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Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide. Except for all guidelines that have been approached in clinic, anlotinib and Aurora-A inhibitors also have been proved to be effective in HCC. However, Anlotinib which is a member of anti-angiogenesis therapy, has achieved great benefits in clinical trials, but its single-agent treatment limitations are also very obvious like drug resistance. Aurora-A inhibitors are in clinical trials but has limited benefit. Combination therapy is clearly superior to monotherapy under the situation. So we hope to explore whether the combination of the two drugs can enhance their strengths and avoid their weaknesses to obtain more clinical benefits. We confirmed that alisertib and anlotinib had an inhibitory effect on HCC cells in a time-dose relationship at first. In vitro, cytological experiments showed that the combination of the two drugs had a synergistic effect on inhibiting cell proliferation, invasion, and metastasis, and promoting cell apoptosis. We also uncovered the underlying molecular mechanism by which the combination of Aurora-A inhibitor alisertib and anlotinib inhibited HCC by inhibiting the activation of the NF-ĸB signaling pathway. In a word, we have demonstrated that anlotinib combined with Aurora-A inhibitor is effective, which also broadens the horizon for anlotinib before officially enter the clinical treatment of HCC in the future.

Thin solid polymer electrolytes (SPEs) with good processability, improved room-temperature ionic conductivity, and better interfacial compatibility are urgently needed to develop solid-state batteries without safety and leakage issues. In-built electrolyte polymerization has emerged as a novel and effective platform to obtain such electrolytes. However, existing in-built methods usually involve heat, UV, γ irradiation, and so forth to initiate the polymerization and often require the addition of solvents to avoid the concentrated active propagating species, which inevitably afford solvent residues that persist in the electrolyte matrix, leading to complex SPE preparation processes, safety hazards, and side reactions with the electrodes. Herein, a simple solvent-free preparation of the poly(mPEGAA)-based electrolyte film was achieved via the photo-controlled radical polymerization under visible light irradiation via an in-built manner, which resulted in 99% monomer conversion within 5 min to obtain the polymer electrolytes with a controlled molecular weight distribution. Thanks to the mild and green conditions, a thin, solvent-free, and cross-linked SPE electrolyte film was obtained efficiently yet in a well-regulated manner, which gave rise to good interfacial compatibility and an improved room-temperature ionic conductivity of 1.5 × 10-4 S cm-1 at 25 °C. As-prepared solid-state LiFePO4|Li batteries based on the in-built thin SPE exhibited a high discharge areal capacity of 1.7 mA h cm-2 (164.6 mA h g-1) at an ambient temperature. Furthermore, the system displayed lithium dendrite suppression behavior and good long-term charge-discharge cycling in the Li symmetric battery for over 270 h, representing enhanced stability and capacities compared with ex-built systems.

Background PSMD14 played a vital roles initiation and progression of hepatocellular carcinoma (HCC). However, PSMD14 and its-related genes for the immune prognostic implications of HCC patients have rarely been analyzed. Therefore, we aimed to explore gene signatures and immune prognostic values of PSMD14 and its-related genes in HCC. Method Analyzed the expression of PSMD14 in multiple databases, and clinicopathologic characteristics associated with PSMD14 overall survival using Wilcoxon signed-ranktest, logistic and Cox regression, Kaplan-Meier method. An immune prognostic signature (including RBM45, PSMD1, OLA1, CCT6A, LCAT and IVD) was constructed and validated using the co-expression and cox regression analyses in TCGA, ICGC and TIMER datasets. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Results Increased PSMD14 expression in HCC was significantly associated with poor prognosis and clinicopathologic characteristics (grade, histologic stage, surgical approach and T stage, all p-values < 0.05). A total of six PSMD14-related genes were detected, which markedly related to overall survival and immune infiltrating levels in HCC patients. Using cox regression analysis, the PSMD14 and its-related genes were found to be an independent prognostic factor for HCC survival. Calibration curves confirmed good consistency between clinical nomogram prediction and actual observation. Immune prognostic model suggests that patients in the high‐risk group shown significantly poorer survival than patients in the low‐risk group. Conclusion We screened potential immune prognostic genes and constructed and verified a novel PSMD14-based prognostic model of HCC, which provides new potential prognostic biomarkers and therapeutic targets and lays a theoretical foundation for immunotherapy of HCC.

