Adsorption Properties of Diatomite Minerals on Glyceryl Monostearate for Antifogging of the Plastic Film.

Adding an appropriate amount and the stable precipitation of surfactant on the inner surface of agricultural plastic greenhouse films can prevent the formation of water droplets on the inner surface of the film to reduce its harmful effects in the process of plant cultivation and production. In this work, for the stable precipitation of the surfactant glycerol monostearate, diatomite minerals from three origins in China were compared through structural analysis and adsorption performance. The effects of acid treatments and alkali treatments on the mineral structure were studied, and the adsorption mechanism of glycerol monostearate was further investigated. The results show that the structural characteristics of Jilin diatomite are more suitable as adsorbents for glyceryl monostearate adsorption. Because diatomite is resistant to acids but not alkalis, when diatomite is treated with an alkali, impurities on its surface can be removed and the hydroxyl group and specific surface area can be greatly increased. The adsorption capacity of glycerol stearate was increased to 218.4 mg/g, or 32.08%, over its pretreatment level. The results show that this is mainly the result of physical adsorption caused by van der Waals force imbalance and chemisorption caused by a small number of hydrogen bonds. In addition, the dripping performance of this composite dripping film with mineral diatomite was better than that of the commercial dripping film, which provided a theoretical basis for efficient mineral slow-release drip irrigation composite film.

A novel highly dispersed calcium silicate hydrate nanosheets for efficient high-concentration Cu2+ adsorption.

Currently, the low cost and effective purification toward heavy metal ions in wastewater has garnered global attention. Herein, we used hydrothermal method to prepare highly dispersed calcium silicate hydrate in fluorite tailings. And the stacking thickness of calcium silicate hydrate layered morphology was less than 5 nm. For high concentration Cu2+ purification investigation in wastewater, we found that the equilibrium adsorption capacity reached 797.92 mg/g via the CSH with 3:2 Ca/Si molar ratio, be 1.43-21.8 times than that of reported data. Therein, the metal-metal exchange and deposition are the primary pathways for Cu2+ adsorption, and electrostatic attraction is the secondary pathway. And the relative ∼100 % removal rate of high-concentration Ni2+ and Cr3+ ions were confirmed via CSH prepared from different tailings. This method offers a cost-effective way to utilize tailings for preparing highly efficient adsorbents toward HMIs removal in wastewater.

Highly efficient recovery of Zn (II) from zinc-containing wastewater by tourmaline tailings geopolymers to in-situ construct nanoscale ZnS for the photodegradation of tetracycline hydrochloride.

While treating zinc-containing wastewater, recovering zinc for reuse as a secondary resource has significant environmental and economic benefits. Herein, based on the alkali-activated tourmaline tailings geopolymers (TTG) after adsorption of zinc ions (Zn (II)), a series of new composites with in-situ construction ZnS nanoparticles on TTG (ZnS/TTG) were synthesized, and used as photocatalysts for the photodegradation of tetracycline hydrochloride (TCH) in solution. Specifically, ZnS nanoparticles were uniformly and stably distributed in the layered structure of TTG, interweaving with each other to generate an interfacial electric field, which could induce more photocarrier generation. Meanwhile, TTG acted as an electron acceptor to accelerate the electron transfer at the interface, thus enhancing the photodegradation activity for TCH. The active radical quenching experiments combined with the ESR indicated that the active species produced during the photocatalytic degradation of TCH by ZnS/TTG composites were •O2- and photogenerated h+. When the initial concentration of Zn (II) was 60 mg/L, the synthesized 60-ZnS/TTG composites (0.5 g/L) reached 91.53% degradation efficiency of TCH (10 mg/L) at pH = 6. Furthermore, the possible pathways and mechanism of 60-ZnS/TTG composites photodegraded TCH were revealed with the aid of degraded intermediates. This report not only proposed valuable references for reusing heavy metal ions and removing TCH from wastewater, but also provided promising ideas for realizing the conversion of used adsorbents into high-efficiency photocatalysts.

