 H -pyrans could be prepared, and 1,1-difluoro-1,3-enynes could be furnished with the participation of diethyl malonate. Moreover, these five kinds of fluorinated allenes, alkenes, and enynes are valuable building blocks.

Symmetrical diaryl sulfides and diaryl disulfides have been efficiently and selectively constructed via the homocoupling of sodium arenesulfinates. The selectivity of products relied on the different reaction systems: symmetrical diaryl sulfides were predominately obtained under the Pd(OAc) 2 catalysis, whereas symmetrical diaryl sulfides were exclusively yielded in the presence of the reductive Fe/HCl system.

Differentiation between similarly reactive sites in molecules represents an ongoing challenge of organic synthesis. Herein we described one kind of versatile reagents, N -thiohydroxy succinimide esters (NTSEs), serving as both acyl and acylthio surrogates for the diverse synthesis of ketones, thioesters, amides, and acyl disulfides by selective cleavage of similarly reactive C-S and N-S bonds.

Single-cell RNA sequencing (scRNA-seq) is increasingly used in studies on gastrointestinal cancers. This study investigated the prognostic value of epithelial cell-associated biomarkers in colorectal cancer (CRC) using scRNA-seq data. We downloaded and analysed scRNA-seq data from four CRC samples from the Gene Expression Omnibus (GEO), and we identified marker genes of malignant epithelial cells (MECs) using CRC transcriptome and clinical data downloaded from The Cancer Genome Atlas (TCGA) and GEO as training and validation cohorts, respectively. In the TCGA training cohort, weighted gene correlation network analysis, univariate Cox proportional hazard model (Cox) analysis, and least absolute shrinkage and selection operator regression analysis were performed on the marker genes of MEC subsets to identify a signature of nine prognostic MEC-related genes (MECRGs) and calculate a risk score based on the signature. CRC patients were divided into high- and low-risk groups according to the median risk score. We found that the MECRG risk score was significantly correlated with the clinical features and overall survival of CRC patients, and that CRC patients in the high-risk group showed a significantly shorter survival time. The univariate and multivariate Cox regression analyses showed that the MECRG risk score can serve as an independent prognostic factor for CRC patients. Gene set enrichment analysis revealed that the MECRG signature genes are involved in fatty acid metabolism, p53 signalling, and other pathways. To increase the clinical application value, we constructed a MECRG nomogram by combining the MECRG risk score with other independent prognostic factors. The validity of the nomogram is based on receiver operating characteristics and calibration curves. The MECRG signature and nomogram models were well validated in the GEO dataset. In conclusion, we established an epithelial cell marker gene-based risk assessment model based on scRNA-seq analysis of CRC samples for predicting the prognosis of CRC patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Kai-yu Shen et al.)

High power 1.5 µm band fiber lasers are of great importance for many practical applications. Generally, the technical targets including high average output power, narrow linewidth, temporally suppressed intensity dynamics, high spectral purity, single transverse mode lasing, and excellent robustness are the major concerns when constructing a high-performance laser source. Here, we demonstrate the highest output power of a wavelength tunable 1.5 µm band random fiber laser based on the active fiber gain mechanism to the best of our knowledge. A master oscillator power-amplifier (MOPA) configuration is employed to greatly boost the output power to 20 watt-level with a single transverse mode lasing and the same linewidth as the seed, benefiting from the spectral broadening free feature when employing the random fiber laser as the seed. This work not only enriches the progress of random fiber laser, but also provides an attractive alternative in realizing high performance lasing light source at 1.5 µm band.

Even though polyurethane (PU) has been widely applied, its superhydrophobicity is inadequate for certain applications. As such, the development of superhydrophobic polyurethane (SHPU) has recently attracted significant attention, with numerous motivating reports in recent years. However, a comprehensive review that summarizes these state-of-the-art developments remains lacking. Thus, this review aims to fill up this gap by reviewing the recent preparation methods for SHPU based on superhydrophobic theories and principles. Three main types of methods used in promoting the hydrophobicity of PU are emphasized in this review; (1) incorporation of silicide or fluoride to lower the surface energy, (2) creation of micro/nano-scale rough surfaces by electrospinning or grafting of nanoparticles, and (3) integrating the earlier two methods to develop a synergistic approach. Furthermore, this review also discussed the various applications of SHPU in oil spill treatment, protective coating, self-healing materials and sensors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

