Search Results (22)

During a prolonged domestication and environmental selection, Brassica rapa has formed diverse morphological types during a cultivation process of up to 8000 years, such as root-type turnips (Brassica rapa var. rapa), leaf-type Chinese cabbage (Brassica rapa var. pekinensis), oil-type rapeseed (Brassica rapa L.), and other rich types. China is one of the origins of Brassica rapa L., which is spread all over the east, west, south, and north of China. Studying its origin and evolution holds significant importance for unraveling the cultivation history of Chinese oilseed crops, intraspecific evolutionary relationships, and the utilization value of genetic resources. This article summarizes the cultivation history, evolution, classification research progress, and germplasm resource diversity of Brassica rapa var. oleifera in China. Combining karyotype analysis, genomic information, and wild relatives of Brassica rapa var. oleifera discovered on the Qinghai–Tibet Plateau, it is proposed that Brassica rapa var. oleifera has the characteristic of polycentric origin, and Gansu Province in China is one of the earliest regions for its cultivation. Brassica rapa var. oleifera, originating from the Mediterranean region, was diffused to the East Asian continent through two independent transmission paths (one via the Turkish Plateau and the other via Central Asia and Siberia). Analyzing the genetic diversity characteristics and evolutionary trajectories of these two transmission paths lays a foundation for clarifying the origin and evolutionary process of Brassica rapa var. oleifera and accelerating the breeding of Brassica rapa var. oleifera in China. Despite existing research on the origin of Brassica rapa L., the domestication process of this species remains unresolved. Future studies will employ whole-genome resequencing to address this fundamental question. Full article

Natural products, characterized by their structural novelty, multi-target capabilities, and favorable toxicity profiles, represent a prominent reservoir for the discovery of innovative anticancer therapeutics. In the current investigation, we identified ajuforrestin A, a diterpenoid compound extracted from Ajuga lupulina Maxim, as a potent agent against lung cancer. In vitro, this compound markedly curtailed the proliferation of A549 cells. Mechanistic explorations revealed that ajuforrestin A could arrest A549 cells in the G0/G1 phase of the cell cycle, provoke apoptosis in cancer cells, and impede their migration by modulating the STAT3 and FAK signaling cascades. Angiogenesis is indispensable for tumor formation, progression, and metastatic dissemination. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are established as crucial mediators in tumor neovascularization, a process fundamental to both the expansion of tumor cells and the development of new blood vessels within the tumor milieu. Through the combined application of a Tg(fli1:EGFP) zebrafish model and SPR experimentation, we furnished strong evidence for the ability of ajuforrestin A to obstruct tumor angiogenesis via selective engagement with VEGFR-2. Finally, a zebrafish xenograft tumor model demonstrated that ajuforrestin A could effectively restrain tumor growth and metastasis in vivo. Ajuforrestin A therefore shows considerable promise as a lead compound for the future development of therapies against non-small cell lung cancer (NSCLC). Full article

Cancer treatment remains a formidable challenge globally. Natural products, particularly natural alkaloids, have emerged as significant resources for the development of novel anti-tumor drugs due to their structural diversity and unique biological activities. Our team previously isolated an alkaloid, 6-hydroxymethyldihydrochelerythrine (6-HMDN), from Zanthoxylum ailanthoides. Subsequent in vitro and in vivo activity screenings, utilizing cell-based assays and a zebrafish xenograft model, revealed that 6-HMDN significantly inhibited the proliferation of HepG2 and MCF7 cells and effectively suppressed HepG2 cell migration. Mechanistic studies indicated that 6-HMDN induced tumor cell apoptosis by modulating the Bcl-2/Bax protein balance and activating the caspase cascade. Furthermore, 6-HMDN augmented intracellular reactive oxygen species (ROS) levels, thereby promoting ferroptosis, as evidenced by lipid ROS accumulation and glutathione (GSH) depletion. Additionally, 6-HMDN attenuated focal adhesion kinase (FAK) phosphorylation, leading to the inhibition of tumor cell migration. In vivo experiments further substantiated the capacity of 6-HMDN to effectively suppress tumor proliferation and metastasis. These findings demonstrate that 6-HMDN exhibits potent anti-tumor activity, exerting its effects through multiple mechanisms involving the regulation of apoptosis, ferroptosis, and the FAK signaling pathway. Therefore, 6-HMDN may be considered a promising candidate for anti-tumor drug development. Full article