[Simultaneous determination of four N-lauryl amino acid surfactants in facial cleansers by high performance liquid chromatography-ultraviolet detection].

Significant developments have recently been achieved in the field of N-lauryl amino acid (NLAA) surfactants derived from renewable resources. Compared with conventional surfactants, NLAAs exhibit remarkable surfactant properties, exceptional biodegradability, good biocompatibility, and high safety profiles. These attributes have led to the widespread use of NLAAs in personal-care products. The detection methods employed for NLAAs include two-phase titration (TT), spectrophotometric analysis (SA), and high performance liquid chromatography (HPLC). However, because both TT and SA measure the total concentration of anionic active matter, identifying and quantifying individual compounds in a sample containing multiple anionic surfactants is impossible. The presence of cationic surfactants in the sample also introduces interferences, which lead to significant errors. Compared with TT and SA, HPLC offers direct and rapid testing procedures. However, compounds with no or weak UV-visible light absorption exhibit low sensitivity when detected by UV, necessitating the use of detectors such as differential refractive index detectors (RIDs), evaporative light scattering detectors (ELSDs), or charged aerosol detectors (CADs). Most HPLC users consider UV light as the fundamental configuration of the instrument, and other detectors are less commonly employed. Therefore, establishing a new HPLC method suitable for the UV detection of NLAAs is of practical significance. In this study, a novel HPLC-UV method was developed for the simultaneous detection of N-lauryl glutamine (LG), N-lauryl glycine (LC), N-lauryl alanine (LA), and N-lauryl sarcosine (LS) by optimizing the mobile-phase composition and selecting an appropriate chromatographic column and detection wavelength. The samples were mixed with acetonitrile-0.10% H3PO4 aqueous solution (60∶40, v/v) and sonicated for 10 min, then stayed at room temperature for 5 min. Subsequently, the mixture was filtered through a 0.22 µm filter membrane and separated on an Agilent Eclipse Plus C18 column (150 mm×4.6 mm, 5 µm). The mobile phase used for separation consisted of acetonitrile-0.10% H3PO4 aqueous solution at a flow rate of 1.0 mL/min. The detection wavelength was set at 205 nm, and the injection volume was 10 µL. The results demonstrated that the four NLAAs exhibited good linearity in the range of 2.0-800.0 mg/L, with correlation coefficients (r)≥0.9995. The limits of detection (LODs) ranged from 0.17 to 0.49 mg/L, and limits of quantification (LOQs) ranged from 0.57 to 1.63 mg/L. The relative standard deviations (RSDs) for precision, repeatability, and stability over 24 h were all below 2.0%. Using this method, the NLAA contents of five facial-cleanser products were determined. The results demonstrated that all five samples contained one or more NLAAs, and the total NLAA contents ranged from 64.58 to 97.01 mg/g. The five spiked-sample recoveries of the NLAAs at four different spiked levels (0.60, 4.50, 15.00, 24.00 mg/g) ranged from 94.3% to 107.4%, indicating satisfactory accuracy. However, the actual NLAA composition and label for one facial-cleanser product were not consistent with our test results. This finding demonstrates the necessity of strengthening market monitoring through testing. The proposed method has the advantages of simple pretreatment, rapid testing, good precision, high accuracy, and appropriate stability. Thus, it is suitable for the determination of NLAA contents in facial cleansers and provides an effective technical reference for the raw-material purity assessment, synthetic yield detection, and product quality control of this type of surfactant.

Removal of Aflatoxin B1 and Zearalenone in Mixed Aqueous Solution by Palygorskite-Montmorillonite Materials In Situ Prepared from Palygorskite Mineral.