3,4-Bisthiolated pyrroles constitute key cores in pyrrole-based semiconductors, and their electronic properties could be improved by the bisthio groups via the S -effect. Herein, a convenient method for the synthesis of 3,4-bisthiolated pyrroles has been developed through the AlCl 3 -catalyzed thiolation/cyclization of homopropargylic azides, and cyclic voltammetry and DFT calculations indicated that the desired 3,4-bisthiolated pyrroles had higher HOMO orbital energies and lower band gaps than the parent unsubstituted 2,5-diphenylpyrrole.

A flexible strain sensor is of significant importance in wearable electronics since it can help monitor the physical signals from the human body. Among various strain sensors, the polyurethane (PU)-based ones have received widespread attention owing to their excellent toughness, large working range, and nice gas permeability. However, the hydrophobicity of these sensors is not good enough, which may affect their use life and sensitivity. In this work, a high-performance strain sensor composed of PU, reduced graphene oxide (rGO), polydopamine (PDA), and 1 H ,1 H ,2 H ,2 H -perfluorodecane-thiol (PFDT) was designed and prepared. The results revealed that this PU/rGO/PDA/PFDT device possessed good superhydrophobicity with a water contact angle of 153.3°, a wide working strain range of 590%, and an outstanding gauge factor as high as 221 simultaneously. Because of these above advantages, the sensor worked effectively in detecting both subtle and large human movements (such as joint motion, finger motion, and vocal cord vibration) even in a high humidity environment. This strain sensor with high sensitivity, wide working range, and suitable modulus may have great potential in the field of flexible and wearable electronics in the near future.

Zika virus (ZIKV) is a typical mosquito-borne flavivirus known to cause severe fetal microcephaly and adult Guillain-Barré syndrome. Currently, there are no specific drugs or licensed vaccines available for ZIKV infection, and further research is required to identify host cell proteins involved in the virus's life cycle. Viruses are known to use host cell membrane skeletal proteins, such as actin and spectrin, to complete cell entry, transportation, and release. Here, based on immunoprecipitation, the Axl and ZIKV envelope (E) protein were shown to interact with the cell membrane skeleton protein 4.1R. Furthermore, deletion of 4.1R significantly reduced virus titer and viral protein synthesis. Our study showed that 4.1R is an important host cell protein during ZIKV infection and may be involved in the process of viral entry into host cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pathological cardiac hypertrophy is commonly associated with an upregulation of fetal genes, fibrosis, cardiac dysfunction, and heart failure. Previous studies have demonstrated that gastrodin (GAS) exerts cardioprotective action in the treatment of cardiac hypertrophy. However, the mechanism by which GAS protects against cardiac hypertrophy is yet to be elucidated. A mouse model of myocardial hypertrophy was established using an angiotensin II (Ang II) induction. GAS (5 or 50 mg/kg/d) was orally administered every day starting 7 days prior to the Ang II infusion combined with sham-operated controls. Heart samples from each group were collected for RNA sequencing. Using bioinformatics analysis, the key differentially expressed genes (DEGs) that are involved in reversing cardiac function were identified. Through bioinformatics analysis, the key DEGs that are involved in GAS's inhibition of Ang II-induced abnormal gene expression within the heart were identified. This was further validated using quantitative real-time PCR and Western blotting in neonatal rat cardiomyocytes (NRCMs). Oral administration of GAS significantly suppressed the Ang II-induced increase in heart size and heart weight to body weight. Furthermore, pretreatment of the NRCMs with GAS led to a dose-dependent inhibition of Ang II-induced increases in Nppb mRNA expression. We identified 620 upregulated and 87 downregulated Ang II-induced DEGs II, among which the expression patterns of 58 and 146 genes were inverted by low-dose and high-dose GAS, respectively. These inverted DEGs were found to be mainly enriched in the biological processes of regulation of Ras protein signal transduction, heart contraction, covalent chromatin modification, glucose metabolism, and positive regulation of cell cycle. Among them, the insulin-like growth factor type 2 ( Igf2 ) gene, which was found to be highly reversed and downregulated by GAS, served as a core gene linking energy metabolism, immune regulation, and systemic development. Subsequent functional verification demonstrated that IGF2, and its receptor IGF2R, is one of the targets of GAS that helps protect against cardiac hypertrophy. Taken together, we have identified, for the first time, IGF2/IGF2R as a potential target influenced by GAS in the prevention of cardiac hypertrophy., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The pathophysiology of cardiac hypertrophy is complex and multifactorial. Both the store-operated Ca 2+ entry (SOCE) and excessive autophagy are the major causative factors for pathological cardiac hypertrophy. However, it is unclear whether these two causative factors are interdependent. In this study, we examined the functional role of SOCE and Orai1 in angiotensin II (Ang II)-induced autophagy and hypertrophy using in vitro neonatal rat cardiomyocytes (NRCMs) and in vivo mouse model, respectively. We show that YM-58483 or SKF-96365 mediated pharmacological inhibition of SOCE, or silencing of Orai1 with Orail-siRNA inhibited Ang II-induced cardiomyocyte autophagy both in vitro and in vivo . Also, the knockdown of Orai1 attenuated Ang II-induced pathological cardiac hypertrophy. Together, these data suggest that Ang II promotes excessive cardiomyocyte autophagy through SOCE/Orai1 which can be the prime contributing factors in cardiac hypertrophy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Gao, Xie, Li, Ma, Song, Luo, Huang, Yang, Zhang, Huang, Yang and Yao.)