This study explored the potential of saponins from Korean Red Ginseng to target the PINK1/Parkin mitophagy pathway, aiming to enhance insulin sensitivity in hepatocytes—a key factor in metabolic disorders like metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. Results from both in vitro and in vivo experiments showed increased expression of PINK1 and Parkin, activating mitophagy and reducing oxidative stress through reduction in mitochondrial and total reactive oxygen species. Additionally, improvements in insulin signaling were observed, including the upregulation of phosphorylated IRS and AKT, and downregulation of gluconeogenic enzymes, underscoring the saponins’ efficacy in boosting insulin sensitivity. The findings highlighted Korean Red Ginseng-derived saponins as potential treatments for insulin resistance and related metabolic conditions. Full article

In situ depot gel is a type of polymeric long-acting injectable (pLAI) drug delivery system; compared to microsphere technology, its preparation process is simpler and more conducive to industrialization. To ensure the chemical stability of peptide ACTY116, we avoided the use of harsh conditions such as high temperatures, high shear mixing, or homogenization; maintaining a water-free and oxygen-free environment was also critical to prevent hydrolysis and oxidation. Molecular dynamics (MDs) simulations were employed to assess the stability mechanism between ACTY116 and the pLAI system. The initial structure of ACTY116 with an alpha helix conformation was constructed using SYBYL-X, and the copolymer PLGA was generated by AMBER 16; results showed that PLGA-based in situ depot gel improved conformational stability of ACTY116 through hydrogen bonds formed between peptide ACTY116 and the components of the pLAI formulation, while PLGA (Poly(DL-lactide-co-glycolide)) also created steric hindrance and shielding effects to prevent conformational changes. As a result, the chemical and conformational stability and in vivo long-acting characteristics of ACTY116 ensure its enhanced efficacy. In summary, we successfully achieved our objective of developing a highly stable peptide-loaded long-acting injectable (LAI) in situ depot gel formulation that is stable for at least 3 months under harsh conditions (40 °C, above body temperature), elucidating the underlying stabilisation mechanism, and the high stability of the ACTY116 pLAI formulation creates favourable conditions for its in vivo pharmacological activity lasting for weeks or even months. Full article

Mevalonate kinase (MevK) is an important enzyme in the mevalonate pathway that catalyzes the phosphorylation of mevalonate into phosphomevalonate and is involved in juvenile hormone biosynthesis. Herein, we present a structure model of MevK from the red flour beetle Tribolium castaneum (TcMevK), which adopts a compact α/β conformation that can be divided into two parts: an N-terminal domain and a C-terminal domain. A narrow, deep cavity accommodating the substrate and cofactor was observed at the junction between the two domains of TcMevK. Computational simulation combined with site-directed mutagenesis and biochemical analyses allowed us to define the binding mode of TcMevK to cofactors and substrates. Moreover, TcMevK showed optimal enzyme activity at pH 8.0 and an optimal temperature of 40 °C for mevalonate as the substrate. The expression profiles and RNA interference of TcMevK indicated its critical role in controlling juvenile hormone biosynthesis, as well as its participation in the production of other terpenoids in T. castaneum. These findings improve our understanding of the structural and biochemical features of insect Mevk and provide a structural basis for the design of MevK inhibitors. Full article

Zaluzanin C (ZC), a sesquiterpene lactone isolated from Laurus nobilis L., has been reported to have anti-inflammatory and antioxidant effects. However, the mechanistic role of ZC in its protective effects in Kupffer cells and hepatocytes has not been elucidated. The purpose of this study was to elucidate the efficacy and mechanism of action of ZC in Kupffer cells and hepatocytes. ZC inhibited LPS-induced mitochondrial ROS (mtROS) production and subsequent mtROS-mediated NF-κB activity in Kupffer cells (KCs). ZC reduced mRNA levels of pro-inflammatory cytokines (Il1b and Tnfa) and chemokines (Ccl2, Ccl3, Ccl4, Cxcl2 and Cxcl9). Tumor necrosis factor (TNF)-α-induced hepatocyte mtROS production was inhibited by ZC. ZC was effective in alleviating mtROS-mediated mitochondrial dysfunction. ZC enhanced mitophagy and increased mRNA levels of fatty acid oxidation genes (Pparα, Cpt1, Acadm and Hadha) and mitochondrial biosynthetic factors (Pgc1α, Tfam, Nrf1 and Nrf2) in hepatocytes. ZC has proven its anti-lipid effect by improving lipid accumulation in hepatocytes by enhancing mitochondrial function to facilitate lipid metabolism. Therefore, our study suggests that ZC may be an effective compound for hepatoprotection by suppressing inflammation and lipid accumulation through regulating mtROS. Full article