In view of the animal feeds inevitably contaminated by multiple mycotoxins, eco-friendly and efficient palygorskite-montmorillonite (Pal-Mt) materials were prepared to remove polar aflatoxin B1 (AFB1) and weak polar zearalenone (ZEN) from mixed mycotoxins aqueous solution. The adsorption properties and bonding mechanisms between Pal-Mt materials and mycotoxins (AFB1 and ZEN) were investigated systematically. The as-prepared Pal-Mt showed excellent adsorption capacity for AFB1 and ZEN in single- and binary-mycotoxin systems, indicating the effectiveness of Pal-Mt acting as multiple mycotoxin adsorbents. The kinetics of adsorption for ZEN was fast due to the adsorption on the external surface (film and intraparticle diffusion), while AFB1 molecules permeated into mesopores after the external adsorption for the more planar structure. Adsorption isotherms demonstrated that heterogeneous surface adsorption appeared between Pal-Mt and AFB1, and monolayer adsorption occurred on Pal-Mt and ZEN for different polarities of mycotoxins. Thermodynamic parameters illustrated that the adsorption process of both AFB1 and ZEN onto Pal-Mt was spontaneous and endothermic. The adsorption mechanism studies suggested that hydrogen bonding, electrostatic attraction, calcium bridging linkage, and ion-dipole played fundamental roles in the interaction between Pal-Mt and these two mycotoxins.

Microalgae removal technology for the cold source of nuclear power plant: A review.

In the past three decades, nuclear energy has gained much attention as carbon-free electricity. Due to the supply of cooling water in nuclear power plant, large amount of waste heat will increase the water temperature, promote the microalgae and cyanobacteria propagation and increase the chance of red tide. Excess phytoplankton of cool source will result in abnormal operation of cooling system, even core overheating and nuclear leakage. Consequently, it is very important to remove microalgae and cyanobacteria from cold source of nuclear power plants. This review summarizes the formation mechanism and monitoring methods of red tide, compares the advantages and disadvantages of traditional microalgae removal technology including physical, chemical and biological methods. Furthermore, the improved electrochemical method and micro-nano bubble method are introduced in detail. Their combination is considered to be a low-cost, efficient and environmentally-friendly technology to prevent and control red tides for cold source of nuclear power plant.

Preparation of Iron Ore Tailings-Based Superhydrophobic Coatings.

In this study, ball mill pretreated iron ore tailings were modified with tetraethoxysilane (TEOS) and hexadecyltrimethoxysilane (HDTMS) to obtain iron ore tailings/polysiloxane (IOT/POS) superhydrophobic powders, which were subsequently mixed with chloroprene rubber solution (CRS) to prepare durable superhydrophobic composite coatings. The effect of HDTMS amount and reaction time on the wettability of the superhydrophobic powder was investigated. The influence of the superhydrophobic powders concentration on the wettability of the composite coatings as well as the degree of damage of the superhydrophobicity of the composite coating was analyzed by using the sandpaper abrasion and tape peeling tests. Further, SEM and FTIR were used to analyze the formation mechanism of the IOT/POS superhydrophobic powders and coatings. The results showed for an HDTMS amount of 2.5 mmol and reaction time of 4 h, the contact angle of the IOT/POS powder was 157.3 ± 0.6°, whereas the slide angle was determined to be 5.9 ± 0.8°. For an IOT/POS powder content of 0.06 g/mL in CRS, the contact angle value of the superhydrophobic composite coating was 159.2 ± 0.5°, whereas the slide angle value was 5.5 ± 0.8°. The superhydrophobic composite coating still maintained the superhydrophobicity after the sandpaper abrasion and tape peeling tests, which indicated the iron ore tailings solid waste has the potential to prepare superhydrophobic coatings.

Ultrafine Grinded and Silane Grafted Iron Ore Tailings as Reinforcing Filler of Styrene Butadiene Rubber.