Spectral similarity indices were used to select similar soil samples from a spectral library and improve the predictive accuracy of target samples. There are many similarity indices available, and precisely how to select the optimum index has become a critical question. Five similarity indices were evaluated: Spectral angle mapper (SAM), Euclidean distance (ED), Mahalanobis distance (MD), SAM_pca and ED_pca in the space of principal components applied to a global soil spectral library. The accordance between spectral and compositional similarity was used to select the optimum index. Then the optimum index was evaluated if it can maintain the greatest predictive accuracy when selecting similar samples from a spectral library for the prediction of a target sample using a partial least squares regression (PLSR) model. The evaluated physiochemical properties were: soil organic carbon, pH, cation exchange capacity (CEC), clay, silt, and sand content. SAM and SAM_pca selected samples were closer in composition compared to the target samples. Based on similar samples selected using these two indices, PLSR models achieved the highest predictive accuracy for all soil properties, save for CEC. This validates the hypothesis that the accordance information between spectral and compositional similarity can help select the appropriate similarity index when selecting similar samples from a spectral library for prediction., Competing Interests: The authors have declared that no competing interests exist.

An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mechanisms were hereby explored. Results showed that five compounds (7s, 7t, 7v, 7w, 7γ) could induce endothelium-independent relaxation in high extracellular K + - and phenylephrine-precontracted C57 mice aortic rings. These five compounds, unlike other commonly used vasodilators, could slowly but effectively inhibit vasoconstriction., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Thiolation/cyclization of homopropargylic tosylamides allowed the selective synthesis of 3-thiolated pyrroles and pyrrolines controlled by solvents. Moreover, the desired 3-thiolated pyrroles were readily transformed to organic fluorophores benzothienopyrrole and bisthiolated boron dipyrromethene (S-BODIPY).

The Rh(I)-catalyzed cascade formation of carbenoid followed by a carbonylative cyclization of silyl diynes has been established to achieve diverse ortho silyl-substituted phenolics, enabling access to fully substituted aryne precursors via a one-step fluorosulfurylation. The silyl mask on the termini of alkynes is demonstrated not only to suppress the undesired oxidation but also to control the selectivity of CO insertion. Straightforward access to fully substituted arynes was comprehensively established and applied for the efficient construction of polycyclic aromatic molecules.

