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Acquired resistance remains a major barrier for the treatment of non-small cell lung cancer, while cancer stem cells (CSCs) usually lead to the occurrence of drug resistance. We herein report a series of platinum(IV) prodrugs containing CSCs-inhibitory species derived from a known CSCs inhibitor BBI608 in the axial position. Among them, complex

Increasing evidence indicates that the cancer stem cell (CSC) subpopulation contributes to the therapeutic resistance and metastasis of tumors, leading to patient recurrence and death. Herein, we designed and synthesized several compounds by conjugating lapatinib derivatives with different CSC inhibitors to treat with lapatinib-induced MDA-MB-231 drug-resistant cells. In vitro biological studies indicated that 3a showed strong cytotoxicity and EGFR enzyme inhibitory activity and effectively reversed lapatinib-mediated resistance of MDA-MB-231 cells via inhibiting triple-negative breast cancer (TNBC) cell stemness and the AKT/ERK signaling pathway. In addition, 3a was capable of strongly suppressing the invasion and migration of TNBC cells by inhibiting the Wnt/β-catenin signaling pathway and MMP-2 and MMP-9 protein expression. In vivo tumorigenicity tests showed that 3a could inhibit the occurrence of TNBC by inhibiting BCSCs, proving 3a is a potential EGFR and CSC dual inhibitor for TNBC treatment.

Multifunctional entities have recently been attractive for the development of anticancer chemotherapeutic drugs. However, such entities with concurrent CK2 along with cancer stem cell (CSC) inhibitory activities are rare in a single small molecule. Herein, a series of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine derivatives were synthesized using a known CK2 inhibitor, silmitasertib (CX-4945), as the lead compound. Among the resulting compounds, 1c exhibited stronger CK2 inhibitory activity with higher Clk2/CK2 selectivity than CX-4945. Significantly, 1c could modulate the Akt1(ser129)-GSK-3β(ser9)-Wnt/β-catenin signaling pathway and inhibit the expression of the stemness marker ALDH1A1, CSC surface antigens, and stem genes, showing potent CSC inhibitory activity. Moreover, 1c also displayed superior pharmacokinetics and antitumor activity compared with CX-4945 sodium salt, without obvious toxicity. The favorable antiproliferative and antitumor activity of 1c, its high inhibitory selectivity for CK2, and its potent inhibition of cancer cell stemness make this molecule a candidate for the treatment of cancer.

Robotic Manipulators (RM) are nonlinear and coupling system with time-variant and model uncertainties. In addition, RM are subject to different types of disturbances in practice, such as joint frictions, unknown payloads, and interferences from external systems. In this paper, these adverse factors are regarded as disturbance, and classifies them into internal disturbances and external disturbances. In order to achieve high-precision control, a Nonlinear Disturbance Observer (NDO) is designed to suppress external disturbances, and a Fuzzy Logic System (FLS) is designed to compensate internal disturbances. The scheme can effectively suppress the disturbance and improve the control accuracy. The validity of the scheme is shown by computer simulations of a two-link robot manipulator.

The visible light photocatalytic activity and stability of bare Zn3Nb2O8 and carbon doped Zn3Nb2O8 (C–Zn3Nb2O8) were enhanced with nitrogen and carbon co-doped Zn3Nb2O8 (N/C–Zn3Nb2O8) for the oxidative and reductive degradation of pH-sensitive substrates, such as Cr(VI), Cu(II), methyl orange, and tetracycline hydrochloride. Compared to pure Zn3Nb2O8, the band structure of N/C–Zn3Nb2O8 was optimized with the conduction band at −0.37 eV and the valence band at 1.61 eV due to the co-doping of nitrogen and carbon, which could stimulate the formation of ˙OH and ˙O2− radicals. Moreover, the N/C–Zn3Nb2O8 catalyst was highly improved by the synergistic effect of carbon and nitrogen dopants on the visible light absorption, the charge conductivity, and the electron–hole pair separation. In addition, the N/C–Zn3Nb2O8 catalyst with a negatively charged surface and layered structure can selectively adsorb and degrade some pH-sensitive pollutants, thus achieving high photocatalytic activity in visible light irradiation and stable recyclability by designing a regeneration test and controlling the pH range.

As one of the key features of tumor, inflammation attracts much attention of many researchers for antitumor study, in which non-steroidal anti-inflammatory drugs (NSAIDs) have been widely investigated in anti-inflammatory treatments in cancers. Herein, we report a series of novel platinum(II) complexes derived from conjugation of several NSAIDs derivatives with two antitumor platinum(II) agents. The antitumor inhibitory effects of the synthesized compounds on a number of cancer cell lines were estimated. By taking the advantage of two bioactive moieties, these compounds exhibited stronger antitumor activity than their parent platinum agents, and some appeared to have capability of overcoming cisplatin resistance. Among them, IA-1 showed the best cytotoxicity and even exhibited stronger antitumor activity than cisplatin. Further research indicated that IA-1 induced significant DNA damage and ROS generation, accompanied by high cellular platinum accumulation, resulting in a much higher apoptosis rate than cisplatin in A2780 cells. Moreover, IA-1 was found to inhibit metastasis and invasion of A2780 cells by suppressing the COX-2/JAK2/STAT3 axis. All these results revealed that introduction of NSAIDs species efficiently sensitized cancer cells to the synthetic compounds, proving that NSAIDs can enhance the activity of the platinum(II) agents via inhibiting inflammation in cancer cells.