Surface suction provides an efficient way to delay boundary layer transitions. In order to verify the suction effects and determine the mechanism of suction control in transonic swept wing boundary layers, wind tunnel transition measurements in a hybrid laminar flow control (HLFC) wind tunnel model uses an infrared thermography technique in the Aircraft Research Association (ARA) 2.74 m × 2.44 m low turbulence level transonic wind tunnel. Based on the experimental data of stationary crossflow dominant transitions without and with surface suction in transonic swept wing boundary layers, in this paper, the effects on the receptivity and linear and nonlinear evolution of stationary crossflow vortices have been analyzed with the consideration of curvature. Theoretical analysis agreed with the experimental observations in regard to the transition delay caused by boundary layer suction near the leading-edge region. Full article

The marine and alluvial plains along the southeastern coast of China are widely distributed in sandy formations, including smaller sand lenses and interlayers. The interlayers of sand have a significant impact on the mechanical properties of soft clay. In this paper, a large number of undrained unidirectional and bidirectional cyclic loading tests for soft clay with sand interlayers were carried out by a dynamic triaxial test system. Test results show that, under unidirectional and bidirectional cyclic vibration, the area of the hysteresis loop decreases and the slope of the connecting line at both ends of the hysteresis loop increases with the increasing of frequency. For the same vibration frequency, the area of the bidirectional vibration hysteresis loop and the slope of the connecting line at both ends are smaller than that of the unidirectional cyclic vibration. Under the same dynamic stress ratio, cumulative axial deformation caused by unidirectional and bidirectional vibration increases with the increasing frequency. Under unidirectional vibration, dynamic elastic modulus decreases at first, and then increases with the increasing frequency. For the same frequency, dynamic elastic modulus of the sample increases with the increase in cycles. Due to the effect of radial cyclic stress, the curves of dynamic elastic modulus and damping ratio with frequency under bidirectional vibration are opposite to those under unidirectional vibration. Full article

Conveyor belts are widely used in ore transportation in large-scale mines for their long transportation range, high safety, and strong economic applicability. Coal mine belt conveyors are not only traditional, simple mechanical conveying devices but also automatic control system operating devices that integrate safety, stability, and low power consumption. In the process of coal mining, a conveyor belt control system also needs to be closely integrated with modern industrial systems and information systems, which greatly improves its work efficiency. The purpose of this article is to improve the methods for designing automatic control systems for electric motors in order to obtain mechanical characteristics close to a constant power line, which would ensure the reliable operation of belt conveyors. An automatic control system was designed based on the controller Siemens S7-1200; then, a mathematical model of an automated electric drive was developed. Based on the mathematical model, a simulation model of an automatic electric drive was built, and the modes were modeled. After designing, the obtained plots of transients completely corresponded to the required transients, which means that the Siemens frequency converter automatic control system (ACS) parameters were calculated quite accurately and the conveyor electric drive met all requirements. Full article

Construction machinery, which is widely used in infrastructure construction, is growing rapidly all over the word. However, the complex working conditions of construction machinery lead to serious wear, particularly the wear of the bucket teeth on construction machinery. To control the wear procedure, it is essential to understand the wear mechanism and identify the wear form under variable working conditions. The modeling methods of bucket tooth wear with different wear mechanisms were reviewed. The modeling methods were divided into the analytical method and the numerical simulation method. The numerical simulation method included the discrete element method, finite element method, SPH method, and so on, which were used to simulate the bucket digging process and analyze the interaction between the material and bucket teeth during the working process. This enabled a force analysis of the bucket digging process and the identification of the location of maximum wear. By establishing a wear model, it is possible to better understand and address the wear problem in construction machinery. This article aims to summarize research methods concerning the wear of wear parts in construction machinery. It provides a theoretical foundation for future investigations in this area and aims to address challenges such as lengthy wear life testing, numerous interfering factors, and the difficulty of data collection pertaining to wear parts. Full article

