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Piezoelectric responsive molecular ferroelectrics have become a research hotspot due to their advantages of simple fabrication, environmental friendliness, light weight and good mechanical flexibility. Here we proposed a new kind of multipole rare earth molecular ferroelectric, ((nBu)4N)3[Ce(NO3)4(SCN)2]((CH3CH2CH2CH2)4N = tetrabutylammonium) (1). Compound 1 undergoes a high temperature ferroelectric phase transition at 408 K. It is worth noting that compound 1 has a narrow band gap of 2.61 eV, flexible switchable SHG effect, moderate spontaneous polarization Ps = 3.6 μC cm−2, and piezoelectric constant = 3 pC N−1. The results show that these findings provide ideas for exploring multifunctional rare earth molecular ferroelectrics with a piezoelectric effect. [ABSTRACT FROM AUTHOR]

• Selenium yeast addition increased the serum antioxidant capacity of Tibetan sheep. • Selenium addition increased DMI, FCR and nutrient digestibility. • Selenium retention and utilization rate were increased with selenium yeast addition. • The optimum level of selenium addition for Tibetan sheep was 0.4 mg/kg DM. Qinghai-Tibetan Plateau is a main area of selenium deficiency in the world, and local grazing livestock are affected by selenium deficiency. We conducted a metabolism trial of Tibetan sheep included adding selenium yeast at 0, 0.2, 0.4 and 0.8 mg Se/kg dry matter (DM) to the native pasture of Maqu county, Qinghai-Tibetan Plateau in 2017, to evaluated the impact of different levels of selenium addition on the selenium balance, nitrogen metabolism, nutrient digestibility and antioxidant status of native forage in Tibetan sheep. Our results showed that selenium balance, absorption and retention of Tibetan sheep were linearly affected by different selenium levels. However, the percentage of selenium retention is the highest when the selenium addition level is 0.4 mg/kg DM. The relationships between selenium addition levels and malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were quadratic. Based on the prediction equations, the most suitable selenium addition levels for MDA, SOD and T-AOC were 0.39, 0.36 and 0.47 mg/kg DM, respectively. Dietary supplementation of selenium could increase dry matter intake (DMI) and improve food conversion ratio (FCR), and the relationships between selenium addition level and DMI and FCR are both quadratic. Selenium addition could also increase apparent digestibility of NDF, ADF and EE with quadratic effects (P < 0.05). Based on the nutrient digestibility data and the prediction equations, we could get the most suitable selenium addition level is between 0.45 to 0.52 mg/kg DM. Furthermore, selenium supplementation could increase the intake and absorption of nitrogen with quadratic effects and the best predicted levels of selenium addition were 0.52 and 0.54 mg/kg DM, respectively. In summary, selenium supplementation is beneficial to the antioxidant status, digestibility and nitrogen metabolism of Tibetan sheep. Taking into account the predicted levels from different equations and our trial data, the optimum dosage of selenium yeast for Tibetan sheep was 0.4 mg Se/kg DM. [ABSTRACT FROM AUTHOR]

Carbon dots (CDs), a kind of burgeoning carbon-based nanomaterial, were widely used as high-efficiency lubricant additives for promoting the friction-reduction and anti-wear behaviors of green PEG-based lubricating oils. Undoubtedly, advances in CDs-based lubricant additives play a crucial role in enhancing their application prospect and utility value. Recent studies suggest that doping CDs with heteroatoms, especially multiple heteroatoms could remarkably promote their tribological performance. Therefore, the state-of-the-art N, B, and P-co-doped CDs (N,B,P-CDs) with a diameter of approximately 3.8 nm and composed of amorphous structures were synthesized by conveniently "one-step" pyrolyzing the corresponding carbon sources and dopants. Noticeably, the synthetic procedures of N,B,P-CDs were uninvolved in any pre-processing and post-processing techniques, showing favorable large-scale preparation potential. Adding suitable concentrations of N,B,P-CDs, the friction-reduction, anti-wear, and load-supporting functions of PEG200 base oil can be maximally increased by 38.1 %, 86.2 %, and 66.7 %, respectively, showing outstanding tribological performances. In addition, the tribological behaviors of N,B,P-CDs are evidently better than that of N,B-CDs and P-CDs under identical test conditions, exhibiting a multiatomic synergistic lubrication effect. According to the wear track surface analysis results and previous reports, the excellent tribological performance of N,B,P-CDs attributes to their favorable film-forming ability and nano-lubrication effect in the different friction stages. [Display omitted] • Novel N,B,P-CDs-based lubricant additives for PEG200 base oil were synthesized. • N,B,P-CDs as additives showed great anti-friction and anti-wear functions. • N,B,P-CDs possessed good multiatomic synergistic lubrication effect. • N,B,P-CDs have outstanding film-forming and nano-lubrication effects. [ABSTRACT FROM AUTHOR]