Focused on the removal of the complicated residual antibiotic in aqueous environment, in this work, a novel carbon dots (C-dots) sensitized 2D-2D heterojunction of BiVO4/Bi3TaO7 were assembled through a simple hydrothermal process. The characteristic by TEM, SEM, and XPS confirmed C-dots evenly anchored on the surface of BiVO4/Bi3TaO7 heterojunction. The as-prepared C-dots/BiVO4/Bi3TaO7 showed superior performance for the degradation of the various antibiotics under visible light illumination. When the concentration of C-dots in the composite is 3 wt.%, the photodegraded rates are obtained to be 91.7%, 89.3%, 87.1%, for tetracycline (TC), amoxicillin (AMX) and ciprofloxacin (CIP), respectively, without significant deactivation during consecutive ten recycle experiments. Furthermore, by assessing the antibiotics mixture solution of TC, AMX and CIP, it is proposed that the prepared samples are potentially effective for the wastewater effluents. A probable mechanism was reasonably proposed. The improved photocatalytic activities could be attributed to the unique construction of the C-dots mediated heterojunction, which could expedite electron migration, improve light harvesting capacity and enhance charge separation efficiency. The present investigation may provide a new perspective to design C-dots mediated heterojunction which could be a potential visible-light-driven photocatalysts for the better practical applications in remediation of broad-spectrum antibiotic residues.

Cancer stem cells (CSCs) have a pivotal impact in drug resistance, tumor metastasis, and progression of various cancer entities, including in non-small cell lung cancer (NSCLC). A CK2 inhibitor HY1 was found to show potent CSC inhibitory effects in A549 cells. By taking advantage of inherent CK2 specificity and CSC inhibition of HY1, a Pt(II) agent (HY1-Pt) was developed by conjugation of HY1 with an active Pt(II) unit to reverse cisplatin-induced resistance in A549/cDDP cell treatment. In vitro biological studies indicated that HY1-Pt can target CK2, suppress DNA damage repair, reinforce cellular accumulation of platinum, and reverse resistance apart from effectively inhibiting CSCs through Wnt/β-catenin signal pathway in A549/cDDP cells. Significantly, HY1-Pt presented an acceptable pharmacokinetic behavior and exhibited higher tumor growth inhibitory efficacy than cisplatin either in A549 or A549/cDDP xenograft models with low toxicity. Overall, HY1-Pt is a promising drug candidate for NSCLC treatment.

Cisplatin, a representative of platinum-based drug, is clinically and widely used in the treatment of various types of malignant cancer. However, its non-selectivity to almost all the cell lines and resistance in long-term use severely limit its scope of use. As biotin-specific uptake systems are overexpressed in many types of tumors but rarely occur in normal tissues, making biotin a promising target for cancer treatment. In the study, we synthesized the Pt(II) complex C2 and determined its biological activities. The existence of biotin enhanced the ability of the complex to target tumors, while the introduction of a naphthalimide compound makes it possible to diagnose tumors and monitor their progress. We have also introduced a known Pt(II) complex DN604, which not only retains the excellent cytotoxicity of platinum drugs, but also inhibits the expression of DNA double-strand breaks (DSBs) repair-related NHEJ protein Ku70 and HR protein Rad51. In summary, we report a novel trifunctional Pt(II) complex that could target tumor cells, monitor tumor progression, and reverse DSBs repair-induced cisplatin-resistance.

Focused on the removal of the complicated residual antibiotic in aqueous environment, in this work, a novel carbon dots (C-dots) sensitized 2D-2D heterojunction of BiVO

In this work, potassium tantalates (KxTaxO3x, x = 1 or 2) with different crystal structures and morphologies are synthesized with a one-step hydrothermal method. The concentration of the KOH reactant played a crucial role in controlling the morphology of KxTaxO3x. When the concentration of KOH is low, an octahedral pyrochlore (K2Ta2O6) is obtained. In contrast, the cubic perovskite (KTaO3) is obtained at high KOH concentrations. Pd nanoparticles loaded onto K2Ta2O6 and KTaO3 (Pd/K2Ta2O6, Pd/KTaO3) electrocatalysts are then prepared with reflux reduction in ethanol. X-ray photoelectron spectroscopy results imply that the loading palladium is in the main Pd° form. The electrocatalytic activity of the Pd/K2Ta2O6 and Pd/KTaO3 electrocatalysts is investigated using cyclic voltammetry (CV) toward ethylene glycol (EG) oxidation in an alkaline medium. The CV results show that Pd/K2Ta2O6 and Pd/KTaO3 electrocatalysts modified glassy carbon electrodes have excellent catalytic activity for EG electrooxidation in an alkaline medium, superior to that of commercial Pd/C (10%). The enhancement of their electrocatalytic activity was owing to the synergistic reaction between Pd and KxTaxO3x. In addition, the electronic structure of the Pd/K2Ta2O6 and Pd/KTaO3 electrocatalysts was assessed using density functional theory. The calculation results indicated that electron transfer occurred in the complex region of Pd and KxTaxO3x.

