Nobiletin regulates the proliferation and migration of ovarian cancer A2780 cells via DPP4 and TXNIP.

Nobiletin is an active compound extracted from citrus fruits. Research has indicated that nobiletin has a potential inhibitory effect on ovarian cancer (OV). However, the mechanism of action remains unclear. The OV A2780 cells were treated using nobiletin, cell viability was examined using a cell counting kit-8 experiment, and cell migration was examined with a wound healing experiment. Nobiletin targets were retrieved from target databases. Differentially expressed genes (DEG) and weighted gene co-expression network analysis (WGCNA) were conducted on GSE26712 (OV). The intersection of the critical genes for nobiletin's action on OV and gene enrichment and immune infiltration analyses were performed. The Cancer Genome Atlas-OV data and molecular docking helped validate the findings. After adding nobiletin, cell viability and migration significantly decreased (P < 0.01). A total of 88 nobiletin targets and 1288 DEG were identified. The intersection genes were enriched inflammatory response and response to hypoxia. The most related module obtained from WGCNA contained 414 genes (correlation coefficient = 0.77, P < 0.01). DPP4 and TXNIP were recognized as the hub genes. The abundance of macrophages M2 and mast cells activated significantly enhanced with increased DPP4 expression (P < 0.05). The binding energy between DPP4/TXNIP and nobiletin was - 7.012/ - 7.184 kcal/mol, forming 5/2 hydrogen bonds. Nobiletin effectively suppresses the viability and migration of OV A2780 cells. In this process, DPP4 and TXNIP are the key target, immune regulation, and oxidative stress playing significant roles.

Local feature acquisition and global context understanding network for very high-resolution land cover classification.

Very high-resolution remote sensing images hold promising applications in ground observation tasks, paving the way for highly competitive solutions using image processing techniques for land cover classification. To address the challenges faced by convolutional neural network (CNNs) in exploring contextual information in remote sensing image land cover classification and the limitations of vision transformer (ViT) series in effectively capturing local details and spatial information, we propose a local feature acquisition and global context understanding network (LFAGCU). Specifically, we design a multidimensional and multichannel convolutional module to construct a local feature extractor aimed at capturing local information and spatial relationships within images. Simultaneously, we introduce a global feature learning module that utilizes multiple sets of multi-head attention mechanisms for modeling global semantic information, abstracting the overall feature representation of remote sensing images. Validation, comparative analyses, and ablation experiments conducted on three different scales of publicly available datasets demonstrate the effectiveness and generalization capability of the LFAGCU method. Results show its effectiveness in locating category attribute information related to remote sensing areas and its exceptional generalization capability. Code is available at https://github.com/lzp-lkd/LFAGCU .

Ganoderma lucidum polysaccharides attenuates pressure-overload-induced pathological cardiac hypertrophy.

Pathological cardiac hypertrophy is an important risk factor for cardiovascular disease. However, drug therapies that can reverse the maladaptive process and restore heart function are limited. Ganoderma lucidum polysaccharides (GLPs) are one of the main active components of G. lucidum (Ganoderma lucidum), and they have various pharmacological effects. GLPs have been used as Chinese medicine prescriptions for clinical treatment. In this study, cardiac hypertrophy was induced by transverse aortic constriction (TAC) in mice. We found that GLPs ameliorate Ang II-induced cardiomyocyte hypertrophy in vitro and attenuate pressure overload-induced cardiac hypertrophy in vivo. Further research indicated that GLPs attenuated the mRNA levels of hypertrophic and fibrotic markers to inhibit cardiac hypertrophy through the PPARγ/PGC-1α pathway. Overall, these results indicate that GLPs inhibit cardiac hypertrophy through downregulating key genes for hypertrophy and fibrosis and attenuate pressure overload-induced pathological cardiac hypertrophy by activating PPARγ. This study provides important theoretical support for the potential of using GLPs to treat pathological myocardial hypertrophy and heart failure.

News headline generation based on improved decoder from transformer.

Most of the news headline generation models that use the sequence-to-sequence model or recurrent network have two shortcomings: the lack of parallel ability of the model and easily repeated generation of words. It is difficult to select the important words in news and reproduce these expressions, resulting in the headline that inaccurately summarizes the news. In this work, we propose a TD-NHG model, which stands for news headline generation based on an improved decoder from the transformer. The TD-NHG uses masked multi-head self-attention to learn the feature information of different representation subspaces of news texts and uses decoding selection strategy of top-k, top-p, and punishment mechanisms (repetition-penalty) in the decoding stage. We conducted a comparative experiment on the LCSTS dataset and CSTS dataset. Rouge-1, Rouge-2, and Rouge-L on the LCSTS dataset and CSTS dataset are 31.28/38.73, 12.68/24.97, and 28.31/37.47, respectively. The experimental results demonstrate that the proposed method can improve the accuracy and diversity of news headlines.