Abstract: Although great progress has been made for H‐bonds type molecular ferroelectrics, the systems accompanying with chiral to chiral phase transitions are still very spare. Here we display a new hydrogen bond type molecular ferroelectric, the salt of 1‐(1‐naphthyl) ethylammonium‐nopinate, 1, which undergoes a paraelectric–ferroelectric phase transition around 202 K from one chiral point group (P212121) to another chiral point group (P21). The electric hysteresis loop under 100 K directly indicates it is a potential ferroelectric material with maximum spontaneous polarization (Ps) 2.3 uC/cm2. X‐ray single crystal diffraction analysis shows that the significant hydrogen bond change along the b‐axis direction results net dipole moment and leads to the spontaneous polarization. The exceptional dielectric response in the vicinity of 202 K exhibits remarkable dielectric anomalies along the b‐axis direction than the other two directions. The strong SHG (second harmonic generation) signal (‐1.31) without obvious changes dependence on temperature further confirm the chiral to chiral structural phase transition. [ABSTRACT FROM AUTHOR]

Recently, energy and environmental crises have aggravated sharply, which results in the eco-friendly and high-efficiency polyethylene glycol (PEG) lubricating oils getting increasingly attention in lubrication. Advancing in PEG-based lubricating oils, especially their high-performance nano-additives is vitally important for energy conservation and reducing pollution. Therefore, a kind of surface and core dual-designed carbon dots (Zn,Cu,Fe-CDs -N) modified by ionic liquid groups ([AMIm][N(CF 3 SO 2) 2 ]) and doped by polymetallic atoms (Zn, Cu, and Fe) were first synthesized and creatively used as the nano-additives for the PEG200 base oil. Adding 1.0 wt% of Zn,Cu,Fe-CDs -N can endow the PEG200 base oil with optimal friction-reduction, anti-wear, and load-supporting performances, the maximal increase amplitudes of approximately 46.6 %, 66.3 %, and 125.0 %, respectively. Additionally, the tribological properties of Zn,Cu,Fe-CDs -N are without any weakening even under high load and long-time operating conditions, exhibiting good practicability and application prospects. Theoretical and experimental studies have illustrated the excellent tribological behaviors of Zn,Cu,Fe-CDs -N assigned to the synergy of film-forming and nano-lubrication effects. [Display omitted] • Polymetallic atom-doped carbon dots modified by ionic liquids were first prepared. • Zn,Cu,Fe-CDs -N as additives for PEG200 showed great tribological behaviors. • Great performance of Zn,Cu,Fe-CDs -N assigned to their multiple lubrication effect. [ABSTRACT FROM AUTHOR]

The tetracyanopyridine (4-cyanopyridine and 3-cyanopyridine) was reacted with rare earth nitrates (Ln = La, Gd, Er) under hydrothermal conditions by the Demko-Sharpless method, and four rare earth tetrazolium ionic compound were synthesized safely and effectively, named [Ln(H2O)8 ⋅ 3(p-TPD) ⋅ 2(p-HTPD) ⋅ 7H2O], (Ln = La( 1), Gd(2), Er (3), p-TPD = 4-tetrazolpyridine), [Ln(H2O)8 ⋅ 3(m-TPD) ⋅ 6H2O], (m-TPD = 3-tetrazolpyridine, Ln = Er(4)). These four rare earth tetrazolium ionic compounds were characterized by the single crystal X-ray diffraction, infrared spectroscopy, thermogravimetry, dielectric properties, X-ray powder diffraction. The X-ray single crystal structure analysis shows that the four rare earth tetrazolium compounds were all ionic, and the rare earth metal ions and ligands were in two different layers. The [Ln(H2O)8]3+ structure unit and p-TPD and water molecules formed a cationic layer through hydrogen bonding, while p-TPD and p-HTPD formed an anion layer through π-π stacking and hydrogen bonding. The cation layer and anion layer alternately form a regular network structure. Moreover, the dielectric properties tests indicate that the compounds 1, 2 have good dielectric properties. [ABSTRACT FROM AUTHOR]

