Synthesis and electrochemical properties of Sn-SnO2/C nanocomposite

A Sn-Sn02/C nanocomposite was synthesized using the electrospinning method. Thermal analysis was used to determine the content range of Sn and Sn02 in the composite. The composite was characterized by X-ray diffraction, and the particle size and shape in the Sn-SnOiC composite were determined by scanning and transmission electron microscopy. The results show that the Sn-Sn02/C composite takes on a nanofiber morphology, with the diameters of the nanofibers distributed from 50 to 200 nm. The electrOChemical properties of the Sn-SnOiC composite were also investigated. The Sn-SnOiC composite as an electrode material has both higher reversible capacity (887 mAh· g-I). and good cycling performance in lithium-anode ceUs working at room temperature in a 3.0 V to O.Ot V potential window. The Sn-Sn02/C composite could relain a discharge capacity of 546 mAWg aller 30 cycles. The outstanding electrochemical properties of the Sn-SnOiC composite oblained by this method make it possible for Ihis composite to be used as a promising anode material

Incorporating Semantic Similarity with Geographic Correlation for Query-POI Relevance Learning

Point-of-interest (POI) retrieval that searches for relevant destination locations plays a significant role in on-demand ridehailing services. Existing solutions to POI retrieval mainly retrieve and rank POIs based on their semantic similarity scores. Although intuitive, quantifying the relevance of a Query-POI pair by single-field semantic similarity is subject to inherent limitations. In this paper, we propose a novel Query-POI relevance model for effective POI retrieval for ondemand ride-hailing services. Different from existing relevance models, we capture and represent multi-field and local&global semantic features of a Query-POI pair to measure the semantic similarity. Besides, we observe a hidden correlation between origin-destination locations in ride-hailing scenarios, and propose two location embeddings to characterize the specific correlation. By incorporating the geographic correlation with the semantic similarity, our model achieves better performance in POI ranking. Experimental results on two real-world click-through datasets demonstrate the improvements of our model over state-of-the-art methods

Comparative Transcriptome Analysis of Two Sweet Sorghum Genotypes with Different Salt Tolerance Abilities to Reveal the Mechanism of Salt Tolerance

Sweet sorghum is a C4 crop that can be grown for silage forage, fiber, syrup and fuel production. It is generally considered a salt-tolerant plant. However, the salt tolerance ability varies among genotypes, and the mechanism is not well known. To further uncover the salt tolerance mechanism, we performed comparative transcriptome analysis with RNA samples in two sweet sorghum genotypes showing different salt tolerance abilities (salt-tolerant line RIO and salt-sensitive line SN005) upon salt treatment. These response processes mainly focused on secondary metabolism, hormone signaling and stress response. The expression pattern cluster analysis showed that RIO-specific response genes were significantly enriched in the categories related to secondary metabolic pathways. GO enrichment analysis indicated that RIO responded earlier than SN005 in the 2 h after treatment. In addition, we identified more transcription factors (TFs) in RIO than SN005 that were specifically expressed differently in the first 2 h of salt treatment, and the pattern of TF change was obviously different. These results indicate that an early response in secondary metabolism might be essential for salt tolerance in sweet sorghum. In conclusion, we found that an early response, especially in secondary metabolism and hormone signaling, might be essential for salt tolerance in sweet sorghum

Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target

HACE1 is a member of the HECT domain-containing E3 ligases with 909 amino acid residues, containing N-terminal ankyrin-repeats (ANK) and C-terminal HECT domain. Previously, it was shown that HACE1 is inactive in human tumors and plays a crucial role in the initiation, progression, and invasion of malignant tumors. Recent studies indicated that HACE1 might be closely involved in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. HACE1 interacts with its substrates, including Ras-related C3 botulinum toxin substrate 1 (Rac1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumor necrosis factor receptor (TNFR), and optineurin (OPTN), through which participates in several pathophysiological processes, such as oxidative stress, autophagy and inflammation. Therefore, in this review, we elaborately describe the essential substrates of HACE1 and illuminate the pathophysiological processes by which HACE1 is involved in neurodegenerative diseases. We provide a new molecular target for neurodegenerative diseases

A Multilayered Magnetoelectric Transmitter with Suppressed Nonlinearity for Portable VLF Communication