In order to realize the high value-added resource utilization of solid waste and reduce the cost of rubber manufacturing, iron ore tailings (IOTs) were used as raw material to prepare a reinforcing filler of rubber through ultrafine grinding and surface organic modification techniques. We studied the effects of ball mill grinding conditions on the particle size and distribution of grinded iron ore tailings (G-IOTs). The effects of bis-(triethoxy-silyl-propyl)-tetrasulfide (Si69)-modified G-IOT (Si69-G-IOT) loading levels on the cure characteristics, static mechanical and dynamic mechanical properties of the styrene butadiene rubber (SBR) composites were also explored in this paper. The grinding and modification mechanism of IOTs and the combination of filler and SBR matrix were explored by grinding simulation of population balance model, X-ray diffraction analysis, Fourier transform infrared spectroscopy and scanning electron microscopy. The results showed that when grinding IOTs at 2000 r/min for 150 min, the particle size distribution of the resulting G-IOTs was the narrowest, with a D90 value of 4.42 µm. The tensile strength and elongation at break of SBR filled with 120 phr Si69-G-IOT were 14.97 MPa and 596.36%, respectively.

Tracking the redox reaction-induced reconstruction of NiAu nanoparticles via environmental scanning transmission electron microscopy.

Atmosphere-related atom migration and phase reconstruction are an easy way for optimizing the catalytic activity of a bimetallic catalyst. Herein, the structure evolutions of NiAu nanoparticles under oxidative and reductive environments are investigated via combining identical location and in situ environmental scanning transmission electron microscopy. During oxidation, a NiO layer first forms and the redispersion of Ni and Au atoms yields a Ni@Au@NiO multi-shell structure at 350 °C. Further, Ni and Au segregate into an Au-NiO hybrid structure at 600 °C. During reduction, Au atoms disperse over the particle surface forming a NiAu alloy shell with scattered Au atoms/clusters. In situ observation further discloses that the reduction changes the local structural ordering from Ni3Au to NiAu alloy. Very interestingly, the reduced NiAu exhibits promoted activity over oxidized ones for the CO-NO reaction. Density functional theory calculations further reveal the structure-property relationships of CO, NO, and O adsorbates on NiAu alloy surfaces. This study is beneficial for understanding the atmosphere-related evolution behaviors of bimetallic systems, thereby inspiring the catalytic surface optimization.

Preparation of Sepiolite Nanofibers Supported Zero Valent Iron Composite Material for Catalytic Removal of Tetracycline in Aqueous Solution.

The heavy use of antibiotics in medicine, stock farming and agriculture production has led to their gradual accumulation in environmental media, which poses a serious threat to ecological environment and human safety. As an efficient and promising catalyst for the degradation of antibiotics, nanoscale zero valent iron (nZVI) has attracted increasing attention in recent years. In this study, sepiolite nanofiber supported zero valent iron (nZVI/SEP) composite was prepared via a facile and environmentally friendly method. The nZVI particles (with size of 20-60 nm) were dispersed evenly on the surface of sepiolite nanofibers, and the catalytic performance for the removal of tetracycline hydrochloride (TC-HCl) in aqueous system was investigated. The effect of nZVI loading amount, catalyst dosage, H2O2 concentration and pH on the removal efficiency of TC-HCl were studied. It was revealed that the sepiolite supporter effectively inhibited the agglomeration of nZVI particles and increased the contact area between contaminant and the active sites, resulting in the higher catalytic performance than pure nZVI material. The TC-HCl removal efficiency of nZVI/SEP composite was up to 92.67% when TC-HCl concentration of 20 mg/L, catalyst dosage of 1.0 g/L, H2O2 concentration of 1.0 mM, pH value of 7. Therefore, the nZVI/SEP composites possess high catalytic activity for TC-HCl removal and have great application prospects in antibiotic wastewater treatment.

A Facile Fabrication of ZnFe2O4/Sepiolite Composite with Excellent Photocatalytic Performance on the Removal of Tetracycline Hydrochloride.