Background: Hepatocellular carcinoma (HCC) with tumor thrombus in the bile duct (BDTT) is easily misdiagnosed or mistreated due to the clinicopathological diversity of the thrombus and its relationship with primary lesions., Aim: To propose a new classification for HCC with BDTT in order to guide its diagnosis and treatment., Methods: A retrospective review of the diagnosis and treatment experience regarding seven typical HCC patients with BDTT between January 2010 and December 2019 was conducted., Results: BDTT was preoperatively confirmed by computed tomography/magnetic resonance imaging in only four patients. Three patients with recurrent HCC and one patient with first-occurring HCC had no visible intrahepatic tumors; of these, misdiagnosis occurred in two patients, and three patients died. One patient was mistreated as having common bile duct stones, and another patient with a history of multiple recurrent HCC was misdiagnosed until obvious biliary dilation could be detected. Only one patient who received hepatectomy accompanied by BDTT extraction exhibited disease-free survival during the follow-up period. A new classification was proposed for HCC with BDTT as follows: HCC with microscopic BDTT (Type I); resectable primary or recurrent HCC mass in the liver with BDTT (Type II); BDTT without an obvious HCC mass in the liver (Type III) and BDTT accompanied with unresectable intra- or extrahepatic HCC lesions (Type IV)., Conclusion: We herein propose a new classification system for HCC with BDTT to reflect its pathological characteristics and emphasize the significance of primary tumor resectability in its treatment., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second-most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris water maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Aβ1-42 in BCCAO rats by enzyme-linked immunosorbent assay. Post-translational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlights the importance of PTMs in neurodegenerative diseases. In this study, we used western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl-PTMs., (© 2020 John Wiley & Sons Australia, Ltd.)

A novel P(NMe 2 ) 3 -mediated tandem (1 + 4) annulation between aroylformates and δ-tosylamino enones has been developed that affords a facile synthesis of functionalized pyrrolidines in moderate to excellent yields with exclusive chemoselectivity and high diastereoselectivity. Mechanistic investigation reveals that the reaction proceeds through an unprecedented P(NMe 2 ) 3 -mediated reductive amination/base-catalyzed Michael addition cascade. The reaction herein also represents the first study of the reactivity patterns of the Kukhtin-Ramirez adducts toward ambiphilic nucleophile-electrophiles.

Primitive neuroectodermal tumours (PNETs) are rare malignant small round cell tumours. Notably, despite widespread reports of PNET in multiple parts of the body, it is extremely rare in the pelvis. Here, a rare case of giant PNET of the pelvis, that was treated with surgical intervention comprising hemipelvectomy and amputation, is reported. A 42-year-old female patient presented with an enlarged mass on the left hip and severe pain in the left lower extremity for the previous 6 months. Preoperative imaging examinations indicated an irregular soft tissue-like signal shadow sized 19 × 15 × 12 cm at the left ilium and sacrum. After surgical intervention involving left hemipelvectomy and amputation, the tumour was diagnosed by pathology as PNET. During the courses of postoperative radiotherapy and chemotherapy, local recurrence and distant metastasis occurred, and the patient died 9 months following surgical treatment. To the best of the authors' knowledge, the current case is the largest pelvic PNET resection reported to date. Pelvic PNET is extremely malignant and has a high mortality rate regardless of surgical treatment, however, surgical resection of the lesion may relieve the symptoms, extend life, and improve quality of life to a certain extent.

Disulfide bonds are a significant motif in life and drug-delivery systems. In particular, steric hindrance and stereoscopic disulfide linkers are closely associated with the stability of antibody-drug conjugates, which affects the potency, selectivity, and pharmacokinetics of drugs. However, limited availability and diversity of tertiary thiols impede the construction of steric and stereoscopic disulfides for cross-linkage in biochemistry and pharmaceuticals. Through modulating the mask effect of disulfurating reagents, we develop a facile and robust strategy for construction of diverse steric and stereoscopic disulfides via N -dithiophthalimides. The practical cross-linkage of biomolecules including amino acids, saccharides, and nucleosides with different drugs and fluorescent molecules is successfully established through hindered disulfide linkers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A facile method for the synthesis of 4-chalcogenylated pyrazoles has been developed via electrophilic chalcogenation/cyclization of α,β-alkynic hydrazones. The cyclization of α,β-alkynic aldehyde hydrazones could be induced by using either sulfenyl chloride or the S-electrophiles generated in situ from the reaction of NCS and arythiol. The developed method was successfully applied to the synthesis of the sulfenyl analogue of celecoxib.

