Latest ArticlesThirteen compounds were isolated from Armeniacae Semen Amarum using macroporous resin column chromatography combined with semipreparative high performance liquid chromatography. Their structures were identified as trans-4-O-(β-D-gentiobiosyl)-p-coumaric acid (1), trans-4-O-(β-D-gentiobiosyl) ferulic acid (2), hazelnutin F (3), amygdalinamide (4), prunasinamide (5), benzyl-β-gentiobioside (6), (S)-mandelamide (7), amygdalinic acid (8), L-phenylalanine (9), L-tryptophan (10), amygdalin (11), L-amygdalin (12), and prunasin (13) by spectroscopic methods including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR), as well as comparison with literature data. Among them, compounds 1 and 2 were identified as new compounds.
This study established a discrete element method (DEM) parameter calibration approach for fermented Cordyceps powder and investigated the mechanism by which binary mixture systems affect flowability. The angle of repose, measured via physical experiments, served as the response value. Using the Hertz-Mindlin with JKR V2 contact model, the optimal DEM simulation parameters were identified through a sequential methodology comprising Plackett-Burman design, steepest ascent experiments, and Box-Behnken response surface methodology. Based on this calibrated model, binary angle of repose simulations was constructed with large particles (1.404 mm) as the skeleton and small particles (0.228 mm) as the filling phase, at mass ratios of 85∶15, 90∶10, and 95∶5. A mesoscopic mechanical analysis was subsequently performed. Simulation results indicate that the binary mixing method effectively optimizes the fermented Cordyceps powder's flowability. Furthermore, appropriately reducing the proportion of small particles contributes to enhancing the overall system flowability, with the 95∶5 mass ratio representing the optimal balanced state. From a mesoscopic perspective, the observed macroscopic trend is closely related to the reconstruction of the internal force chain architecture from a "weak connection network" to a "strong force chain skeleton". Concurrently, a decrease in the coordination number suggests a reduction in geometric constraints between particles, while the contact stress ratio (Ft/Fn) remains in a subcritical stable state. These factors collectively contribute to the optimized flowability. This study successfully established a DEM model for the flow behavior of fermented Cordyceps powder, elucidated the mechanism of binary mixture systems from the mesoscopic level, and provided a reference for the binary simulation of other fermented Cordyceps powder systems.
Ketorolac tromethamine (KT) is characterized by a short half-life and rapid systemic clearance, necessitating frequent dosing when administered via traditional oral or injectable routes, and is associated with pronounced first-pass metabolism and gastrointestinal adverse effects. To mitigate these limitations, this study developed ketorolac tromethamine microneedles (KTMN) for buccal mucosal delivery and evaluated their analgesic efficacy. The microneedle tips were fabricated using a photosensitive hyaluronic acid methacrylate solution as the matrix, which was cast into polydimethylsiloxane molds, followed by drying and UV crosslinking to yield well-formed KTMNs. Each microneedle exhibited a mechanical strength of 0.70 N and achieved a penetration depth of 120 μm in rat buccal mucosa. In artificial saliva, KTMNs demonstrated sustained and stable drug release, with an in vitro release rate of 55.33% at 2 h and 76.77% at 12 h. Pharmacokinetic analysis revealed a peak plasma concentration of 5.91 μg·mL-1 at 2 h post-administration, with an average residence time extending up to 15.52 h. In vivo, KTMN administration significantly attenuated pain responses in both the formalin-induced pain model and the carrageenan-induced inflammatory pain model in rats. Overall, buccal mucosal delivery of KTMNs represents a safe, rapid, and efficient formulation, offering a promising new strategy for fast-acting, long-lasting, and convenient analgesia.
α-Humulene is a natural sesquiterpenoid with multiple pharmacological activities including anti-inflammatory, antibacterial and antitumor effects, and also serves as the key precursor for zerumbone biosynthesis. In this study, Saccharomyces cerevisiae was used as the chassis for heterologous production of α-humulene. One novel α-humulene synthase gene, AsTPS8, was mined from the transcriptome of Aquilaria sinensis. Compared with the reported ZSS1 from Zingiber zerumbet, AsTPS8 exhibited higher catalytic efficiency. Furthermore, fusion expression of ERG20 with AsTPS8 via a (GGGS)2 linker combined with multi-copy integration at the TY1 locus increased the α-humulene titer to 1.41 g·L-1 in shake flasks. On this basis, the bypass phosphatase gene LPP1 was knocked out using CRISPR/Cas9, and the transcriptional regulators IME4 and UPC2-1 were simultaneously introduced, further elevating the titer to 1.80 g·L-1. Finally, fed-batch high-density fermentation in a 5 L bioreactor achieved an α-humulene titer of 22.02 g·L-1 at 144 h, representing the highest reported level to date. This study provides an efficient chassis strain and technical support for the industrial production of α-humulene and downstream zerumbone.
Cancer is a highly heterogeneous malignant disease. Currently, precision medicine in oncology urgently requires experimental models that can faithfully simulate the individual tumor characteristics of patients. Traditional two-dimensional cell lines and animal models exhibit significant limitations in preserving tumor heterogeneity, microenvironment, and predicting treatment responses. Organoid technology, with its three-dimensional structure and high fidelity in recapitulating the histopathological and molecular features of primary tumors, has emerged as a transformative tool in cancer research. This review systematically outlines the development of organoid technology, highlighting the methodologies and applications for modeling various solid tumors, including lung cancer, breast cancer, gastric cancer, renal carcinoma, and colorectal cancer. It encompasses multiple aspects such as investigations into tumorigenesis mechanisms, drug screening, personalized therapy, and immunotherapy assessment. Furthermore, the current challenges and future directions of organoid technology are discussed, with the aim of promoting its broader application in cancer research and clinical translation.