The excellent photo-response of ZnFe2O4 in the visible light region makes it a promising catalyst, whereas some defects like serious particle agglomeration and easy recombination of photo-generated electron-hole pairs hinder its application. In this work, the ZnFe2O4/sepiolite (ZF-Sep) composites were synthesized using a co-precipitation method. The obtained ZF-Sep composites were characterized by XRD, SEM, TEM, FT-IR, XPS, BET, VSM and DRS. Moreover, the photocatalytic performance was evaluated by the tetracycline hydrochloride removal efficiency under simulated visible light illumination. The results displayed that the ZnFe2O4 with average sizes about 20 nm were highly dispersed on sepiolite nanofibers. All the composites exhibited better photocatalytic performance than pure ZnFe2O4 due to the synergistic effect of the improvement on the agglomeration phenomenon of ZnFe2O4 and the reduction on the recombination rate of photo-generated electrons and holes. The optimum removal efficiency was that of the ZF-Sep-11 composite, which reached 93.6% within 3 h. Besides, the composite exhibited an excellent stability and reusability. Therefore, ZF-Sep composite is a promising catalyst for the treatment of wastewater contained antibiotics.

PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer.

High-grade serous ovarian cancers (HGSOC) represent the most common subtype of ovarian malignancies. Due to the frequency of late-stage diagnosis and high rates of recurrence following standard of care treatments, novel therapies are needed to promote durable responses. We investigated the anti-tumor activity of CD3 T cell engaging bispecific antibodies (TCBs) directed against the PAX8 lineage-driven HGSOC tumor antigen LYPD1 and demonstrated that anti-LYPD1 TCBs induce T cell activation and promote in vivo tumor growth inhibition in LYPD1-expressing HGSOC. To selectively target LYPD1-expressing tumor cells with high expression while sparing cells with low expression, we coupled bivalent low-affinity anti-LYPD1 antigen-binding fragments (Fabs) with the anti-CD3 scFv. In contrast to the monovalent anti-LYPD1 high-affinity TCB (VHP354), the bivalent low-affinity anti-LYPD1 TCB (QZC131) demonstrated antigen density-dependent selectivity and showed tolerability in cynomolgus monkeys at the maximum dose tested of 3 mg/kg. Collectively, these data demonstrate that bivalent TCBs directed against LYPD1 have compelling efficacy and safety profiles to support its use as a treatment for high-grade serous ovarian cancers.

Inhibition of MDM2 Promotes Antitumor Responses in p53 Wild-Type Cancer Cells through Their Interaction with the Immune and Stromal Microenvironment.

p53 is a transcription factor that plays a central role in guarding the genomic stability of cells through cell-cycle arrest or induction of apoptosis. However, the effects of p53 in antitumor immunity are poorly understood. To investigate the role of p53 in controlling tumor-immune cell cross-talk, we studied murine syngeneic models treated with HDM201, a potent and selective second-generation MDM2 inhibitor. In response to HDM201 treatment, the percentage of dendritic cells increased, including the CD103+ antigen cross-presenting subset. Furthermore, HDM201 increased the percentage of Tbet+Eomes+ CD8+ T cells and the CD8+/Treg ratio within the tumor. These immunophenotypic changes were eliminated with the knockout of p53 in tumor cells. Enhanced expression of CD80 on tumor cells was observed in vitro and in vivo, which coincided with T-cell-mediated tumor cell killing. Combining HDM201 with PD-1 or PD-L1 blockade increased the number of complete tumor regressions. Responding mice developed durable, antigen-specific memory T cells and rejected subsequent tumor implantation. Importantly, antitumor activity of HDM201 in combination with PD-1/PD-L1 blockade was abrogated in p53-mutated and knockout syngeneic tumor models, indicating the effect of HDM201 on the tumor is required for triggering antitumor immunity. Taken together, these results demonstrate that MDM2 inhibition triggers adaptive immunity, which is further enhanced by blockade of PD-1/PD-L1 pathway, thereby providing a rationale for combining MDM2 inhibitors and checkpoint blocking antibodies in patients with wild-type p53 tumors. SIGNIFICANCE: This study provides a mechanistic rationale for combining checkpoint blockade immunotherapy with MDM2 inhibitors in patients with wild-type p53 tumors.

LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors.

