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Triboelectric nanogenerators (TENGs) are a widely researched type of energy harvester suited to powering mobile micro-electronic devices. In this study, we present a hybrid MAPbIxCl3-x perovskite-based triboelectric nanogenerator (P-TENG) based on the coupling of triboelectric and photoelectric conversion mechanisms for simultaneous vibrating energy and solar energy harvesting. By optimizing the device structure, for the first time, planar TiO2 as electron transport layer (ETL) and ultrathin pentacene as hole transport layer (HTL) are combined together to photoenhance the output of a TENG. Experimental results reveal that P-TENG has achieved the optimal photoinduced enhancement due to the most effective charge separation that relies on the joint of HTL and ETL. As a result, the optimized P-TENG with ~ 0.7 cm2 effective area, the open-circuit voltage (Voc), short-circuit current (Isc) and the maximum transfer charge amount (Qsc) are increased by 55.7%, 50.8% and 58.2% upon illumination, respectively. Besides, the P-TENG shows fast response on both the full-spectrum simulated sunlight and monochromatic light extending from ultraviolet to entire visible region which enhances the potential application in photodetection. Our work presents a route to designing high-performance P-TENG via interfacial engineering to further boost the output ability of this photoelectric hybrid TENG.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg·kg −1 ·d −1 , ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH.

The frequent occurrence of extreme drought events in Guangxi has caused huge losses to human beings and economy in the region for many years. For fine identification of drought evolution characteristics, this study adopted the objective identification method of regional extreme events (OITREE) to carry out the comprehensive feature identification involving multidimensional elements such as intensity, duration and area of meteorological drought events based on the daily standardized precipitation evapotranspiration index (SPEI) data of Guangxi from 1979 to 2018a. By comparing the evolution characteristics of drought elements identified by grid SPEI statistical analysis and OITREE, a comprehensive analysis framework for drought characteristics of multidimensional factor's measurement is formed in this study. Specifically, the grid analysis is more convenient to identify single point drought characteristics, and the OITREE method is better at describing the overall spatiotemporal evolution of drought events. The study found that flash droughts and seasonal droughts occurred alternately and were superimposed concurrently in Guangxi, and the multidimensional spatial and temporal characteristics of these two types of droughts were significantly different. In concrete terms, the average annual frequency of flash drought events in Guangxi was 2.0-3.8, the average annual duration varied from 20 to 60 d, and the concentration point of drought events had a region-wide dispersion; while the average annual frequency of seasonal drought events in Guangxi was 0.82-1.65, the average annual duration varied from 40 to 105 d, and the concentration point of drought events had a local concentration. Furthermore, for the flash drought, seasonal drought and total drought in Guangxi, the three-dimension clustering method was introduced to realize the comprehensive intensity spatial heterogeneity clustering partition and temporal heterogeneity clustering mapping of meteorological drought in Guangxi. The research results can provide important scientific support for promoting the operational risk assessment and regulation of regional drought disasters and forecasting and warning.

Background Carpal tunnel syndrome (CTS) is the most common entrapment symptom in the peripheral nerves. High-frequency ultrasound (HFUS) is widely used in the diagnosis of CTS. Virtual Touch Tissue Imaging and Quantification (VTIQ), which provides more information about the hardness of organization, is used to diagnose CTS. However, the data of diagnostic value of them in various degrees of CTS are limited. Whether the combination of HFUS and VTIQ can improve the diagnostic efficiency also remains unknown. The study aimed to explore the diagnostic value of HFUS and VTIQ in various degrees of CTS and whether combination of HFUS and VTIQ could improve the diagnostic efficiency of CTS. Methods A collection and analysis of 133 CTS patients and 35 volunteers from January 2016 to January 2019 were performed. We compared the clinical characteristics, cross-sectional area (CSA) value and shear wave velocity SWV mean value of CTS group with volunteer group. Results The CSA value and SWV mean value of CTS cohort were significantly higher than volunteer group (10.79 ± 2.88 vs. 8.06 ± 1.39, p  < 0.001, 4.36 ± 0.95 vs. 3.38 ± 1.09, p <  0.001, respectively). The area under the curve (AUC) of receiver operating characteristic (ROC) curve of CSA value and SWV mean value were 0.794 and 0.757, respectively. Hierarchical analysis of CSA value and SWV mean value showed that the AUC in the moderate and severe CTS group were higher than in mild CTS group. Furthermore, the CSA value combined with SWV mean value used to diagnose mild CTS was 0.758, which was higher than that of single CSA value or single SWV mean value. Conclusions Both HFUS and VTIQ technology were feasible to evaluate CTS. HFUS was suitable for use in diagnosis of moderate and severe CTS. For mild CTS, combination of HFUS and VTIQ was relevant to improve the diagnostic efficiency of CTS.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Here we report that a p300/CBP inhibitor, A-485, could overcome resistance to idelalisib in MCL cells in vitro and in vivo. A-485 was discovered in a combinational drug screening from an epigenetic compound library containing 45 small molecule modulators. We found that A-485, the highly selective catalytic inhibitor of p300 and CBP, was the most potent compound that enhanced the sensitivity of MCL cell line Z-138 to idelalisib. Combination of A-485 and idelalisib remarkably decreased the viability of three MCL cell lines tested. Co-treatment with A-485 and idelalisib in Maver-1 and Z-138 MCL cell xenograft mice for 3 weeks dramatically suppressed the tumor growth by reversing the unsustained inhibition in PI3K downstream signaling. We further demonstrated that p300/CBP inhibition decreased histone acetylation at RTKs gene promoters and reduced transcriptional upregulation of RTKs, thereby inhibiting the downstream persistent activation of MAPK/ERK signaling, which also contributed to the pathogenesis of MCL. Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) is an inhibitor of GAPDH with K i  = 0.5 μM. PGG blocks GAPDH activity by a reversible and NAD + and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD + and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.