[Display omitted] Chart of graphic abstract: (a) Figure Full wavelength scanning chart of PEG at at different concentrations; (b) Full wavelength scanning chart of SPS with different concentrations; (c) Polarization cures of gelatin with different concentrations; (d) Chart of gelatin concentration versus absorbance • We established the linear relationship between absorbency and the concentration of three organic nanomaterial additives based on the principle of ultraviolet spectrophotometry. • We eliminated the interference of copper and hydrogen ions in the plating solution on the detection results. • The linear correlation around 99% with the minimum detection limit of 1 mg/L was recorded for PEG. Due to the decomposition, condensation, and invalidation of organic additives in acid copper plating solution, it is hard to identify the effective concentration of additives, which causes difficulties in the prediction and grasping of the electroplating effect. To solve this problem, this paper established the linear relationship between absorbency and the concentration of organic additives based on the principle of ultraviolet spectrophotometry and the luminescence mechanism of the chromogenic agent and three organic additives after eliminating the interference of copper and hydrogen ions in the plating solution. The concentrations of polyethylene glycol (PEG), bis-(sodium sulfopropyl)-disulfide(SPS), and gelatin in the solution were analyzed quantitatively according to Law of Lambert-Beer. According to the results, the linear relationship between PEG's mass concentration and absorbency can be described as y = 0.01057 + 0.01372x, with a linear correlation of 0.9982, a relative error of about 0.56%-3.7%, and a minimum detection limit of 1 mg/L. The method adopted for detecting the SPS content records a relative error of around 0.817%-4.202% with the minimum detection limit of 2 μmol/L. The linear relationship between gelatin concentration and absorbancy is expressed as y = 0.02165x + 0.00932, in which the linear correlation r = 0.9906. [ABSTRACT FROM AUTHOR]

Background: Clinically, although chemotherapy is one of the most commonly used methods of treating tumors, chemotherapeutic drugs can induce autophagic flux and increase tumor cell resistance, leading to drug tolerance. Therefore, theoretically, inhibiting autophagy may improve the efficacy of chemotherapy. The discovery of autophagy regulators and their potential application as adjuvant anti-cancer drugs is of substantial importance. In this study, we clarified that Fangjihuangqi Decoction (FJHQ, traditional Chinese medicine) is an autophagy inhibitor, which can synergistically enhance the effect of cisplatin and paclitaxel on non-small cell lung cancer (NSCLC) cells. Methods: We observed the changes of autophagy level in NSCLC cells under the effect of FJHQ, and verified the level of the autophagy marker protein and cathepsin. Apoptosis was detected after the combination of FJHQ with cisplatin or paclitaxel, and NAC (ROS scavenger) was further used to verify the activation of ROS-MAPK pathway by FJHQ. Results: We observed that FJHQ induced autophagosomes in NSCLC cells and increased the levels of P62 and LC3-II protein expression in a concentration- and time-gradient-dependent manner, indicating that autophagic flux was inhibited. Co-localization experiments further showed that while FJHQ did not inhibit autophagosome and lysosome fusion, it affected the maturation of cathepsin and thus inhibited the autophagic pathway. Finally, we found that the combination of FJHQ with cisplatin or paclitaxel increased the apoptosis rate of NSCLC cells, due to increased ROS accumulation and further activation of the ROS-MAPK pathway. This synergistic effect could be reversed by NAC. Conclusion: Collectively, these results demonstrate that FJHQ is a novel late-stage autophagy inhibitor that can amplify the anti-tumor effect of cisplatin and paclitaxel against NSCLC cells. [ABSTRACT FROM AUTHOR]

Zero-dimensional perovskites have received extensive attention in recent years due to their unique structural properties, including large exciton binding energies, strong quantum confinement effects, and good stability. Target products were precisely constructed from existing organic–inorganic hybrid perovskite material phase-transition systems via exploiting the ideas of molecular design, modification, and assembly. Herein we report an organic–inorganic hybrid perovskite compound, [C6H18F6N3SbBr6] (1), with excellent reversible phase transition and dielectric switching properties. The symmetry of the structure was reduced upon introducing fluorine atoms to the ethylamine moiety. The results showed that compound 1 had a narrow bandgap of 2.90 eV and three distinct dielectric anomalies at ∼175.9, 205.9, and 257.5 K. UV-vis absorption spectra and density-functional theory (DFT) calculations confirmed this bandgap. It was revealed that the octahedral framework of inorganic [SbBr6]3− was the main contributor to this bandgap. This work highlights that the substitution of hydrogen atoms by halogens has important effects on the structural phase transition mechanism and physical properties of the synthesized product, therefore, it provides an effective strategy for the synthesis of novel organic–inorganic hybrid perovskite phase-transition materials. [ABSTRACT FROM AUTHOR]

