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Synthetic lethality has recently emerged as a new approach for the treatment of mutated genes that were previously considered undruggable. Targeting methionine adenosyltransferase 2A (MAT2A) in cancers with deletion of the methylthioadenosine phosphorylase (MTAP) gene leads to synthetic lethality and thus has attracted significant interest in the field of precise anticancer drug development. Herein, we report the discovery of a series of novel MAT2A inhibitors featuring a pyrazolo[3,4-c]quinolin-4-one skeleton based on structure-based drug design. Further optimization led to compound 39, which has a high potency for inhibiting MAT2A and a remarkable selectivity for MTAP-deleted cancer cell lines. Compound 39has a favorable pharmacokinetic profile with high plasma exposure and oral bioavailability, and it exhibits significant efficacy in xenograft MTAP-depleted models. Moreover, 39demonstrates excellent brain exposure with a Kpuuof 0.64 in rats.

Background and objective: The diagnosis and treatment of small bowel diseases (SBDs) has always been a challenge. The purpose of this study was to evaluate the value of double-balloon enteroscopy (DBE) in the diagnosis and treatment of small bowel diseases. Method: The clinical data of 466 patients who underwent double-balloon enteroscopy (DBE) in the Endoscope Center of Gastroenterology Department of the First People's Hospital of Yunnan Province from Jan. 2015 to Dec. 2020 were analysed retrospectively. The factors included age, sex, indications, endoscopic treatment results, pathological results, discharge diagnosis and so on. Results: A total of 370 patients underwent 466 double-balloon enteroscopies, among whom 274 underwent one examination and 96 received two-way examinations (oral and transanal approaches). Abnormalities were detected in 299 cases, with a detection rate of 80.81% (299/370). The common indications were occult gastrointestinal bleeding (OGIB) (30.8%, 114/370) and abdominal pain (28.3%, 105/370). The diagnosis rates were 64.9% and 77.1%, respectively. The common positive findings included nonspecific inflammation/erosion (60 cases), ulcers (34 cases), diverticulum (32 cases), polyps (26 cases) and Crohn's disease (CD) (24 cases). The common tumours were lymphoma(12 cases), adenocarcinoma(11 cases) and stromal tumour(8 cases). Lymphoma was mostly located in the ileum, while stromal tumours and adenocarcinoma were mostly located in the duodenum and jejunum. The main endoscopic intervention measures were haemostasis and polypectomy, including haemostatic clip, argon plasma coagulation (APC), endoscopic mucosal resection (EMR), endoscopic trap resection, endoscopic foreign body extraction and other operations, without serious complications. Conclusion: DBE has a high success rate in the diagnosis and treatment of some SBDs, and it is a safe and effective management method.

As a traditional agricultural country, China has always prioritized agricultural development, and has increasingly focused on green and sustainable agricultural development. Based on the inter-provincial panel data for China from 1997 to 2019, this study divided these data into five periods according to the Five-Year Plan (FYP) of China, measured the agricultural eco-efficiency (AEE) values using the Super-SBM model, and then determined the spatial association network of the inter-provincial AEE of China using the improved gravity model. Finally, social network analysis (SNA) was used to further analyze the evolution process of AEE, and we developed a framework of how multidimensional proximity, which includes geographical, economic, technological, cognitive, and institutional proximity, made an influence on the formation of AEE spatial relation network. The findings indicated that: 1) in 1997–2019, the AEE in China was present in some spatial and temporal differences characteristics at the provincial scale, and we specifically found that national macro-regulation and policy incentives played a positive role in the long-term development of AEE. 2) The spatial correlation of AEE development among provincial regions were becoming closer and exhibits obvious spatial correlation and spillover effects. The evolution of the AEE network has clearly observable trends of hierarchization and aggregation, and the complexity of the correlation network continues to increase and exhibits spatial clustering characteristics that are dense in the east and sparse in the west. The network structure has changed from monocentric radiation to a multicentric network, and network nodes select the more advantageous nodes with which to connect. 3) Finally, the geographical proximity had a significant negative effect; the economic, technological, and institutional proximities were all observed to contribute to the AEE network formation, and cognitive proximity did not significantly influence this network formation.