A porous polymeric ligand (PPL) has been synthesized and complexed with copper to generate a heterogeneous catalyst (Cu@PPL) that has facilitated the efficient C-N coupling with various (hetero)aryl chlorides under mild conditions of visible-light irradiation at 80 °C (58 examples, up to 99% yields). This method could be applied to both aqueous ammonia and substituted amines, and is compatible to a variety of functional groups and heterocycles, as well as allows tandem C-N couplings with conjunctive dihalides. Furthermore, the heterogeneous characteristic of Cu@PPL has enabled a straightforward catalyst separation in multiple times of recycling with negligible catalytic efficiency loss by simple filtration, affording reaction mixtures containing less than 1 ppm of Cu residue.

Topology influences the properties and applications of polymers. Consequently, considerable efforts have been made to control topological structures. In this work, we have developed a photoorganocatalyzed divergent synthetic approach based on reversible-deactivation radical polymerization (RDRP) that enables the preparation of both linear and branched fluoropolymers of low dispersity (Ð), a tunable degree of branching and high chain-end fidelity by exposure to LED light irradiation under metal-free conditions. This method promotes the generation of complicated structures (e.g., necklace-like and mop-like fluoropolymers) via chain-extension photo-RDRP, and provides a novel and versatile platform to access fluoropolymer electrolytes with high Li-ion transference number and good ionic conductivity, which should create improved opportunities for advanced material engineering.

The synthesis and characterization of linear poly(ether 1,2-glycerol carbonate)s derivatized with pendant butyl, octyl, or stearyl tethers are reported. The polymers are obtained via the ring-opening copolymerization of butyl, octyl, or stearic glycidyl ethers with carbon dioxide using the [

Poly(vinyl ether)s (PVEs) are useful materials of different applications. In this work, we have developed a versatile and highly efficient initiation approach based on thienyl chloride derivatives ...

Aggregation-induced emission (AIE) compounds have emerged as an important type of material in a variety of high-tech applications. 1,1-Diphenylvinylsulfides represent a new class of AIE luminogens following the restriction of intramolecular motion (RIM) mechanism. However, synthetic approaches that allow efficient access to such molecules are rather limited owing to the steric hindrance in the multi-aryl substituted ethene skeleton. Herein, we report a new and metal-free C–S bond construction strategy to access 1,1-diphenylvinylsulfides via thioetherification of 1,1-diphenylethenes with thiols under mild conditions. Moreover, the isolated yields were found to be dramatically improved by streamlining the synthesis using a simple continuous-flow setup. With the combined advantages of the new C–H sulfenylation protocol and continuous-flow chemistry, various 1,1-diphenylvinylsulfides were generated in good yields in a less than 50 min residence time without the use of metal catalysts from all easily accessible materials, and a variety of derivatives were easily afforded via post-modifications.

Along with high power capability and energy density, long cycle life is regarded an essential performance requirement for energy storage devices. The rapid capacitance decline of conducting polymer-based electrodes remains a major technical challenge and precludes their practical applications in supercapacitors. In this work, a polyaniline (PANI) network is synthesized via interfacial Buchwald–Hartwig polymerization for the first time, facilitating the construction of covalently connected PANI networks by ligand-promoted C–N bond formation. Particularly, the interfacial synthesis and subsequent gas release from pre-anchored protecting groups allow bottom-up and efficient access to porous cross-linked PANI (PCL-PANI) films that are free-standing and solvent-resistant. Upon assembling into supercapacitors, the PCL-PANI material enables an unprecedent long-term charge–discharge cycling performance (>18 000 times) without clear capacitance loss for an additive-free pseudocapacitive system. In addition, this synthesis affords electrodes entirely consisting of conducting polymers, yielding highly reversible gravimetric capacitance at 435 F gelectrode−1 in a two-electrode system, and a high gravimetric energy of 12.5 W h kgelectrode−1 while delivering an outstanding power density of 16 000 W kgelectrode−1, which is 10-fold higher than those of conventional linear PANI composite supercapacitors. This synthetic approach represents a novel and versatile strategy to generate additive/binder-free and high-performance conducting thin-films for energy storage., A covalently cross-linked polyaniline network is synthesized via interfacial Buchwald-Hartwig polymerization/deprotection, enabling the generation of additive/binder-free and high-performance conducting thin-films for energy storage.