Bistable switches (electrical switching between "ON" and "OFF" bistable states) have gradually developed into an ideal category of highly intelligent materials, due to their significant applications in optical technology, signal processors, data storage and other switchable media applications in the field of electrical devices. Here, we successfully designed and synthesized [(FC6H4C2H4NH3)2MCl4]n(FC6H4C2H4NH3+)=deprotonated 4‐fluoro‐ phenethylamine; M=Cd (1), Mn (2)), which realized the coupling of thermo‐dielectric switching characteristics, semi‐conductor characteristics and photo‐luminescent properties. DSC (differential scanning calorimetry) and dielectric measurements show that 1 is a sensitive dielectric bistable switch between the high dielectric (ON) and low dielectric (OFF) states. The temperature‐variable single crystal structure shows that the both 1 and 2 undergo a high‐temperature reversible phase transition around 383 K/380 K, which is caused by the order‐disordered transformation of organic cations and the slight distortion of the inorganic framework. In particular, 1 shows outstanding switchable dielectric behavior and semiconducting properties. Further, 1 and 2 emit strong green and yellow luminescence at 527 and 595 nm, respectively. [ABSTRACT FROM AUTHOR]

• 8 μm Cu-(SPS + HP) lithium copper foil with high tensile strength (∼570.57 MPa), high elongation (∼4.49%), and excellent surface performance were prepared by DC electrodeposition. • The fundamental reason for improving the mechanical properties of Cu-(SPS + HP) is the preferred orientation of the crystal plane and the phenomenon of large grains including small grains. • SPS and HP accelerated the reduction of Cu2+ in Cu-(SPS + HP) bath by synergistic promotion rather than antagonism. • A Cu-(SPS + HP) copper foil electrodeposition model was established, further clarifying the formation mechanism of different surface morphologies of copper foil. Copper foil is an important negative current collector material for lithium ion battery. Its mechanical properties and appropriate roughness have an important influence on the negative electrode and battery performance. Adding additives to the plating solution is an effective means to improve the performance of lithium copper foil. Here we prepared Cu-(SPS + HP) copper foil with a tensile strength of 570.57 MPa, elongation of 4.47%, and roughness of 0.812 μm. Moreover, the optical contact angle test shows that Cu-(SPS + HP) has the best surface wettability (the highest surface energy 50.62 mN/m). XRD and EBSD tests show that the fundamental reason for improving the mechanical properties of Cu-(SPS + HP) is the preferred orientation of the crystal plane (2 2 0) and the phenomenon of large grains including small grains. Besides, the electrochemical test of Cu-(SPS + HP) bath is conducted to determine the principle of additives in the plating process, cathodic reaction characteristics and electrocrystallization nucleation mechanism. Finally, we establish the electrodeposition model. The reaction behavior of SPS and HP in the plating process synergistically promoted the preparation of excellent performance lithium copper foil. [ABSTRACT FROM AUTHOR]

The high pressure and elastic properties of a hybrid ABX3-type perovskite, [C(NH2)3][Cd(HCOO)3] (CdGF), based on the A-site guest molecules are revealed via combining the high-pressure synchrotron X-ray diffraction experiments with density functional theory (DFT) calculations. The experimental results indicate that the anisotropic axial compressibilities are Ka = 2.8(4) and Kc = 20.9(10) TPa−1 within the pressure scope of 4.12 GPa, and calculations reveal the microscopic evolution of structure under pressure and demonstrate that this structural anisotropy is a consequence of the directional guest molecule and the cooperative effect of hydrogen bonding and octahedral tilting. In addition, full elastic constants of the perovskite were calculated to describe Young's moduli, shear moduli and Poisson's ratios. Notably, these discrete moduli are governed by the orientational guest molecule suggesting that the perovskite may display positive (negative) linear compression if it is flexible (rigid) along one principal axis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the synergistic effect of resveratrol on the bystander effect of TK/GCV suicide gene system in melanoma cells. Methods: The effect of resveratrol on the growth of B16 cells and the synergistic effect of resveratrol with or without GCV were detected by MTT assay and high content screening assay. The effect of resveratrol on GJIC function was detected by flow cytometry combined with fluorescence tracer and fluorescence microscope, and the expression of gap junction protein was detected by western blotting. Synergistic killing effect of resveratrol plus TK/GCV was tested in vivo using transplanted melanoma model. Results: In vitro, resveratrol can enhanced GJ function and upregulated Cx32 and Cx43 protein expression in B16 cells. Resveratrol synergized with GCV to kill mixed B16 melanoma cells (20% TK+ cells and 80% TK− cells) and to improve apoptosis rate of TK− cells (the bystander effect of TK system), and the synergistic action was reversed by the GJ inhibitor AGA. In vivo, when B16 cells were mixed with 30% TK+ B16 cells, significantly reduced tumor weight and volume were observed after combinational treatment with resveratrol plus GCV as compared with GCV or resveratrol treatment alone. Conclusions: Resveratrol could synergistically enhance the killing effect of TK/GCV suicide gene system in melanoma B16 cells and transplanted melanoma. It might be a promising adjuvant of TK/GCV therapy. [ABSTRACT FROM AUTHOR]