As a core biological process for the repair of liver injury, liver regeneration represents a key breakthrough in the treatment of liver failure and end-stage liver disease. Its mechanistic complexity and therapeutic translation potential have long been research hotspots. In recent years, with the advancement of molecular biology and regenerative medicine technologies, significant progress has been made in liver regeneration research, including mechanistic elucidation, identification of regulatory targets, and development of therapeutic strategies. This article systematically reviews the molecular mechanisms and therapeutic strategies of liver regeneration, analyzes current research bottlenecks, and discusses future directions, aiming to provide a reference for scientific research and clinical applications in this field.
As significant bioactive constituents within natural products, alkaloids exhibit characteristics of extensive sources, diverse structures, multi-targeted and multi-level actions, and possess potent immunomodulatory effects. Although numerous studies have explored the pharmacological effects and mechanisms of alkaloids, a systematic review of their immunomodulatory activities and underlying mechanisms remains to be systematically reviewed, particularly an integrative analysis of the most recent research advances. Therefore, this paper collates recent research findings on alkaloids within the field of immunoregulation. It reviews the modulatory effects of alkaloids on the immune system, summarises the principal molecular mechanisms underlying their actions, and outlines their applications in the treatment of immune-related diseases. This review aims to provide a reference for subsequent mechanistic studies and the development of related pharmaceuticals.
Stroke is characterized by high incidence, high disability, high mortality, and high recurrence rates. Current clinical management relies primarily on injectable thrombolytic therapy. While a variety of oral adjuvant medications are available, their therapeutic efficacy and underlying mechanisms have not been systematically evaluated. Traditional Chinese medicine (TCM), as a multi-component and multi-target therapeutic option, has demonstrated considerable potential in the prevention and treatment of stroke. Emerging evidence indicates that TCM exerts modulatory effects on stroke-related pathological processes by regulating the gut microbiota, maintaining gastrointestinal homeostasis, and acting through the gut-brain axis. The conventional pharmacological paradigm holds that drugs must enter the systemic circulation and traverse the blood-brain barrier (BBB) to exert central effects. Despite their low oral bioavailability and limited systemic exposure, certain pharmacologically active constituents nonetheless exert significant neuroprotective effects, suggesting that their in vivo activities may be mediated by indirect gut-derived regulatory mechanisms rather than direct systemic actions. Based on these observations, we propose the concept of "intestinal retention components" (IRC), referring to a class of orally administered bioactive constituents that are poorly absorbed across the intestinal epithelium and predominantly retained within the intestinal lumen due to their physicochemical properties. Although these compounds exhibit minimal systemic exposure, they are capable of modulating the intestinal microenvironment, thereby influencing brain function and improving stroke outcomes. This review aims to systematically elucidate the potential mechanisms by which IRC indirectly exerts anti-stroke effects via the gut-brain axis, encompassing microbiota-mediated biotransformation, attenuation of gut microbial dysbiosis and its associated metabolic perturbations, restoration of intestinal barrier integrity, and regulation of the intestinal mucosal immune microenvironment. Given that numerous central nervous system disorders are also accompanied by intestinal microenvironmental dysregulation, the IRC-centered research framework targeting the gut microenvironment may provide a valuable reference for mechanistic elucidation and the identification of candidate drugs among orally active constituents in the context of broader neurological diseases.
The mixed lineage kinase domain-like protein (MLKL) is a "pseudokinase" that not only functions as a key effector molecule in the necroptosis pathway but also participates in the regulation of other programmed cell death pathways, thereby playing a crucial role in modulating various physiological processes. Dysregulation of MLKL activity is closely associated with the initiation and progression of multiple diseases, rendering it a highly promising therapeutic target. However, drug discovery targeting MLKL is still in its early stages, with no candidates having advanced to clinical trials. Thus, further in-depth and systematic investigations are urgently needed. This review summarizes the structural features, biological functions, and current progress in drug development targeting MLKL.
As a prominent class of nitrogen-containing heterocycles, 1,3,5-triazines are characterized by their rigid, symmetrical structures, ease of functionalization, exceptional biological activities, making them a privileged scaffold in medicinal chemistry. This paper provides a systematic review of the research progress on 1,3,5-triazine derivatives over the past five years (2021-2025), covering their structure-activity relationships and mechanisms of action. Results indicate that 1,3,5-triazine compounds exhibit promising antimicrobial activity against methicillin-resistant Staphylococcus aureus, drug-resistant Escherichia coli, and Candida albicans. Furthermore, certain 1,3,5-triazine compounds target PD-L1, PI3K/mTOR, or EGFR, thereby inducing apoptosis or cell cycle arrest and inhibiting tumor cell growth. In addition, these compounds also have anticonvulsant, neuroprotective, antimalarial, antihyperglycemic, and anti-inflammatory properties. However, several 1,3,5-triazine compounds lack clear mechanisms and possess unsatisfactory efficacy, requiring further in-depth research to develop new chemical entities.
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