Hepatocellular carcinoma (HCC) is the 6th most prevalent cancer and the 4th leading cause of cancer-related death worldwide. Mechanisms explaining the carcinogenesis of HCC are not clear yet. In recent years, rapid development of N6-methyladenosine (m6A) modification provides a fresh approach to disclosing this mystery. As the most prevalent mRNA modification in eukaryotes, m6A modification is capable to post-transcriptionally affect RNA splicing, stability, and translation, thus participating in a variety of biological and pathological processes including cell proliferation, apoptosis, tumor invasion and metastasis. METTL3 has been recognized as a pivotal methyltransferase and essential to the performance of m6A modification. METTL3 can regulate RNA expression in a m6A-dependent manner and contribute to the carcinogenesis, tumor progression, and drug resistance of HCC. In the present review, we are going to make a clear summary of the known roles of METTL3 in HCC, and explicitly narrate the potential mechanisms for these roles.

A nanoporous all-solid-state MOF-laden polymer electrolyte that is simply mediated by an electronic effect shows remarkably high lithium electrodeposition stability of hundreds of charge-discharge cycles and over 1500 operating hours, while maintaining a very small voltage polarization. This result is a significant improvement relative to conventional PEO and, when used in an all-solid-state battery (ASSB), this electrolyte enabled enhanced cycle life. This new all-solid-state electrolyte shows a promising rational design for the emerging microporous polymeric materials as novel SPEs in ASSBs.

Reprogramming of metabolism is one of the hallmarks of cancer, among which glucose metabolism dysfunction is the most prominent feature. The glucose metabolism of tumor cells is significantly different from that of normal cells. Glucose metabolism reprogramming of hepatocellular carcinoma (HCC) has become an important research hotspot in the field of HCC, a variety of tumor metabolic interventions have been applied clinically. Moreover, various Non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding (lncRNAs) as well as circular RNAs (circRNAs), have recently been proved to play potential roles in glucose metabolism. This review summarizes the effects of ncRNAs on HCC that participate in glucose metabolism and discuss the related mechanisms to find potential and effective targeted treatments for HCC.

Aurora-A is a mitotic serine/threonine-protein kinase and an oncogene. In normal cells, Aurora-A appears from G2 phase and localizes at the centrosome, where it participates in centrosome replication, isolation and maturation. Aurora-A also maintains Golgi apparatus structure and spindle assembly. Aurora-A undergoes ubiquitination-mediated degradation after the cell division phase. Aurora-A is abnormally expressed in tumor cells and promotes cell proliferation by regulating mitotic substrates, such as PP1, PLK1, TPX2, and LAST2, and affects other molecules through a non-mitotic pathway to promote cell invasion and metastasis. Some molecules in tumor cells also indirectly act on Aurora-A to regulate tumor cells. Aurora-A also mediates resistance to chemotherapy and radiotherapy and is involved in tumor immunotherapy. Clinical trials of Aurora-A molecular inhibitors are currently underway, and clinical transformation is just around the corner.

Background Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid cancer and the main origin of cancer-related deaths worldwide. Current strategies to treat advanced NSCLC are based on a combined approach of targeted therapy and chemotherapy. But most patients will eventually get resistance to either chemotherapy or targeted therapy, leading to the poor prognosis. The mechanism of NSCLC drug resistance is inconclusive and is affected by multiple factors. Long non-coding RNAs (LncRNAs) are non-coding RNAs (ncRNAs) longer than 200 nucleotides. Recent studies show that lncRNAs are involved in many cellular physiological activities, including drug resistance of NSCLC. It is of great clinical significance to understand the specific mechanisms and the role of lncRNAs in it. Conclusions Herein, we focus on the functional roles and the underlying mechanisms of lncRNAs in acquired drug resistance of NSCLC. LncRNAs have potential values as novel prognostic biomarkers and even therapeutic targets in the clinical management of NSCLC.