Despite its low transfer efficiency, suicide gene therapy with HSV-TK is known for its bystander killing effect. The connexin-based gap junction is believed to mediate the bystander effect. Recently, we found that resveratrol, a polyphenol compound, increased the expression of Cx26 and Cx43, which are connexins and important constituents of gap junctions, in murine hepatoma cells. Hypothetically, the resveratrol-induced upregulation of gap junctions may improve the bystander effect that HSV-TK/GCV has on hepatoma cells. Our present investigation revealed that resveratrol could enhance intercellular communication at the gap junctions in CBRH7919 hepatoma cells and thereby enhance the bystander killing effect of GCV on CBRH7919TK cells. However, inhibition of gap junction using its long-term inhibitor alpha-glycyrrhetinic acid had a negative influence on the bystander effect of gene therapy with HSV-TK/GCV. In addition, combined resveratrol and GCV treatment in tumor-bearing mice with CBRH7919TK and CBRH7919WT cells at a ratio of 2:3 resulted in a significant decrease in the volume and weight of the tumor in comparison to GCV or only resveratrol. The present results demonstrate that resveratrol can enhance the bystander effect exerted by the HSV-TK/GCV system by enhancing connexin-mediated gap junctional communication. [ABSTRACT FROM AUTHOR]

Berberine is a natural compound extracted from Coptidis rhizoma, and accumulating proof has shown its potent anti-tumor properties with diverse action on melanoma cells, including inhibiting cancer viability, blocking cell cycle and migration. However, the mechanisms of berberine have not been fully clarified. In this study, we identified that berberine reduced the migration and invasion capacities of B16 cells, and notably altered pluripotency of epithelial to mesenchymal transition associated factors. We found that berberine also downregulation the expression level of p-PI3K, p-AKT and retinoic acid receptor α (RARα) and upregulation the expression level of retinoic acid receptor β and γ (RARβ and RARγ). These effects of PI3 kinase inhibitor LY294002 treatment mimicked Berberine treatment except the expression level of RARγ. Moreover, Western blot analysis showed that the decreased PI3K and AKT phosphorylation, increased the epithelial maker E-cadherin, and upregulation level of RARβ while decreased the mesenchymal markers N-cadherin and downregulation level of RARα by incubation with LY294002 in mouse melanoma B16 cells. In conclusion, Our study reveal that berberine can reverse the epithelial to mesenchymal transition of mouse melanoma B16 cells and may be a useful adjuvant therapeutic agent in the treatment of melanoma through the PI3K/Akt pathway and inactivation PI3K/AKT could regulate RARα/RARβ expression. [ABSTRACT FROM AUTHOR]

The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV). This effect is reported to be mediated by gap junctional intercellular communication (GJIC), and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA), a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy. [ABSTRACT FROM AUTHOR]

Metal-free molecular compound (PIPz)(NH 4 I 3)∙H 2 O (1 ; PIPz = Piperazinium) undergoes a phase transition of Pbcn ↔ Pbcm attributed to the reorientation of the PIPz2+ and H 2 O as well as the disorder of NH+ and H 2 O. [Display omitted] • Metal-free molecular compound (PIPz)(NH 4 I 3)∙H 2 O undergoes a first-order phase transition at low temperature and exhibits an entropy change Δ S = 4.58 J mol−1K−1. • Experimental results indicate structure change from Pbcn to Pbcm attributed to the reorientation of the PIPz2+ and H 2 O as well as the disorder of NH+ and H 2 O. The metal-free molecular compound (PIPz)(NH 4 I 3)∙H 2 O (1 ; PIPz = Piperazinium) has been systematically characterized by a series of experimental characterization. Results indicate that compound 1 undergoes a first-order phase transition at low temperature 280.14 K. The single-crystal X-ray diffraction analyses reveal that the structure of compound 1 transforms from Pbcn to Pbcm during the phase transition, accompanying with reorientation and disorder of the PIPz2+ and H 2 O molecules. [ABSTRACT FROM AUTHOR]