α-Mangostin, a natural xanthone, was found to have anticancer effects, but these effects are not sufficient to be effective. To increase anticancer potential and selectivity, a triphenylphosphonium cation moiety (TPP) was introduced to α-mangostin to specifically target cancer cell mitochondria. Compared to the parent compound, the cytotoxicity of the synthesized compound 1b increased by one order of magnitude. Mechanistic analysis revealed that the anti-tumor effects were involved in the mitochondrial apoptotic pathway by prompting apoptosis and arresting the cell cycle at the G0/G1 phase, increasing the production of reactive oxygen species (ROS), and reducing mitochondrial membrane potential (Δψ_m). More notably, the antitumor activity of compound 1b was further confirmed by zebrafish models, which remarkably inhibited cancer cell proliferation and migration, as well as zebrafish angiogenesis. Taken together, our results for the first time indicated that TPP-linked 1b could lead to the development of new mitochondrion-targeting antitumor agents. Full article

The transmission and infectivity of COVID-19 have caused a pandemic that has lasted for several years. This is due to the constantly changing variants and subvariants that have evolved rapidly from SARS-CoV-2. To discover drugs with therapeutic potential for COVID-19, we focused on the 3CL protease (3CL^pro) of SARS-CoV-2, which has been proven to be an important target for COVID-19 infection. Computational prediction techniques are quick and accurate enough to facilitate the discovery of drugs against the 3CL^pro of SARS-CoV-2. In this paper, we used both ligand-based virtual screening and structure-based virtual screening to screen the traditional Chinese medicine small molecules that have the potential to target the 3CL^pro of SARS-CoV-2. MD simulations were used to confirm these results for future in vitro testing. MCCS was then used to calculate the normalized free energy of each ligand and the residue energy contribution. As a result, we found ZINC15676170, ZINC09033700, and ZINC12530139 to be the most promising antiviral therapies against the 3CL^pro of SARS-CoV-2. Full article

(1) Background: With the resurgence of brucellosis epidemics in China in recent years, the chances of a brucella coinfection with other common respiratory pathogens, such as the influenza virus, have increased dramatically. However, little is known about the pathogenicity or the mechanisms of brucella and influenza coinfections. (2) Methods: To clarify the interventions in the early stages of lung damage due to brucella and influenza coinfections, we evaluated the effect of the coinfection on disease progression and mortality using a coinfection model in WT mice and NLRP6^−/− mice, and we verified the function of NLRP6 in infection and proinflammation. (3) Results: The coinfection induced significant respiratory symptoms, weight loss, and a high mortality rate in WT mice. Influenza in the coinfection group significantly increased brucella proliferation in a synergistic manner. Meanwhile, a histological examination showed severe lung tissue destruction and excessive inflammatory responses in coinfected WT animals, and the expression of NLRP6 and IL-18 was dramatically increased in the lung tissues. Furthermore, NLRP6 deletion attenuated lung injuries and inflammation, a reduced bacterial load, and decreased IL-18 protein expression. (4) Conclusions: Our findings indicated that NLRP6 plays a critical role and might be a promising potential therapeutic target for brucella–influenza coinfections. Full article

Prediction on drug–target interaction has always been a crucial link for drug discovery and repositioning, which have witnessed tremendous progress in recent years. Despite many efforts made, the existing representation learning or feature generation approaches of both drugs and proteins remain complicated as well as in high dimension. In addition, it is difficult for current methods to extract local important residues from sequence information while remaining focused on global structure. At the same time, massive data is not always easily accessible, which makes model learning from small datasets imminent. As a result, we propose an end-to-end learning model with SUPD and SUDD methods to encode drugs and proteins, which not only leave out the complicated feature extraction process but also greatly reduce the dimension of the embedding matrix. Meanwhile, we use a multi-view strategy with a transformer to extract local important residues of proteins for better representation learning. Finally, we evaluate our model on the BindingDB dataset in comparisons with different state-of-the-art models from comprehensive indicators. In results of 100% BindingDB, our AUC, AUPR, ACC, and F1-score reached 90.9%, 89.8%, 84.2%, and 84.3% respectively, which successively exceed the average values of other models by 2.2%, 2.3%, 2.6%, and 2.6%. Moreover, our model also generally surpasses their performance on 30% and 50% BindingDB datasets. Full article