Flexible 3D Porous MXene Foam for High-Performance Lithium-Ion Batteries.

2D transition-metal carbides and nitrides, named MXenes, are promising materials for energy storage, but suffer from aggregation and restacking of the 2D nanosheets, which limits their electrochemical performance. In order to overcome this problem and realize the full potential of MXene nanosheets, a 3D MXene foam with developed porous structure is established via a simple sulfur-template method, which is freestanding, flexible, and highly conductive, and can be directly used as the electrode in lithium-ion batteries. The 3D porous architecture of the MXene foam offers massive active sites to enhance the lithium storage capacity. Moreover, its foam structure facilitates electrolyte infiltration for fast Li+ transfer. As a result, this flexible 3D porous MXene foam exhibits significantly enhanced capacity of 455.5 mAh g-1 at 50 mA g-1 , excellent rate performance (101 mAh g-1 at 18 A g-1 ), and superior ultralong-term cycle stability (220 mAh g-1 at 1 A g-1 after 3500 cycles). This work not only demonstrates the great superiority of the 3D porous MXene foam but also proposes the sulfur-template method for controllable constructing of the 3D foam from 2D nanosheets at a relatively low temperature.

2D MXene nanosheets enable small-sulfur electrodes to be flexible for lithium-sulfur batteries.

Lithium-sulfur batteries are one of the most promising energy storage devices with high energy density, but their practical application is hindered by the serious capacity fading due to the shuttle effect resulting from the migration of polysulifdes during charge-discharge. Using small sulfur molecules (S2-4), in place of conventional cyclo-S8, as cathode materials is an efficient method to fundamentally eradicate the shuttle effect. To satisfy the demands of flexible electronic devices, in this paper, two-dimensional (2D) MXene nanosheets were used as a conductive binder and flexible backbone to combine with the S2-4/carbon composite, fabricating a flexible small-sulfur electrode for lithium-sulfur batteries. The 2D MXene nanosheets with excellent conductivity can not only provide flexibility for the electrode, but also construct a conductive network for fast charge transfer. As a result, the flexible S2-4 electrode exhibits superior electrochemical performance, which has a capacity of 1029.7 mA h g-1 at 0.1 C and maintains 946.7 mA h g-1 after 200 cycles with 91.9% retention. Besides, a capacity of 502.3 mA h g-1 is obtained at 2 C current density. This electrode is promising for flexible lithium-sulfur batteries, and the application of MXene as a conductive binder and flexible backbone in lithium-sulfur batteries offers an effective method to achieve both flexibility and high performance.

Three-Dimensional Carbon Current Collector Promises Small Sulfur Molecule Cathode with High Areal Loading for Lithium-Sulfur Batteries.

With the high energy density of 2600 W h kg-1, lithium-sulfur (Li-S) batteries have been considered as one of the most promising energy storage systems. However, the serious capacity fading resulting from the shuttle effect hinders its commercial application. Encapsulating small S2-4 molecules into the pores of ultramicroporous carbon (UMC) can eliminate the dissolved polysulfides, thus completely inhibiting the shuttle effect. Nevertheless, the sulfur loading of S2-4/UMC is usually not higher than 1 mg cm-2 because of the limited pore volume of UMC, which is a great challenge for small sulfur cathode. In this paper, by applying ultralight 3D melamine formaldehyde-based carbon foam (MFC) as a current collector, we dramatically enhanced the areal sulfur loading of the S2-4 electrode with good electrochemical performances. The 3D skeleton of MFC can hold massive S2-4/UMC composites and act as a conductive network for the fast transfer of electrons and Li+ ions. Furthermore, it can serve as an electrolyte reservoir to make a sufficient contact between S2-4 and electrolyte, enhancing the utilization of S2-4. With the MFC current collector, the S2-4 electrode reaches an areal sulfur loading of 4.2 mg cm-2 and performs a capacity of 839.8 mA h g-1 as well as a capacity retention of 82.5% after 100 cycles. The 3D MFC current collector provides a new insight for the application of Li-S batteries with high areal small sulfur loading and excellent cycle stability.

[Safety evaluation of niuhuang jiedu tablet].

Realgar-containing Niuhuang Jiedu tablet (NHJD) has been applied in clinic for more than 800 years. However, because realgar contains arsenic (As), it has aroused wide concerns and controversies both at home and abroad. Currently, there are two misunderstandings about realgar-containing Chinese patent medicines. First, some people exaggerated realgar's toxicity as that of arsenic. Second, they recommended to remove realgar from traditional Chinese medicine compounds. In this paper, the authors summarized the advance in studies on NHJD, and proposed different opinions: (1) It is inappropriate to take total As as the index in safety evaluation of NHJD. (2) The toxicity of NHJD is dependent on the dose and duration of administration. (3) Realgar is an active ingredient of NHJD, and shall be deeply studied. Classic realgar-containing traditional Chinese medicine prescriptions, such as Niuhuang Jiedu tablet, shall be evaluated with rigorous modern scientific basis, with the aim to guide rational and safe application.