The cAMP-responsive element binding protein (CREB) binding protein (CBP) and adenoviral E1A-binding protein (P300) are two closely related multifunctional transcriptional coactivators. Both proteins contain a bromodomain (BrD) adjacent to the histone acetyl transferase (HAT) catalytic domain, which serves as a promising drug target for cancers and immune system disorders. Several potent and selective small-molecule inhibitors targeting CBP BrD have been reported, but thus far small-molecule inhibitors targeting BrD outside of the BrD and extraterminal domain (BET) family are especially lacking. Here, we established and optimized a TR-FRET-based high-throughput screening platform for the CBP BrD and acetylated H4 peptide. Through an HTS assay against an in-house chemical library containing 20 000 compounds, compound DC_CP20 was discovered as a novel CBP BrD inhibitor with an IC 50 value of 744.3 nM. This compound bound to CBP BrD with a K D value of 4.01 μM in the surface plasmon resonance assay. Molecular modeling revealed that DC_CP20 occupied the Kac-binding region firmly through hydrogen bonding with the conserved residue N1168. At the celluslar level, DC_CP20 dose-dependently inhibited the proliferation of human leukemia MV4-11 cells with an IC 50 value of 19.2 μM and markedly downregulated the expression of the c-Myc in the cells. Taken together, the discovery of CBP BrD inhibitor DC_CP20 provides a novel chemical scaffold for further medicinal chemistry optimization and a potential chemical probe for CBP-related biological function research. In addition, this inhibitor may serve as a promising therapeutic strategy for MLL leukemia by targeting CBP BrD protein.

Duck breed Longshengcui ( Linnaeus, 1758 breed Longshengcui, LSC) is one of the famous native breed of the Guangxi Zhuang Nationality Autonomous Region in China. In this study, we report the complete mitochondrial genome of LSC. The mitogenome (GenBank accession no. MZ895120) has 16,602 bp in length and consisted of the well-known 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and the control region. The phylogenetic analysis showed that LSC and Zhijiang duck have highly similar genetic relationship. These results are helpful for the conservation of genetic resources and phylogeny of this species.

Background As a novel marker of insulin resistance, the ratio of triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) has been recently reported to be related to the occurrence of coronary artery diseases. However, no research has been conducted to probe whether the TG/HDL-C ratio is associated with the occurrence of coronary microvascular disease (CMVD). Aim This study investigates the association between the TG/HDL-C ratio and the occurrence of CMVD. Methods This study included 175 patients diagnosed with CMVD in the Department of Cardiology of our hospital from October 2017 to October 2021 as the study group and 175 patients with no chest pain, no history of cardiovascular disease and drug use, and negative results of exercise treadmill testing as the non-CMVD group. The clinical data of the two groups were compared. In addition, the risk factors of CMVD were analyzed with logistic regression, and the efficacy of independent risk factors in predicting CMVD was analyzed with a receiver operating characteristic (ROC) curve. Results Compared with those in the non-CMVD group, the proportion of females, the incidence of hypertension and type 2 diabetes, the level of platelet count, TG, and C-reactive protein, and the ratio of TG/HDL-C were increased in the CMVD group, accompanied by decreased levels of albumin and HDL-C ( P  < 0.05). Logistic regression results revealed C-reactive protein (the area under the ROC curve [AUC] value: 0.754; 95% confidence interval [CI]: 0.681–0.827), sex (the AUC value: 0.651; 95%CI: 0.571–0.730), albumin (the AUC value: 0.722; 95%CI: 0.649–0.794), and TG/HDL-C ratio (the AUC value: 0.789; 95%CI: 0.718–0.859) as the independent risk factors of CMVD. Conclusion The TG/HDL-C ratio is an independent risk factor for the occurrence of CMVD.

Landslides distribute extensively in Rongxian county, the southeast of Guangxi province, China and pose great threats to this county. At present, hazard management strategy is facing an unprecedented challenge due to lack of a landslide susceptibility map. Therefore, the purpose of this paper was to construct a landslide susceptibility map by adopting three widely used models based on an integrated understanding of landslide’s characteristics. These models include a semi-quantitative method (SQM), information value model (IVM) and logistical regression model (LRM).The primary results show that (1) the county is classified into four susceptive regions, named as very low, low, moderate and high, which covered an area of 13.43%, 32.40%, 31.19% and 22.99% in SQM, 0.86%, 26.82%, 44.11%, and 28.21% in IVM, 9.88%, 17.73%, 46.36% and 26.03% in LRM; (2) landslides are likely to occur within the areas characterized by following obvious aspects: high intensity of human activities, slope angles of 25°~35°, the thickness of weathered soil is larger than 15 m; the lithology is granite, shale and mud rock; (3) the area under the curve of SQM, IVM and LRM is 0.7151, 0.7688 and 0.7362 respectively, and the corresponding success rate is 71.51%, 76.88% and 73.62%. It is concluded that these three models are acceptable because they have an effective capability of susceptibility assessment and can achieve an expected accuracy. In addition, the susceptibility outcome obtained from IVM provides a slightly higher quality than that from SQM, LRM.