Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells

Doxorubicin (DOX), an anthracycline antibiotic, is one of the most active anticancer chemotherapeutic agents. The clinical use of DOX, however, is limited by the dose-dependant P-glycoprotein (P-gp)-mediated resistance. Herein, a 3′-azido analogue of DOX (ADOX) was prepared from daunorubicin (DNR). ADOX exhibited potent antitumor activities in drug-sensitive (MCF-7 and K562) and drug-resistant cell lines (MCF-7/DNR, K562/DOX), respectively. The drug resistance index (DRI) values of ADOX were much lower than that of DOX. The cytotoxicity experiments of ADOX or DOX against K562/DOX, with or without P-gp inhibitor, indicated that ADOX circumvents resistance by abolishing the P-gp recognition. This conclusion was further supported by drug influx/efflux flow cytometry experiments, as well as by molecular docking of ADOX to P-gp. In vivo animal tests, ADOX exhibited higher activity and less toxicity than DOX. The current data warranted ADOX for additional pre-clinical evaluations for new drug development

Giant polarization in super-tetragonal ferroelectric thin films through interphase strain

Strain engineering has emerged as a powerful tool to enhance the performance of known functional materials. Here we demonstrate a general and practical method to obtain super-tetragonality and giant polarization using interphase strain. We use this method to create an out-of-plane–to–in-plane lattice parameter ratio of 1.238 in epitaxial composite thin films of tetragonal lead titanate (PbTiO3), compared to 1.065 in bulk. These thin films with super-tetragonal structure possess a giant remanent polarization, 236.3 microcoulombs per square centimeter, which is almost twice the value of known ferroelectrics. The super-tetragonal phase is stable up to 725°C, compared to the bulk transition temperature of 490°C. The interphase-strain approach could enhance the physical properties of other functional materials.PostprintPeer reviewe

Organic acids enhance the uptake of lead by wheat roots

Abstract The uptake and bioavailability of lead (Pb) in soil-plant systems remain poorly understood. This study indicates that acetic and malic acids enhance the uptake of Pb by wheat (Triticum aestivum L.) roots under hydroponic conditions. The net concentration-dependent uptake influx of Pb in the presence and absence of organic acids was characterized by Michaelis-Menten type nonsaturating kinetic curves that could be resolved into linear and saturable components. Fitted maximum uptake rates (V max ) of the Michaelis-Menton saturable component in the presence of acetic and malic acids were, respectively, 2.45 and 1.63 times those of the control, while the Michaelis-Menten K m values of 5.5, 3.7 and 2.2 lM, respectively, remained unchanged. Enhanced Pb uptake by organic acids was partially mediated by Ca 2+ and K + channels, and also depended upon the physiological function of the plasma membrane P-type ATPase. Uptake may have been further enhanced by an effectively thinner unstirred layer of Pb adjacent to the roots, leading to more rapid diffusion towards roots. X-ray absorption spectroscopic studies provided evidence that the coordination environment of Pb in wheat roots was similar to that of Pb(CH 3 COO) 2 Á3H 2 O in that one Pb atom was coordinated to four oxygen atoms via the carboxylate group. Keywords Ca 2+ and K + channels Á Organic acids Á P-type ATPase Á Uptake of lead (Pb) Á Wheat (Triticum aestivum L.) Á X-ray absorption spectroscop

Ferroelectricity in layered bismuth oxide down to 1 nanometer

Atomic-scale ferroelectrics are of great interest for high-density electronics, particularly field-effect transistors, low-power logic, and nonvolatile memories. We devised a film with a layered structure of bismuth oxide that can stabilize the ferroelectric state down to 1 nanometer through samarium bondage. This film can be grown on a variety of substrates with a cost-effective chemical solution deposition. We observed a standard ferroelectric hysteresis loop down to a thickness of ~1 nanometer. The thin films with thicknesses that range from 1 to 4.56 nanometers possess a relatively large remanent polarization from 17 to 50 microcoulombs per square centimeter. We verified the structure with first-principles calculations, which also pointed to the material being a lone pair-driven ferroelectric material. The structure design of the ultrathin ferroelectric films has great potential for the manufacturing of atomic-scale electronic devices.This work was supported by the National Key Research and Development Program of China (2018YFA0703700, 2017YFE0119700, and 2020YFA0406202), the National Natural Science Foundation of China (21801013, 51774034, 51961135107, 62104140, 12175235, 22090042, 12074016, 11704041, and 12274009), the Fundamental Research Funds for the Central Universities (FRF-IDRY-19-007 and FRF-TP-19-055A2Z), the National Program for Support of Top-notch Young Professionals, the Young Elite Scientists Sponsorship Program by CAST (2019-2021QNRC), and Lingang Laboratory Open Research Fund (grant LG-QS-202202-11). Use of the Beijing Synchrotron Radiation Facility (1W1A beamlines, China) of the Chinese Academy of Sciences is acknowledged. Y.-W.F. acknowledges the support of Masaki Azuma’s group during his stay at the Tokyo Institute of Technology. Y.L. acknowledges the support of the Beijing Innovation Team Building Program (grant no. IDHT20190503), the Beijing Natural Science Foundation (Z210016), the Research and Development Project from the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering (2022SX-TD001), and the General Program of Science and Technology Development Project of Beijing Municipal Education Commission (KM202110005003).Peer reviewe