Background: This present study is aimed to retrospectively assess the efficacy of three-dimensional (3D) printing assisted osteotomy guide plate in accurate osteotomy of adolescent cubitus varus deformity., Material and Methods: Twenty-five patients (15 males and 10 females) with the cubitus varus deformity from June 2014 to December 2017 were included in this study and were enrolled into the conventional group (n = 11) and 3D printing group (n = 14) according to the different surgical approaches. The operation time, intraoperative blood loss, osteotomy degrees, osteotomy end union time, and postoperative complications between the two groups were observed and recorded., Results: Compared with the conventional group, the 3D printing group has the advantages of shorter operation time, less intraoperative blood loss, higher rate of excellent correction, and higher rate of the parents' excellent satisfaction with appearance after deformity correction (P < 0.001, P < 0.001, P = 0.019, P = 0.023). Nevertheless, no significant difference was presented in postoperative carrying angle of the deformed side and total complication rate between the two groups (P = 0.626, P = 0.371)., Conclusions: The operation assisted by 3D printing osteotomy guide plate to correct the adolescent cubitus varus deformity is feasible and effective, which might be an optional approach to promote the accurate osteotomy and optimize the efficacy.

The anterior transpedicular screws (ATPS) fixation is a valuable discovery in the field of lower cervical spine (LCS) reconstruction, as it has the advantages of both anterior and posterior approaches. In recent years, with in-depth research on ATPS fixation related to anatomy, biomechanical tests, and clinical applications, its firm stability and excellent biomechanical properties have been recognized by more and more surgeons. Although ATPS fixation has been gradually applied in clinic settings under the promotion of emerging distinctive instruments, its long-term efficacy still needs to be further clarified due to the lack of large sample size studies and long-term follow-up. Nevertheless, it is believed that with the maturity of digital devices and the development of precision medicine, ATPS fixation has a promising prospect.

A new kind of electrophilic alkynylthiolating reagent, called N -alkynylthio phthalimide, is designed and synthesized herein. This electrophilic sulfenylating reagent can be easily prepared in three steps from commercially available phthalimide and corresponding silver acetylide. Furthermore, the N -alkynylthio phthalimides are demonstrated to be efficient alkynylthio transfer reagents that can react with various C-nucleophiles, including β-ketoesters, aryl boronic acids, and Grignard reagents to afford a diverse range of alkynyl thioethers under mild conditions.

Herein, we report an efficient nickel-catalyzed direct cyclization of amines with alcohols for the synthesis of various nitrogen containing heterocycles. These processes employ the sustainable "borrowing hydrogen" strategy and have many advantages, such as earth-abundant metal catalysts, easily available starting materials, wide synthetic versatility and harmless waste emission.

Objective: The aim of this study was to investigate long non-coding RNA (lncRNA) TP73-AS1 expression in hepatocellular carcinoma (HCC) tissues and cells, and to further investigate whether it can accelerate the progression of HCC by regulating microRNA-103., Patients and Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine TP73-AS1 expression in 60 pairs of HCC tissues and adjacent ones, and the association between lncRNATP73-AS1 level and clinical indicators of HCC as well as patients' prognosis was analyzed. Meanwhile, qRT-PCR was used to further verify TP73-AS1 expression in HCC cell lines. The lncRNA TP73-AS1 knockdown model was constructed using lentivirus in the HCC cell lines, including Bel-7402 and HepG2. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays were performed to figure out the influence of TP73-AS1 on the basic biological function of the HCC cells. Finally, the involved potential regulatory mechanism was explored using cell recovery experiments, and the relationship between TP73-AS1 and microRNA-103 was further studied., Results: QRT-PCR results indicated that TP73-AS1 expression in HCC samples was conspicuously enhanced compared with paracancerous tissues, and patients with a relatively high level of TP73-AS1 had a higher tumor stage and a lower overall survival rate. Meanwhile, the proliferation ability of cells in the sh-TP73-AS1 group was strikingly lower than that in the control group, while cell apoptosis showed the opposite trend. Besides, qRT-PCR results indicated a negative correlation between microRNA-103 and TP73-AS1 in HCC tissue specimens. The results of the luciferase reporting assay revealed that TP73-AS1 could be targeted by microRNA-103 through binding site. In addition, the cell recovery experiment demonstrated that TP73-AS1 and microRNA-103 might have a mutual regulation, and the two of which could together affect the malignant progression of HCC., Conclusions: TP73-AS1 expression was conspicuously enhanced both in HCC tissues and cell lines, which were associated with advanced tumor stage and poor prognosis. In addition, TP73-AS1 could accelerate the proliferation of HCC cells by regulating microRNA-103.