We report the hydrothermal synthesis of the N-doped carbon-coated NiO nanocrystals (N–C–NiO NCs) with tunable N/C atomic ratios using the nitrogen-containing ionic liquids (ILs) as new carbon precursor, and the N-doped carbon layer composition-dependent performances of N–C–NiO NCs anode for lithium-ion batteries (LIBs). The results indicate that the N-doped carbon coating can significantly enhance the electronic conductivity, effectively avoid the problems of cracking or pulverization of the NiO, and prevent the aggregation of the active materials upon cycling. These properties make the synthesized material a promising anode material for LIBs. The N–C–NiO NCs with the N/C atomic ratio of 21.2% in the N-doped carbon layer show a high specific capacity of ∼710 mAh g–1at a current rate of 0.3 C (very closed to the theoretical capacity of 718 mAh g–1for NiO), a high rate capability (still able to deliver a discharge capacity of ∼430 mAh g–1at a current density of 10 C), and good capacity retention upon cycling (maintains at 710 mAh g–1at least up to the 50th cycle) compared with those of pristine NiO nanoparticles. Moreover, the electrochemical performances of the N–C–NiO NCs depend on the composition (N/C atomic ratios) in the N-doped carbon layer and are enhanced with increasing of the N/C ratios. Our approach offers an effective and convenient technique to improve the specific capacities and rate capabilities of highly insulating electrode materials for batteries and may also provide general and effective approach toward the synthesis of other metal oxides coated with N-doped carbon layer.

Three-dimensional Pd@Pt core−shell nanostructures with controllable shape and composition were synthesized by using a one-step microwave heating method. The nanostructures with the morphology, structure, and composition being easily controlled through adjusting the molar ratio between Pt and Pd precursor were characterized by transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), X-ray powder diffraction (XRD), and energy-dispersive X-ray (EDX) techniques. In addition, the electrocatalytic characteristics of these prepared Pd@Pt electrocatalysts with different Pd/Pt molar ratio for oxygen electro-reduction reaction (ORR) and methanol electro-oxidation reaction (MOR) were systematically investigated by voltammetry. The results show that Pd@Pt electrocatalysts exhibit higher catalytic activity than pure Pd and pure Pt catalysts for both the ORR and MOR, and the highest activity is obtained at the Pd@Pt electrocatalyst with a Pd/Pt molar ratio of 1:3. This result demonstrates that a higher performance of ORR and MOR could be realized at the novel core−shell electrocatalyst while Pt utilization also could be diminished. This method may open a general approach for the shape-controlled synthesis of bimetallic Pt−M nanocatalysts, which can be expected to have promising applications in fuel cells.

Myoglobin (Mb) was immobilized onto the surface of carbon nanotube (CNT) and was characterized by AFM, XPS, UV-Vis, and FTIR spectroscopy. The promotion effect of CNT on direct electron transfer (DET) reaction of Mb was studied. Cyclic voltammetric results showed a pair of well-defined redox peaks, which corresponded to DET of Mb, with the formal potential (E 0) of (-0.343 ± 0.001) V ( vsSCE) in the phosphate buffer solution (PBS, pH 7.0). The electrochemical parameters, such as apparent heterogeneous electron transfer rate constant ( ks) and E0, were determined. The dependence of E0' on solution pH indicated that DET reaction of Mb was coupled with proton transfer. The experimental results also demonstrated that the immobilized Mb retained its bioelectrocatalytic activity toward the reduction of H 2O 2and O 2.

Antifungal azoles are the most widely used antifungal drugs in clinical and agricultural practice. Fungi can mount adaptive responses to azole stress by modifying the transcript levels of many genes, and the responsive mechanisms to azoles are the basis for fungi to develop azole resistance.