Acoustically actuated magnetoelectric (ME) antenna based on the efficient oscillation of magnetic dipoles has recently been considered as a promising solution for portable very-low-frequency communications. However, the severe nonlinear dynamic behavior in the case of strong-field excitation results in insufficient radiation capability and poor communication performance for a conventional ME antenna. In this work, we propose to suppress the nonlinearity of an ME antenna by neutralizing the spring-hardening effect in amorphous Metglas and the spring-softening effect in piezoelectric ceramics through an ME multilayered transmitter (ME-MLTx) design. With a driving voltage of 50 Vpp at the resonance frequency of 21.2 kHz, a magnetic flux density as high as 108 fT at a distance of 100 m is produced from a single ME-MLTx. In addition, ME-MLTx performs a decreased mechanical quality factor (Q m) less than 40.65, and, thus, a broadened bandwidth of 500 Hz is generated. Finally, a communication link transmitting binary American Standard Code for Information Interchange-coded message is built, which allows for an error-free communication with a distance of 18 m and a data rate of 300 bit/s in the presence of heavy environment noise. The communication distance can be further estimated over 100 m when using a femtotesla-class-inductive magnetic field receiver. The obtained results are believed to bring ME antennas one step closer to being applicable in very-low-frequency communications

Transvaginal ovarian drilling followed by controlled ovarian stimulation from the next day improves ovarian response for the poor responders with polycystic ovary syndrome during IVF treatment: a pilot study

Background: Poor response patients with PCOS who are not susceptible to gonadotropin stimulation are more likely to have canceled cycles or poor clinical outcomes during IVF treatment. However, some limitations exist in the present therapies. In this study, we evaluated the effects of using the transvaginal ovarian drilling (TVOD) followed by controlled ovarian stimulation (COS) from the second day of these poor responders. Methods: During IVF, 7 poor responders with PCOS and 28 PCOS patients (14 normal and 14 high responders) were recruited. All patients received COS with the gonadotropin-releasing hormone antagonist protocol. For the poor responders, after undergoing 10 to 14 days of ovulation induction with no response, the TVOD was applied and then ovarian stimulation was performed from the next day at the same gonadotropin dose. Serum samples during COS and follicular fluid samples from the dominant follicles on the oocyte pick-up (OPU) day in all three groups were collected. Besides, follicular fluid from small follicles (diameter < 1 cm) in the normal and high responders on the OPU day and those in the poor responders on the TVOD day were gathered. Hormonal levels were examined in all samples using immunometric assays. Results: All the poor responders restored ovary response after receiving TVOD. There was no significant difference in the stimulation duration, total gonadotrophin dose used and the clinical outcomes among the three groups. The body mass index, serum and follicular levels of anti-Müllerian hormone (AMH) and testosterone in poor responders were higher than those in the other two groups, and the application of TVOD significantly decreased the levels of AMH and testosterone in both serum and follicular fluid. Conclusions: TVOD followed by ovulation induction from the next day is effective and convenient for poor responders with PCOS. The decline of AMH and testosterone resulted from TVOD may be the main reason resulting in the recovery of ovary sensitivity to gonadotropins. The small sample size is the primary limitation of this study, future studies using a large population cohort and monitoring the long-term outcomes of this strategy will be required. Trial registration: ChiCTR1900023612. Registered 04 June 2019-Retrospectively registered.Medicine, Faculty ofOther UBCNon UBCObstetrics and Gynaecology, Department ofReviewedFacult

Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development

Development of the First Generation of Disulfide-Based Subtype-Selective and Potent Covalent Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors

Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described bis­(4-morpholinyl thiocarbonyl)-disulfide (JX06, <b>16</b>) as the first covalent inhibitor of PDK1. Here, on the basis of the scaffold of <b>16</b>, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analogue, <b>3a</b>, effectively inhibits PDK1 both at the molecular (<i>k</i>_inact/<i>K</i>_i = 4.17 × 10³ M^–1 s^–1) and the cellular level (down to 0.1 μM). In contrast to <b>16</b>, <b>3a</b> is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2–4. <b>3a</b> also significantly alters glucose metabolic pathways in A549 cells by decreasing ECAR and increasing ROS. Moreover, in the xenograft models, <b>3a</b> shows significant antitumor activity with no negative effect to the mice weight. Collectively, these data demonstrate that <b>3a</b> may be an excellent lead compound for the treatment of cancer as a first-generation subtype-selective and covalent PDK1 inhibitor