Mechanisms of Heavy Metal Cadmium (Cd)-Induced Malignancy.

The environmental pollution of cadmium is worsening, and its significant carcinogenic effects on humans have been confirmed. Cadmium can induce cancer through various signaling pathways, including the ERK/JNK/p38MAPK, PI3K/AKT/mTOR, NF-κB, and Wnt. It can also cause cancer by directly damaging DNA and inhibiting DNA repair systems, or through epigenetic mechanisms such as abnormal DNA methylation, LncRNA, and microRNA. However, the detailed mechanisms of Cd-induced cancer are still not fully understood and require further investigation.

Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability.

Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, it was found that the ABZ-BA group had 2.7-fold greater than that of Albenda after 1 month of oral administration. The relative bioavailability of ABZ-BA is significantly better than ABZ due to the transformation of the physical state from a crystalline state to an amorphous state. Furthermore, sodium-dependent bile acid transporter (ASBT) expressed in the apical small intestine has a synergistic effect through the effective transport of bile acids. Therefore, we concluded that the NC formulation could potentially be developed to improve anti-AE drug therapy.

Optimization of supercritical-CO2 extraction and pharmacokinetics in SD rats of alkaloids form Sophora moorcroftiana seed.

The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box-Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 µg. The linear range of UPLC-HR-ESI-MS is 0.78-200.00 ng/ml, R2 > 0.99, and the sample recovery is 99-113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications.

Ultra-low friction and patterning on atomically thin MoS2via electronic tight-binding.

Atomically thin two-dimensional molybdenum disulfide (MoS2) is well known for its excellent lubrication characteristics and is usually used as a solid lubricant in diverse micro/nanoelectromechanical systems (MEMS/NEMS). The friction on atomically thin MoS2 deposited on a SiO2/Si substrate is reduced almost five times to achieve an ultra-low friction state (coefficient of friction nearly 0.0045) by rubbing the surface with an AFM tip under the electric field. The electric field leads to a shift and accumulation of charges at the interface between MoS2 and the SiO2/Si substrate. Then, electronic tight-binding with high interfacial bonding strength is experimentally found by the charges transferring during the rubbing process. The ultra-low friction state of atomically thin MoS2 could attribute to the electronic tight-binding between MoS2 and the SiO2/Si substrate, which suppresses the atomic-scale deformation and limits the local pinning capability of MoS2. The ultra-low friction state on atomically thin MoS2 is patterned further by controllably regulating position, time, and electric field during the rubbing process. This approach can provide an additional channel to achieve ultra-low friction on MoS2 related two-dimensional materials with semiconductor properties. The nanopatterning of ultra-low friction could promote and expand engineering applications of MoS2 as lubricants in various MEMS/NEMS with nano-scale components.

Impact of the Surface and Microstructure on the Lubricative Properties of MoS2 Aging under Different Environments.

Molybdenum disulfide (MoS2) with a hydrophobic property and layered structure possesses an excellent lubricative property and has been widely used as a lubricant in various areas, including satellites, aircraft, and new energy vehicles. Aging is a ubiquitous phenomenon in MoS2 and plays a key role in its tribological application for shortening its service life. The effect of the surface and microstructure on the lubricative properties of MoS2 aging under different environments, including deionized water (DI water), ultraviolet/ozone (UV/Ozone), and high-temperature, was investigated. First, the lubrication of MoS2 transiently degrades because of physical adsorption and recovers after mechanical removal. The lubrication of MoS2 also degrades slightly when its surface becomes hydrophilic, thereby enhancing the adhesion energy due to atomic oxygen interaction under UV/Ozone exposure. Second, the lubrication of MoS2 degrades irreversibly because of the formation of stripes with the destroyed structures under accelerated aging. The lubrication of MoS2 further degrades with the formation of small triangular pits under high-temperature annealing. Finally, the lubrication of MoS2 deteriorates due to the destroyed structure and complete oxidation. The severe aging of MoS2 is accompanied with large triangular pits due to anisotropic oxidation etching of MoS2. The lubrication failure of MoS2 was determined on the basis of structural defect formation and surface property degradation induced by the extent of oxygen diffusion. The enhanced out-of-plane deformation due to the reduced out-of-plane stiffness and the increased energy barriers of defects are fundamentally responsible for the lubrication degradation of MoS2 at the atomic scale. These findings can provide new insights into the atomic-scale mechanism underlying the lubrication failure of MoS2 and pave the way for the realization of MoS2-based lubrication application under various environments.

Simulation of the flow field and the chemical reaction coupling of selective catalytic reduction (SCR) system using an orthogonal experiment.

It is difficult to simulate both the flow field and the chemical reaction using, respectively, the flow state and kinetics calculations and actually reflect the influence of the gas flow state on the chemical change in a selective catalytic reduction (SCR) system. In this study, the flow field and the chemical reaction were therefore coupled to simulate a full Cu-Zeolite SCR system and the boundary conditions of the simulation were set by a relevant diesel engine bench test which included the exhaust temperature, the mass flow, and the exhaust pressure. Then, the influence of the gas flow state on the NOx conversion efficiency was investigated. Specifically, an orthogonal experimental design was used to study the influence of the injection parameters (position, angle, and speed) on the NH3 distribution by establishing the NH3 uniformity coefficient γ at the SCR catalyst capture surface in the flow field simulation. Then, the velocity capture surface of the SCR catalyst front section was sliced into coupled data transfer interfaces to study the effects of exhaust temperature, ammonia to NOx ratio (ANR), and the NO2/NOx on the NOx conversion efficiency. This was used as guidelines to optimize the SCR system control strategy. The results showed that a 1150 mm injection position, a 45°injection angle, and a 23 m/s injection velocity provided the most uniform NH3 distribution on the SCR catalyst capture surface. For constant injection parameters, the NOx conversion efficiency was the highest when the exhaust temperature was 200°C-400°C, the ANR was 1.1, and NO2/NOx was 0.5.

An ultra-low frictional interface combining FDTS SAMs with molybdenum disulfide.

Interfacial friction is of crucial importance to ensure the friction-reducing and anti-wear properties of mechanical microstructures in micro/nanoelectromechanical systems (MEMS/NEMS). An ultra-low frictional interface combining hydrophobic 1H,1H,2H,2H-perfluorodecyltrichlorosilane (FDTS) self-assembled monolayers (SAMs) coated on an AFM tip with mechanically exfoliated molybdenum disulfide (MoS2) nanosheets deposited on a planar Si/SiO2 substrate was achieved. The FDTS SAMs/MoS2 interface between the FDTS SAMs and the MoS2 nanosheets exhibits an ultra-low friction force that is independent of the relative humidity. The incommensurate contact with ultra-low energy dissipation between FDTS and MoS2 nanosheets and hydrophobic surface properties lead to this ultra-low frictional FDTS SAMs/MoS2 interface. Also, the MoS2 nanosheets have a high elastic modulus, which gives them a smaller contact area than the FDTS SAMs and contributes to the low friction. The excellent hydrophobic properties of both the FDTS SAMs and MoS2 enable them to be unaffected by the relative humidity by preventing the capillary interaction. This study paves the way for extensive applications in reducing the friction of nanoscale contact interfaces.