The synthesis and physicochemical properties of a series of non-flammable, thermally stable alkyl ether containing piperidinium ionic liquid electrolytes, containing lithium bis(trifluoromethanesulfonyl)imide, are described along with the superior performance of a lithium-ion supercapacitor containing a piperidinium electrolyte compared to a standard carbonate-based electrolyte at 100 °C.

While the conventional living cationic polymerization (LCP) provided opportunities to synthesizing well-defined polymers with predetermined molecular weights, desirable chemical structures and narrow dispersity, it is still important to continuously innovate new synthetic methods to meet the increasing requirements in advanced material engineering. Consequently, a variety of novel initiation/controlling systems have be demonstrated recently, which have enabled LCP with spatiotemporal control, broadened scopes of monomers and terminals, more user-friendly operations and reaction conditions, as well as improved thermomechanical properties for obtained polymers. In this work, recent advances in LCP is summarized with emerging initiation/controlling systems, including chemical-initiated/controlled cationic reversible addition-fragmentation chain transfer (RAFT) polymerization, photoinitiated/controlled LCP, electrochemical-controlled LCP, thionyl/selenium halide-initiated LCP, organic acid-assisted LCP, and stereoselective LCP. It is hoped that this summary will provide useful knowledge to people in related fields and stimulate new ideas to promote the development and application of LCP in both academia and industry.

Self-labeled inhibitors (SLIs) are promising for creating links, ranging from cancer therapy and metastatic pathways to mechanistic elucidation. In this study, a new category of “two-in-one” fluorescent xanthone inhibitors was developed for the systematic evaluation of anticancer activity and the selective imaging of cytoplasm in vitro. These xanthone inhibitors presented high fluorescent brightness, working over a wide pH range enabled by a “switchable reaction” of the heterocyclic backbone. The strength and nature of fluorescence were probed via spectroscopic methods and density functional theory calculations on the molecular level, respectively. Along with the potent anticancer activity, which was demonstrated using MTT and clonogenic assays with high fluorescent brightness in the cytoplasm, SLI 3fd could be established as a modeled self-monitoring drug in cancer therapy.

Given the increased use of room temperature ionic liquid electrolytes in Li-ion batteries, due to their non-flammability and negligible volatility, this study evaluates the lithiation kinetics to understand and improve the rate performance of Li-ion batteries. Lithium titanate spinel is used as a model electrode and the electrolyte is composed of LiTFSI and TFSI-coordinated alkoxy-modified phosphonium ionic liquid. Based on the analysis of activation energies for each process, we report that the charge-transfer reaction at the electrode/electrolyte interface is the rate-limiting step for cell operation. This finding is further supported by the observation that a 50-fold decrease in charge-transfer resistance at higher temperatures leads to a significant performance improvement over that of a traditional organic electrolyte at room temperature. Charge-transfer resistance and electrolyte wetting on the electrode surface are critical processes for optimal battery performance, and such processes need to be included when designing new ionic liquids in order to exceed the power density obtained with the use of current carbonate-based electrolytes.

A facile synthesis of highly functionized indanone fused multicyclic pyrrolines using the heterocyclic ketene aminal and ninhydrin is described. Derivative alkoxyl or amine substituted analogues were also directly achieved upon adding alcohols or amines as corresponding starting materials. The reaction conditions are environment friendly and have a good tolerance towards a variety of heterocyclic ketene aminals. A library including three series of molecularly diverse indanone fused pyrrolines with potential bioactivities was demonstrated to be rapidly constructed with good to excellent yields.

Fabrication of lithium-ion batteries that operate from room temperature to elevated temperatures entails development and subsequent identification of electrolytes and electrodes. Room temperature ionic liquids (RTILs) can address the thermal stability issues, but their poor ionic conductivity at room temperature and compatibility with traditional graphite anodes limit their practical application. To address these challenges, we evaluated novel high energy density three-dimensional nano-silicon electrodes paired with 1-methyl-1-propylpiperidinium bis(trifluoromethanesulfonyl)imide (Pip) ionic liquid/propylene carbonate (PC)/LiTFSI electrolytes. We observed that addition of PC had no detrimental effects on the thermal stability and flammability of the reported electrolytes, while largely improving the transport properties at lower temperatures. Detailed investigation of the electrochemical properties of silicon half-cells as a function of PC content, temperature, and current rates reveal that capacity increases with PC content and temperature and decreases with increased current rates. For example, addition of 20% PC led to a drastic improvement in capacity as observed for the Si electrodes at 25 °C, with stability over 100 charge/discharge cycles. At 100 °C, the capacity further increases by 3-4 times to 0.52 mA h cm(-2) (2230 mA h g(-1)) with minimal loss during cycling.