Efficient building instance segmentation is necessary for many applications such as parallel reconstruction, management and analysis. However, most of the existing instance segmentation methods still suffer from low completeness, low correctness and low quality for building instance segmentation, which are especially obvious for complex building scenes. This paper proposes a novel unsupervised building instance segmentation (UBIS) method of airborne Light Detection and Ranging (LiDAR) point clouds for parallel reconstruction analysis, which combines a clustering algorithm and a novel model consistency evaluation method. The proposed method first divides building point clouds into building instances by the improved kd tree 2D shared nearest neighbor clustering algorithm (Ikd-2DSNN). Then, the geometric feature of the building instance is obtained using the model consistency evaluation method, which is used to determine whether the building instance is a single building instance or a multi-building instance. Finally, for multiple building instances, the improved kd tree 3D shared nearest neighbor clustering algorithm (Ikd-3DSNN) is used to divide multi-building instances again to improve the accuracy of building instance segmentation. Our experimental results demonstrate that the proposed UBIS method obtained good performances for various buildings in different scenes such as high-rise building, podium buildings and a residential area with detached houses. A comparative analysis confirms that the proposed UBIS method performed better than state-of-the-art methods. [ABSTRACT FROM AUTHOR]

• Two new complexes have been synthesized by ligand 2-HTP (2-HTP = 2-(1H-1, 2, 4-triazol-3-yl)pyridine) reaction with different catalysts. • Experiments reveal that hydrogen bonding and π-π interactions exist in structure of complex 1 , while only π-π interaction exists in complex 2 , leading to the complex 1 has stronger intermolecular interactions than complex 2. Two novel metal complexes C 7 H 10 CoN 4 O 6 S (1) and C 9 H 8 CuN 4 O 2 (2) were synthesized by ligand 2-HTP (2-HTP = 2-(1H-1, 2, 4-triazol-3-yl)pyridine) reaction with different catalysts CoSO 4 ·7H 2 O and Cu(CH 3 COO) 2 ·H 2 O, respectively. Single crystal X-ray diffraction experiments reveal that the symmetry of complexes 1 and 2 respective belong to high centrosymmetric space group C 2/ c with point group C 2 h 6 and low centrosymmetric space group P 2 1 / n with point group C 2 h 5 , however, the symmetric elements (E , C 2 , i , σ h) remains unchanged. Meanwhile, hydrogen bonding and π-π interactions exist in structure of complex 1 , while only π-π interaction exists in complex 2. In addition, Hirshfeld surface analyses, especially d e , d norm and decomposed fingerprint plots, further indicate complex 1 has stronger intermolecular interactions than complex 2 , which leads to complexes 1 and 2 form a three-dimensional network and a one-dimensional chain structures, respectively. [ABSTRACT FROM AUTHOR]

The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified N-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions—mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells. [ABSTRACT FROM AUTHOR]

Chemoresistance is a major limiting factor that impairs the outcome of non-small cell lung cancer (NSCLC) chemotherapy. Paclitaxel (Tax) induces protective autophagy in NSCLC cells, leading to the development of drug resistance. We recently identified a new autophagy inhibitor (alpha-hederin) and hypothesized that it may promote the killing effect of Tax on NSCLC cells. We found that alpha-hederin (α-Hed) could block late autophagic flux in NSCLC cells by altering lysosomal pH and inhibiting lysosomal cathepsin D maturation. Combination treatment of α-Hed and Tax synergistically reduced NSCLC cell proliferation and increased NSCLC cell apoptosis compared with treatment with α-Hed or Tax alone. Furthermore, α-Hed plus Tax enhanced the accumulation of intracellular reactive oxygen species (ROS) in NSCLC cells, while the ROS inhibitor N-acetylcysteine reversed the inhibitory effect of the combination treatment. Our findings suggest that α-Hed can increase the killing effect of Tax on NSCLC cells by promoting ROS accumulation, and that combining α-Hed with classical Tax represents a novel strategy for treating NSCLC. [ABSTRACT FROM AUTHOR]