An efficient method for the synthesis of 4-sulfenyl isoxazoles has been developed via AlCl 3 -mediated electrophilic cyclization/sulfenylation of 2-alkyn-1-one O-methyloximes. Remarkably, N-arylsulfanylsuccinimides are employed as electrophiles for the construction of 4-arylsulfanyl isoxazoles, and 4-alkylsulfanyl isoxazoles are accessed with dialkyl disulfides as electrophiles.

The asymmetric aza-Henry reaction of N-Boc imines and nitroalkanes was realized in the presence of 10 mol % dinuclear zinc-AzePhenol catalysts under ambient conditions. A variety of nitroamines were obtained in good yields (up to 97%) with excellent enantioselectivities (up to 99% ee) and high diasteroselectivity (up to 14:1 dr). Our protocol combined the operational simplicity and mild reaction conditions, thus making the process amenable for technical applications.

Coronary artery disease (CAD) is quite a common disease with high risk. It was reported that microRNAs (miRNAs) had significant effect on the occurrence of CAD. The previously published results are inconsistent due to the parameters, such as sequencing platform, samples selection, and the filter conditions. Here we aimed to explore the critical miRNAs in the occurrence of CAD, which may function as the potential biomarkers. A total of 12 representative datasets of miRNAs related to the occurrence of miRNAs were finally selected, and the critical miRNAs were determined by the comparison of the overlap relations. TargetScan software was used to predict the target genes of these critical miRNAs. Besides, DAVID and Tfacts dataset were used to analyze the functional enrichment and the transcriptional factors analysis. At last, a total of six signature miRNAs were identified, among which five were significantly upregulated and one was downregulated. The target gene of upregulated miRNAs was mostly enriched in the process of RNA Polymerase II promoter and the transcription of DNA template, whereas the target genes of downregulated miRNAs were mostly enriched in the regulation of transcription, DNA-templated. Besides, the result of the transcriptional factor analysis showed that there were 43 factors coexisting in two kinds of target genes. In summary, six critical miRNAs, as well as the corresponding target genes and transcriptional factors, were identified in the occurrence of CAD by bioinformatics analysis. These identified miRNAs may function as potential biomarkers in the clinical management of CAD., (© 2018 Wiley Periodicals, Inc.)

A new and convenient method for one-pot synthesis of α-arylhydrazo-β-keto sulfones is developed via Cu (II)-catalyzed oxysulfonylation/diazenylation of alkenes. This four-component cascade reaction enables a series of α-arylhydrazo-β-keto sulfone derivatives accessed from readily available alkenes, sulfinates, and diazonium salts under aerobic conditions. Furthermore, the 3-sulfonyl cinnolin-4(1 H)-one skeleton is successfully constructed from the corresponding α-arylhydrazo-β-keto sulfone product under basic conditions.

Herein, we report a chemoselective P(NMe 2 ) 3 -mediated reductive epoxidation of α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones with aldehydes and ketones, leading to an efficient synthesis of a wide range of highly functionalized unsymmetrical epoxides in moderate to excellent yields and diastereoselectivities. The Kukhtin-Ramirez adduct, which is exclusively generated in situ from an α-dicarbonyl compound and P(NMe 2 ) 3 , plays a key role in governing the chemoselectivity. It represents the first practical synthesis of unsymmetrical epoxides via direct reductive epoxidation of two different carbonyl electrophiles and also complements the existing methods of generating epoxides.