With the ongoing global effort to reduce greenhouse gas emission and dependence on oil, electrical energy storage (EES) devices such as Li-ion batteries and supercapacitors have become ubiquitous. Today, EES devices are entering the broader energy use arena and playing key roles in energy storage, transfer, and delivery within, for example, electric vehicles, large-scale grid storage, and sensors located in harsh environmental conditions, where performance at temperatures greater than 25 °C are required. The safety and high temperature durability are as critical or more so than other essential characteristics (e.g., capacity, energy and power density) for safe power output and long lifespan. Consequently, significant efforts are underway to design, fabricate, and evaluate EES devices along with characterization of device performance limitations such as thermal runaway and aging. Energy storage under extreme conditions is limited by the material properties of electrolytes, electrodes, and their synergetic interactions, and thus significant opportunities exist for chemical advancements and technological improvements. In this review, we present a comprehensive analysis of different applications associated with high temperature use (40–200 °C), recent advances in the development of reformulated or novel materials (including ionic liquids, solid polymer electrolytes, ceramics, and Si, LiFePO4, and LiMn2O4 electrodes) with high thermal stability, and their demonstrative use in EES devices. Finally, we present a critical overview of the limitations of current high temperature systems and evaluate the future outlook of high temperature batteries with well-controlled safety, high energy/power density, and operation over a wide temperature range.

The synthesis and characterization of a degradable version of poly(acrylic acid), poly(glyceric acid carbonate), are reported. Specifically, atactic and isotactic poly(benzyl glycidate carbonate)s are obtained via the ring-opening copolymerization of rac-/(R)-benzyl glycidate with CO2 using a bifunctional rac-/(S,S)-cobalt salen catalyst in high carbonate linkage selectivity (>99%) and polymer/cyclic carbonate selectivity (∼90%). Atactic poly(benzyl glycidate carbonate) is an amorphous material with a T(g) (glass transition temperature) of 44 °C, while its isotactic counterpart synthesized from enantiopure epoxide and catalyst is semicrystalline with a T(m) (melting temperature) = 87 °C. Hydrogenolysis of the resultant polymers affords the poly(glyceric acid carbonate). Poly(glyceric acid carbonate) exhibits an improved cell cytotoxicity profile compared to poly(acrylic acid). Poly(glyceric acid carbonate)s also degrade remarkably fast (t(1/2) ≈ 2 weeks) compared to poly(acrylic acid). Cross-linked hydrogels prepared from poly(glyceric acid carbonate) and poly(ethylene glycol) diaziridine show significant degradation in pH 8.4 aqueous buffer solution compared to similarly prepared hydrogels from poly(acrylic acid) and poly(ethylene glycol) diaziridine.

A series of novel fused polyhalogeno-7a-hydroxy-[1,2-a]indol-5-one derivatives has been synthesized with good yields based on the Nenitzescu reaction of heterocyclic ketene aminals (HKAs) with halogenated quinones without catalyst in acetone under room temperature. The highly efficient, catalyst-free and one pot synthesis serves as a nice addition to group-assisted-purification (GAP) chemistry, and the pure products were obtained simply by washing the crude products with 95% ethanol.

The synthesis and characterization of linear poly(ether 1,2-glycerol carbonate)s derivatized with pendant butyl, octyl, or stearyl tethers are reported. The polymers are obtained via the ring-opening copolymerization of butyl, octyl, or stearic glycidyl ethers with carbon dioxide using the [rac-SalcyCoIIIDNP] catalyst bearing a quaternary ammonium salt. Synthesized polymers were characterized by 1H and 13C NMR spectroscopy, FT-IR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and rheometry. Polymers with controlled molecular weights in the range of 8970–31 900 g/mol were obtained with low polydispersities between 1.1 and 1.4. Thermal properties of the materials confirm amorphous structures of the polymers with butyl and octyl chains, with glass transition temperatures of −24 and −34 °C, respectively. The stearyl tether polymer exhibited a melting point of 55 °C. Additionally, the potential of poly(butyl ether 1,2-glycerol carbonate) as a thermally stable solid polymer elect...