PURPOSE: Targeting RAF for antitumor therapy in RAS-mutant tumors holds promise. Herein, we describe in detail novel properties of the type II RAF inhibitor, LXH254. EXPERIMENTAL DESIGN: LXH254 was profiled in biochemical, in vitro, and in vivo assays, including examining the activities of the drug in a large panel of cancer-derived cell lines and a comprehensive set of in vivo models. In addition, activity of LXH254 was assessed in cells where different sets of RAF paralogs were ablated, or that expressed kinase-impaired and dimer-deficient variants of ARAF. RESULTS: We describe an unexpected paralog selectivity of LXH254, which is able to potently inhibit BRAF and CRAF, but has less activity against ARAF. LXH254 was active in models harboring BRAF alterations, including atypical BRAF alterations coexpressed with mutant K/NRAS, and NRAS mutants, but had only modest activity in KRAS mutants. In RAS-mutant lines, loss of ARAF, but not BRAF or CRAF, sensitized cells to LXH254. ARAF-mediated resistance to LXH254 required both kinase function and dimerization. Higher concentrations of LXH254 were required to inhibit signaling in RAS-mutant cells expressing only ARAF relative to BRAF or CRAF. Moreover, specifically in cells expressing only ARAF, LXH254 caused paradoxical activation of MAPK signaling in a manner similar to dabrafenib. Finally, in vivo, LXH254 drove complete regressions of isogenic variants of RAS-mutant cells lacking ARAF expression, while parental lines were only modestly sensitive. CONCLUSIONS: LXH254 is a novel RAF inhibitor, which is able to inhibit dimerized BRAF and CRAF, as well as monomeric BRAF, while largely sparing ARAF.

Effect of Palygorskite on the Sintering Process and Kinetics of Bone China.

The sintering process of bone china bodies containing 0, 2, 4, and 6 wt % palygorskite was studied by X-ray diffraction (XRD), differential scanning calorimetry and thermogravimetry (DSC/TG), and dilatometric tests. According to the XRD and DSC/TG results, the increment of palygorskite increased the content of the amorphous phase and reduced the formation temperature of the early liquid phase in the bone china bodies. The shrinkage data showed that the starting sintering temperature and maximum shrinkage temperature of bone china bodies in the stage of liquid-phase sintering decreased by 20 and 15 °C via adding 6 wt % palygorskite, respectively. Also, the maximum shrinkage rose with increasing amount of palygorskite. Moreover, the kinetic analysis of shrinkage data was conducted by the Salem model. The value of the mechanism-characteristic exponent, m, rose from 0.62 to 0.91 by adding 6 wt % palygorskite. In addition, with increasing palygorskite, the value of activation energy, E a, linearly reduced, and the value of rate constant A increased.

Functionalized nanoflower-like hydroxyl magnesium silicate for effective adsorption of aflatoxin B1.

Aflatoxin B1 (AFB1), which is widely found in food and feed, poses a serious threat to the health of human and livestock. In this work, functionalized nanoflower-like hydroxyl magnesium silicate (FNHMS) was synthesized for adsorption of AFB1. First, bulk magnesium silicate (MS) was converted into nanoflower-like hydroxyl magnesium silicate (NHMS) by hydroxylation. Cetyltrimethylammonium bromide (CTMAB) modification then enhanced the hydrophobicity and the affinity to AFB1 of NHMS. The adsorption performance for AFB1 followed the order of MS < NHMS < FNHMS, and the adsorption performance increased with the increase of the dose of CTMAB. Isothermal adsorption analysis indicated that the surface of FNHMS was heterogeneous. The adsorption capacity of FNHMS-0.4 to AFB1 was estimated to be 27.34 mg g-1 and 28.61 mg g-1 by Freundlich and Dubinin-Radushkevich isotherm adsorption model, respectively. By analyzing the adsorption kinetics and adsorption thermodynamics, both physical adsorption and chemisorption existed in the process of AFB1 being adsorbed on FNHMS-0.4. Adsorption mechanisms analysis indicated that the adsorption followed the adsorption site priority of H > O > Mg. This work demonstrates that FNHMS could be a promising adsorbent for removal of AFB1.