Evaluation of hepatotoxicity potential of cinnabar-containing An-Gong-Niu-Huang Wan, a patent traditional Chinese medicine.

An-Gong-Niu-Huang Wan (AGNH) is a patent traditional Chinese medicine for brain disorders. It contains 10% cinnabar (HgS). Hg is known to produce toxicity to the kidney, brain and liver. Is AGNH safe? Liver is a major organ for drug metabolism, whether the long-term use of AGNH would affect hepatic P450 enzymes is unknown. To address these concerns, mice were given orally cinnabar (300mg/kg), cinnabar-containing AGNH daily for 44days, and liver toxicity was examined and compared with that of methylmercury (MeHg, 2.6mg/kg) and mercuric chloride (HgCl(2), 32mg/kg). Serum aminotransferases were increased by MeHg and HgCl(2) only. Histopathology showed more severe liver damage in MeHg- and HgCl(2)-treated mice than in the cinnabar and AGNH groups. Accumulation of Hg in MeHg- and HgCl(2)-treated mice was 96- and 71-fold higher than controls, respectively, but was only 2-fold after cinnabar and AGNH administration. Expressions of metallothionein-1 and heme oxygenase-1, biomarkers for Hg toxicity, were increased by MeHg and HgCl(2,) but were not altered in cinnabar- and AGNH-treated mice. Expression of hepatic cytochrome P450 genes, such as Cyp1a1, Cyp1b1 and Cyp4a10 was increased only after MeHg and HgCl(2), and the expressions of Cyp3a11and Cyp3a25 were increased by all treatments, indicating the potential Hg-drug interactions after long-term use of cinnabar-containing traditional medicines. Taken together, the results demonstrate that AGNH is much less hepatotoxic than common mercurials, and that the use of total Hg content to evaluate the toxicity of cinnabar-containing traditional Chinese medicines appears to be inappropriate.

Realgar and realgar-containing Liu-Shen-Wan are less acutely toxic than arsenite and arsenate.

ETHNOPHARMACOLOGICAL RELEVANCE: Liu-Shen-Wan (LSW) is a widely-used traditional Chinese medicine containing realgar (As(4)S(4)). AIM OF THE STUDY: Realgar has been included in many traditional medicines, and is often taken as arsenite for risk assessment in realgar-containing traditional remedies. Is realgar toxicologically similar to arsenite? MATERIALS AND METHOD: Mice were orally given LSW (60 and 200mg/kg; 200mg LSW contains 27 mg realgar), realgar (30 mg/kg, equivalent to 21 mg As/kg), and the equivalent As dose as sodium arsenite (NaAsO(2)), or as arsenate (Na(2)HAsO(4)). Acute toxicity and tissue As accumulation were determined 8h later. RESULTS: Arsenite and arsenate increased serum alanine aminotransferase (ALT) levels, indicative of liver injury; blood urea nitrogen (BUN) was also increased by arsenite and arsenate, indicative of nephrotoxicity. No elevations of ALT and BUN were observed in LSW and realgar groups. Histopathology showed more damage in arsenite- and arsenate-treated liver and kidneys, while in realgar- and LSW- treated animals, only mild alterations were seen. Hepatic and renal As contents were dramatically increased to 6200 and 3350ng/g, respectively, after arsenite, but only increased to 260 and 180 ng/g after LSW. The expressions of arsenic-sensitive stress genes, namely metallothionein-1 and heme oxygenase-1, were increased after arsenite or arsenate by 3-10-folds, but were unaltered after LWS and realgar. CONCLUSIONS: Realgar and LSW are much less toxic than arsenite and arenate. The use of total As content to evaluate the safety of realgar-containing traditional medicines is not scientifically sound.

Toxicology evaluation of realgar-containing niu-huang-jie-du pian as compared to arsenicals in cell cultures and in mice.

Niu-Huang-Jie-Du Pian (NHJD) is a widely used traditional Chinese medicine containing realgar (As4S4). Realgar has been included in many traditional medicines, but is often taken as arsenite for risk assessment. To evaluate true risk of realgar and realgar-containing NHJD, their toxicity was compared with common arsenicals. In cultured cells, the LC50 for NHJD (1200 µM) and realgar (2000 µM) was much higher than arsenite(35 µM), arsenic trioxide (280 µM), and arsenate (400 µM). Acute toxicity in mice showed more severe liver and kidney injury after arsenite or arsenate, but was mild after realgar and NHJD, corresponding to cellular and tissue arsenic accumulation. The expressions of arsenic-sensitive stress gene metallothionein-1 were increased 3-7-folds after arsenite or arsenate, but were unaltered after NHJD and realgar. Thus, realgar and NHJD are much less toxic than arsenite and arsenate. The use of total arsenic to evaluate the safety of realgar and realgar-containing NHJD is inappropriate.