Investigation of cracks in GaN films grown by combined hydride and metal organic vapor-phase epitaxial method

Cracks appeared in GaN epitaxial layers which were grown by a novel method combining metal organic vapor-phase epitaxy (MOCVD) and hydride vapor-phase epitaxy (HVPE) in one chamber. The origin of cracks in a 22-μm thick GaN film was fully investigated by high-resolution X-ray diffraction (XRD), micro-Raman spectra, and scanning electron microscopy (SEM). Many cracks under the surface were first observed by SEM after etching for 10 min. By investigating the cross section of the sample with high-resolution micro-Raman spectra, the distribution of the stress along the depth was determined. From the interface of the film/substrate to the top surface of the film, several turnings were found. A large compressive stress existed at the interface. The stress went down as the detecting area was moved up from the interface to the overlayer, and it was maintained at a large value for a long depth area. Then it went down again, and it finally increased near the top surface. The cross-section of the film was observed after cleaving and etching for 2 min. It was found that the crystal quality of the healed part was nearly the same as the uncracked region. This indicated that cracking occurred in the growth, when the tensile stress accumulated and reached the critical value. Moreover, the cracks would heal because of high lateral growth rate

A Military Object Detection Model of UAV Reconnaissance Image and Feature Visualization

Military object detection from Unmanned Aerial Vehicle (UAV) reconnaissance images faces challenges, including lack of image data, images with poor quality, and small objects. In this work, we simulate UAV low-altitude reconnaissance and construct the UAV reconnaissance image tank database UAVT-3. Then, we improve YOLOv5 and propose UAVT-YOLOv5 for object detection of UAV images. First, data augmentation of blurred images is introduced to improve the accuracy of fog and motion-blurred images. Secondly, a large-scale feature map together with multi-scale feedback is added to improve the recognition ability of small objects. Thirdly, we optimize the loss function by increasing the loss penalty of small objects and classes with fewer samples. Finally, the anchor boxes are optimized by clustering the ground truth object box of UAVT-3. The feature visualization technique Class Action Mapping (CAM) is introduced to explore the mechanisms of the proposed model. The experimental results of the improved model evaluated on UAVT-3 show that the mAP reaches 99.2%, an increase of 2.1% compared with YOLOv5, the detection speed is 40 frames per second, and data augmentation of blurred images yields an mAP increase of 20.4% and 26.6% for fog and motion blur images detection. The class action maps show the discriminant region of the tanks is the turret for UAVT-YOLOv5

A Military Object Detection Model of UAV Reconnaissance Image and Feature Visualization

Military object detection from Unmanned Aerial Vehicle (UAV) reconnaissance images faces challenges, including lack of image data, images with poor quality, and small objects. In this work, we simulate UAV low-altitude reconnaissance and construct the UAV reconnaissance image tank database UAVT-3. Then, we improve YOLOv5 and propose UAVT-YOLOv5 for object detection of UAV images. First, data augmentation of blurred images is introduced to improve the accuracy of fog and motion-blurred images. Secondly, a large-scale feature map together with multi-scale feedback is added to improve the recognition ability of small objects. Thirdly, we optimize the loss function by increasing the loss penalty of small objects and classes with fewer samples. Finally, the anchor boxes are optimized by clustering the ground truth object box of UAVT-3. The feature visualization technique Class Action Mapping (CAM) is introduced to explore the mechanisms of the proposed model. The experimental results of the improved model evaluated on UAVT-3 show that the mAP reaches 99.2%, an increase of 2.1% compared with YOLOv5, the detection speed is 40 frames per second, and data augmentation of blurred images yields an mAP increase of 20.4% and 26.6% for fog and motion blur images detection. The class action maps show the discriminant region of the tanks is the turret for UAVT-YOLOv5

The hippocampus underlies the association between self-esteem and physical health

Abstract Self-esteem refers to the extent to which we feel positive or negative about ourselves, and reflects an individual’s subjective evaluation of personal worth and attitudes about the self. As one kind of positive psychosocial resources, high self-esteem has been found to buffer the effects of stress on physical health. However, little is known about the possible neural basis underlying the association between physical health and self-esteem. In the present study, we investigated whether the hippocampus served as a neuroanatomical basis for the association between self-esteem and physical health in a large population of healthy young adults. We examined self-esteem and self-reported physical health with the Rosenberg Self Esteem Scale (RSES) and the Chinese Constitution Questionnaire (CCQ) respectively, and gray matter volume of the hippocampus was measured using magnetic resonance imaging. As expected, we found that individuals with higher levels of self-esteem had better self-reported physical health. Importantly, the mediation analysis showed that the gray matter volume of the hippocampus mediated the link between self-esteem and physical health, suggesting its critical role in the neural circuitry through which self-esteem is related to physical health