Tourmaline-Modified FeMnTiO x Catalysts for Improved Low-Temperature NH3-SCR Performance.

Low temperature NH3 selective catalytic reduction (NH3-SCR) technology is an efficient and economical strategy for cutting NO x emissions from power-generating equipment. In this study, a novel and highly efficient NH3-SCR catalyst, tourmaline-modified FeMnTiO x is presented, which was synthesized by a simple one-step sol-gel method. We found that the amount of tourmaline has an important impact on the catalytic performance of the modified FeMnTiO x-based catalysts, and the NO x conversion exceeded 80% from 160 to 380 °C with the addition of 5 wt % tourmaline. Compared with the pure FeMnTiO x, the catalytic efficiency at a temperature below 100 °C was increased by nearly 18.9%, and the operation temperature window was broadened significantly. The enhanced catalytic performance of the FeMnTiO x catalyst was mainly attributed to the small spherical nanoparticles structure around the tourmaline powders, resulting in the increased content of Mn3+, Mn4+, and chemical oxygen on the catalytic surface. These as-developed tourmaline-modified FeMnTiO x materials have been demonstrated to be promising as a new type highly efficient low temperature NH3-SCR catalyst.

The Preparation and Properties of Porous Sepiolite Ceramics.

In this paper, a new type of porous ceramics was prepared using the raw sepiolite mineral. The porous ceramics was shaped by the dry pressing method and sintered in the range of 700 ~ 1200 °C. The temperature-microstructure evolution and the properties of porous sepiolite ceramics were investigated by thermo gravimetric and differential thermal analyses (TG-DTA), X-ray diffraction (XRD), bending strength, compressive strength, scanning electron microscopy (SEM) and mercury intrusion porosimeter (MIP). The sintering kinetics of the porous ceramics from sepiolite was investigated by means of stepwise isothermal dilatometry (SID). The mechanical properties improved with the increasing sintering temperature, and the bending strength and compression strength reached a maximum of 52 MPa and 32 MPa respectively at 1200 °C. The porosity increased with the sintering temperature until 1100 °C attaining the value of 55.40% and then decreased to a value of 46.48% at 1200 °C. The main crystal phases of the porous ceramics were akermanite and diopside. At 1200 °C, the pores inside the ceramics basically follows a unimodal distribution, which was mainly located near 553 nm. The sintering activation energy of porous sepiolite ceramics was measured by step isothermal thermal expansion with a value of 791.42 kJ/mol in the range of 1000 °C to 1200 °C.

Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation.

PURPOSE: The selective MET inhibitor capmatinib is being investigated in multiple clinical trials, both as a single agent and in combination. Here, we describe the preclinical data of capmatinib, which supported the clinical biomarker strategy for rational patient selection. EXPERIMENTAL DESIGN: The selectivity and cellular activity of capmatinib were assessed in large cellular screening panels. Antitumor efficacy was quantified in a large set of cell line- or patient-derived xenograft models, testing single-agent or combination treatment depending on the genomic profile of the respective models. RESULTS: Capmatinib was found to be highly selective for MET over other kinases. It was active against cancer models that are characterized by MET amplification, marked MET overexpression, MET exon 14 skipping mutations, or MET activation via expression of the ligand hepatocyte growth factor (HGF). In cancer models where MET is the dominant oncogenic driver, anticancer activity could be further enhanced by combination treatments, for example, by the addition of apoptosis-inducing BH3 mimetics. The combinations of capmatinib and other kinase inhibitors resulted in enhanced anticancer activity against models where MET activation co-occurred with other oncogenic drivers, for example EGFR activating mutations. CONCLUSIONS: Activity of capmatinib in preclinical models is associated with a small number of plausible genomic features. The low fraction of cancer models that respond to capmatinib as a single agent suggests that the implementation of patient selection strategies based on these biomarkers is critical for clinical development. Capmatinib is also a rational combination partner for other kinase inhibitors to combat MET-driven resistance.