A concise and efficient synthesis of pyrrolo[1,2-a]imidazoles and imidazo[1,2-a]-pyridines was developed by regioselective aza-ene additions and regioselective cyclic–condensation reactions of heterocyclic ketene aminals with ethyl 3-benzoylacrylate or methyl acetylacrylate derivatives under catalyst-free conditions. This method has some advantages including high regioselectivity, good yields and simple work-up procedures.

An efficient and convenient method was developed for the preparation of 2-benzenesulfonothiol-HKAs via a silver(I)-mediated direct sulfenylation of heterocyclic ketene aminals (HKAs). The method involves a variety of functionalized substrates, leading to α-arylthioyl HKAs in a mild, easy operation, and mild reaction conditions.

An efficient and straightforward synthesis of polycyclic 1,4-dihydropyridine derivatives has been developed by reacting heterocyclic ketene aminals (HKAs) with 1,3-cyclohexanedione derivatives and a number of substituted salicylaldehyde, respectively, via three-component cascade reactions in water. This strategy provides an efficient and environmentally friendly approach for easy access to various new fused polycyclic 1,4-dihydropyridine derivatives without the need of organic solvents in moderate to good yields.

A three-component strategy for the efficient and diastereoselective synthesis of unprecedented polycyclic pyrroles (4) bearing four consecutive quaternary stereocenters has been developed. The reaction was performed with three readily available starting materials: heterocyclic ketene aminals (HKAs) (1), acenaphthylene-1,2-dione (2), and ethyl trifluoroacetylacetate (3). In the one-step cascade reaction, two C–C bonds, two C–Hetero bonds, four consecutive quaternary stereocenters, and two heterocycles were constructed. The established protocol presented outstanding diastereoselectivity (up to 99:1) and provided a valuable route to access highly functionalized polycyclic pyrroles with conciseness, rapidness, and practicability. The reaction is particularly attractive due to the following advantages: atom economy, optimum convergence, high bond-forming efficiency, and operational simplicity.

A concise and efficient synthesis of novel bicyclic pyrroles has been achieved by PdCl2-catalyzed cyclic condensation of six-membered heterocyclic ketene aminals (HKAs) or seven-membered HKAs with ethyl 2,3-diiodoacrylate and diethyl 2,3-diiodofumarate in the presence of Cs2CO3, respectively. A series of novel bicyclic pyridones have also been obtained via five-membered HKAs with diethyl 2,3-diiodofumarate under the optimized conditions in moderate yields. These reactions are the first application of a transition metal to catalyze the building blocks HKAs to form the bicyclic pyrrole library via condensation reaction.

As a classical and well-established named reaction, the Nenitzescu reaction is of special value for the construction of biologically meaningful 5-hydroxyindole derivatives. However, to date, its sister, the anti-Nenitzescu reaction and the corresponding synthetic methodology for 3a-hydroxy-indol-6-one derivatives, has remained an unexplored area. We discovered herein an environmentally benign, mild, and catalyst-free reaction in ethanol for the site-selective construction of rarely fused [1,2-a]indolone derivatives (3) from quinones (1) and heterocyclic ketene aminals (HKAs) (2) via an unexpected anti-Nenitzescu strategy. This unconventional methodology suggests that it will be suitable for the site-selective synthesis of 3a-hydroxy-indol-6-one derivatives from a green perspective. On the other hand, the developed target compounds 3 have a promising future for the further synthesis of aromatic 6-hydroxyindoles or dehydroxylated indol-6-ones in situ. In order to systematically elucidate the mechanistic details and controlling factors of the two Nenitzescu reactions, density functional theory (DFT) calculations were also performed. According to the computational results, the origin of site-selectivity can be explained by the following reasons: all energy barriers for the anti-Nenitzescu reaction can be overcome at room temperature, yet the extremely high energy barrier of imine–enamine tautomerization for the Nenitzescu reaction indicates its failure under the same conditions. The reduced density gradient (RDG) analysis hinted that the greater thermodynamic stability of the Nenitzescu product 3h′ mainly depends on the release of the strong steric effect.