Objectives: To investigate the efficiency of a new cascade biocatalysis system for the conversion of R, S-β-amino alcohols to enantiopure vicinal diol and β-amino alcohol., Results: An efficient cascade biocatalysis was achieved by combination of a transaminase, a carbonyl reductase and a cofactor regeneration system. An ee value of > 99% for 2-amino-2-phenylethanol and 1-phenyl-1, 2-ethanediol were simultaneously obtained with 50% conversion from R, S-2-amino-2-phenylethanol. The generality of the cascade biocatalysis was further demonstrated with the whole-cell approaches to convert 10-60 mM R, S-β-amino alcohol to (R)- and (S)-diol and (R)- and (S)-β-amino alcohol in 90-99% ee with 50-52% conversion. Preparative biotransformation was demonstrated at a 50 ml scale with mixed recombinant cells to give both (R)- and (S)-2-amino-2-phenylethanol and (R)- and (S)-1-phenyl-1, 2-ethanediol in > 99% ee and 40-42% isolated yield from racemic 2-amino-2-phenylethanol., Conclusions: This cascade biocatalysis system provides a new practical method for the simultaneous synthesis of optically pure vicinal diol and an β-amino alcohol.

Switchable ortho/ipso-cyclization of N-arylpropynamides induced with N-sulfanylsuccinimides as general sulfur reagents is reported. In the presence of MeOH, para-fluoro N-arylpropynamides exclusively undergo the ipso-cyclization to give 3-sulfenyl azaspiro[4,5]trienones. Two kinds of bioactive heterocycles, benzothieno-[3,2-b]quinoline and -[2,3-c]quinolone, have been directly and efficiently prepared from the corresponding sulfenylated products.

Objective: To define the survival effect of surgery of primary adrenal malignant lesions in metastatic adrenocortical carcinoma (ACC) patients., Patients and Methods: We used the Surveillance, Epidemiology and End Results (SEER) database (1973-2014) to identify metastatic ACC patients (stage IV by using European Network for the Study of Adrenal Tumors stage classification). Correlated variables, including age, sex, race, tumor laterality, treatment modality, lymph node dissection, surgery of metastatic site, tumor size, and tumor stage, were extracted. Univariate and multivariate Cox regression analyses were used to define the efficacy of surgery on survival outcomes, including overall survival and cancer-specific survival of ACC., Results: There were 290 metastatic ACC patients identified from the database. The overall median survival time was 7 (95% CI, 6-8) months. Among these patients, 118 patients received primary site surgery and 172 patients did not. In both univariate and multivariate analyses, primary site surgery significantly improved both overall (hazard ratio 0.413, 95% CI, 0.299-0.571, P <0.01) and cancer-specific survival (hazard ratio 0.408, 95% CI, 0.290-0.574, P <0.01) for metastatic ACC patients., Conclusion: Our study suggests that primary site surgery in metastatic ACC patients significantly improved overall and cancer-specific survival. Further multicenter prospective studies are still needed to validate these outcomes., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To define the prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) for adrenocortical carcinoma (ACC). Patients and Methods: We used the Surveillance, Epidemiology and End Results (SEER) database (1973-2014) to identify ACC patients. Correlated variables, including age, sex, race, tumor laterality, marital status at diagnosis, treatment of primary site, lymph node dissection, radiation therapy, chemotherapy, tumor size and tumor stage, were extracted. Univariate and multivariate Cox regression were used to define the prognostic factors. Harrell’s concordance index (C index) was calculated to evaluate the discrimination ability for the prognostic predictive models. Results: There were 749 ACC patients identified from the database. The overall median survival time was 22 (95%CI, 18-25) months. In multivariate analysis, age, treatment, chemotherapy and tumor stage were independent risk factors for both overall and cancer-specific survival. Tumor stage had a dominant effect on the cancer prognosis. Additionally, the ENSAT stage had better discrimination than the AJCC stage group in different predictive models. Conclusion: Our study shows that age, treatment of primary site, chemotherapy and tumor stage were prognostic factors for overall and cancer-specific mortality in ACC patients. Among these factors, tumor stage had a dominant effect. The ENSAT stage was more discriminative than the 7th AJCC stage group. Further multi-center prospective validation is still needed to confirm these outcomes., (Creative Commons Attribution License)