Focused on the decontamination of pharmaceutical pollutants via an adsorption approach, the adsorptive mode and capacity of adsorbents have been explored with a strategy by incorporating Ti into graphene (TG) frame using the density functional theory (DFT). Aspirin is used as a model molecule and pristine graphene (PG) as comparative substrate in this study. It is notified for PG, aspirin is adsorbed with a C-ring parallel orientation. It presents a weak physical adsorption through π-π interaction with an energy value of −0.846 eV. Whereas, a stronger chemical adsorption of aspirin on surface of TG with even lager adsorption energy of −2.772 eV is confirmed. The analysis based on Hirshfeld population and electronic distribution show the electrons of aspirin transfer to TG with an electron transport channel of O-Ti-C, which contribute to steer the enhanced adsorption. Furthermore, band structure and density of state display more densely and successive semimetal feature with a very slight band gap for TG, confirming the enhanced harvesting ability for wide wavelength regions of solar light. Consequently, the present investigation demonstrates by incorporating metal into PG frame, a strong adsorption material toward pharmaceutical contaminant could be achieved.

Urchin-like niobium oxide (U-Nb2O5) microspheres are obtained using a low-temperature hydrothermal method. The nanosized palladium (Pd) particles loading onto U-Nb2O5 (Pd/U-Nb2O5) microspheres are successfully prepared using a reflux method. X-ray diffraction results imply that the U-Nb2O5 and Pd/U-Nb2O5 microspheres belong to the orthorhombic phase, and Pd loading does not change the crystalline phase. The average size of nanosized Pd particles loaded is 4.25 nm. In addition, the valence states of Pd on the surface of the Pd/U-Nb2O5 microspheres are mainly of a Pd° form. The catalytic activity of the different loading amount Pd/U-Nb2O5 electrocatalysts is carried out in a 0.5 M KOH and 1 M ethylene glycol (EG). When the usage of palladium acetate is 10 mg (the mass ration of Pd to Nb2O5 is 10 %), the Pd/U-Nb2O5 electrocatalyst exhibits high catalytic activity for the electrooxidation of EG in an alkaline medium. The current density of EG electrooxidation on the Pd/U-Nb2O5 modified glassy carbon electrode is higher than that on commercial Pd/C (10 %). Moreover, the Pd/U-Nb2O5 electrocatalyst exhibits strong anti-CO poisoning ability and good stability for EG oxidation in alkaline medium. After 6000 s, the maintained current density on the Pd/U-Nb2O5 electrocatalyst is 12.7 times that on commercial Pd/C. This remarkable performance of the Pd/U-Nb2O5 electrocatalyst is owing to the synergistic effect between Pd and Nb2O5. The calculation results imply that the synergistic effect improves electron transfer.

Tryptophan 2,3-dioxygenase (TDO), an immunosuppressive enzyme, can involve in immune evasion and tumor tolerance. TDO inhibitors can boost the efficacy of chemotherapeutics by promoting immunity. Herein, a strategy to introduce a TDO inhibitor into Pt(IV) complexes for reversing tumor immune suppression was adopted. A mono-modified Pt(IV) complex, 3, displayed significant antitumor activity against human liver cancer cells. Flow cytometry study revealed that complex 3 could induce cell death via a mitochondrial-dependent apoptosis pathway and arrest the cell cycle at S phase. Furthermore, complex 3 was effective to enhance T-cell immune responses by inhibiting the TDO enzyme expression to block the kynurenine production and inactivating the downstream of aryl hydrocarbon receptor (AHR).

In order to study the cement hydration characteristics in the process of cement condensation, based on eddy current measuring technology and GMR (giant magnetoresistive sensor), it designed a non-contact cement-hydration-characteristics measuring device. As an advanced nondestructive detection technology, Eddy current detection is convenient and non-contact. And GMR has high sensitivity and good linearity. Combining eddy current detection technology with GMR in design, it successfully gets rid of electrode polarization in traditional contact testing method, and greatly improves the accuracy of cement impedance measurement, and it effectively solves the collision problem that the excitation coil needs high frequency and the measure must have high sensitivity. The measuring device mainly includes magnetic field, GMR sensor, and STM32F427 micro-computer data acquisition system. The testing results show that the device has high precision, good repeatability.