Latest ArticlesCalcium-dependent protein kinases (CDPKs) serve as crucial calcium sensors in plants, playing key roles in regulating plant growth, development, and stress responses. In this study, a total of 26 Salvia miltiorrhiza CDPK (SmCDPK) genes were identified through genome-wide analysis, which were unevenly distributed across seven chromosomes. Phylogenetic analysis grouped the 26 SmCDPKs into four distinct subfamilies (Ⅰ-Ⅳ), and systematic predictions were conducted for their physicochemical properties, secondary structures, and subcellular localization. Promoter analysis uncovered multiple cis-elements associated with light, phytohormones, and abiotic stress. Transcriptome profiling under 50 and 100 μmol·L-1 cadmium (Cd) stress demonstrated tissue-specific expression patterns of these SmCDPK genes. Notably, SmCDPK18 was upregulated in both roots and leaves under Cd exposure, suggesting involvement in Cd detoxification and oxidative regulation. In contrast, SmCDPK2, SmCDPK8, and SmCDPK22 were significantly downregulated in roots. These expression patterns were confirmed by quantitative reverse-transcription PCR (qRT-PCR). This study provides insight into the CDPK gene family in S. miltiorrhiza and its potential roles in cadmium stress response, offering valuable theoretical support and key gene resources for future molecular breeding and environmental adaptation studies in medicinal plants.
Rheum officinale Baill., one of the three primary botanical sources of medicinal rhubarb in China, is mainly cultivated in high-altitude regions. However, the regulatory mechanisms underlying the biosynthesis of its major active constituents, anthraquinones, remain poorly understood. UV-B radiation (280-315 nm) is a key ecological factor in high-altitude habitats, profoundly affecting the quality formation of R. officinale. Identifying UV-B-responsive genes is therefore essential for elucidating the regulatory pathways involved. The basic leucine zipper (bZIP) transcription factor family is known to regulate plant growth and development, secondary metabolite biosynthesis, and stress responses; however, a comprehensive analysis in R. officinale is still lacking. In this study, we conducted a genome-wide identification of the bZIP gene family in R. officinale, and systematically analyzed the physicochemical properties, gene structures, phylogenetic relationships, and conserved motifs. Transcriptome data were utilized to identify RobZIPs highly expressed in roots and rhizomes and responsive to UV-B radiation, followed by experimental validation. A total of 94 RobZIPs were identified, unevenly distributed across 10 chromosomes except chromosome 8, with 36 tandem duplication events observed. All RobZIP-encoded proteins are predicted to be hydrophilic, comprising 64 to 780 amino acids, and are primarily localized in the nucleus. Phylogenetic analysis classified the RobZIP genes into 11 subgroups, with members within the same subgroup exhibiting similar gene structures and conserved motifs. Collinearity analysis revealed that tandem duplication is the primary mode of expansion for the RobZIP gene family. Promoter cis-element analysis identified numerous elements associated with plant development, hormone signaling, and stress responses in RobZIPs. qRT-PCR analysis confirmed the tissue-specific expression and UV-B responsiveness of 8 RobZIPs, including RobZIP15, consistent with transcriptomic data. This study provides a comprehensive analysis of the bZIP gene family in R. officinale, laying the foundation for further investigations into their evolutionary dynamics, UV-B response mechanisms, and potential roles in anthraquinone biosynthesis.
The activating transcription factor (ATF) family, a key branch of the basic leucine zipper (bZIP) transcription factors, is widely involved in various biological processes including cellular stress responses, inflammation, apoptosis, and metabolism. In the pathogenesis and progression of pulmonary fibrosis and inflammatory lung diseases, such as acute lung injury/acute respiratory distress syndrome, chronic obstructive pulmonary disease, asthma, ATF family members regulate critical mechanisms including cellular stress, inflammatory responses, and ferroptosis, thereby influencing immune responses and tissue remodeling. They exhibit bidirectional regulatory roles with both pathological promotion and protective effects. This review summarizes the expression changes, biological functions, and potential molecular mechanisms of ATF family members in inflammatory lung diseases and pulmonary fibrosis, aiming to offer novel research perspectives for developing mechanism-based targeted therapies for pulmonary diseases.
Ischemic stroke (IS) remains a leading cause of mortality and disability among adults worldwide, with its core pathological mechanism rooted in ischemic-hypoxic neuronal injury triggered by cerebral blood flow interruption. Current clinical treatments primarily rely on intravenous thrombolysis and endovascular thrombectomy. However, these approaches are constrained by strict therapeutic time windows (typically ≤ 4.5 h), bleeding risks in certain patients, and limited neurorestorative effects following reperfusion. Despite active development of neuroprotective agents and anti-inflammatory drugs in recent years, most have failed in clinical translation due to insufficient efficacy or safety concerns, highlighting the complexity of disease mechanisms and limitations of preclinical evaluation systems. Consequently, developing therapeutics that simultaneously address reperfusion protection and neural repair by targeting the pathological cascade of IS has emerged as a critical direction to overcome current therapeutic bottlenecks. This review synthesizes recent advances in domestic and international IS drug development in recent years, focusing on model establishment, efficacy evaluation metrics, and relevant molecular mechanisms to systematically summarize the preclinical pharmacodynamic evaluation framework for IS therapeutics. The findings provide valuable insights for optimizing preclinical evaluation systems, accelerating drug development, and expanding effective clinical treatment strategies for IS.
As first-line drugs for inhibiting gastric acid and treating digestive system diseases, proton pump inhibitors (PPI) have been found in recent studies to have multi-pathway effects on the regulation of metabolic diseases. There are both therapeutic potentials and risks in the prevention and treatment of metabolic diseases. Studies have indicated that PPI participate in the pathophysiological processes of obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) through multiple regulatory mechanisms, including reducing levels of appetite-related hormones, improving insulin sensitivity, decreasing hepatic fat accumulation, and modulating fibrotic progression. However, long-term use of PPI has potential risks, including electrolyte disorders, intestinal flora imbalance, osteoporosis, increased risk of fractures, and increased risk of cardiovascular diseases. In clinical application, the medication regimen should be precisely formulated based on the individual characteristics of patients, long-term use without indications should be avoided, and relevant risks should be closely monitored.
High-throughput screening (HTS) has been widely used in drug discovery recently. It allows batch bioactivity testing of compounds, thereby accelerating the identification of bioactive molecules. However, its screening efficiency and accuracy remain limited. Therefore, artificial intelligence (AI) is gradually integrated into the process of HTS, such as machine learning and deep learning algorithms to enhance ligand-based virtual screening, drug combination screening, and analysis of images, to promote the intelligent development of drug discovery. This review summarized the recent advances in the application of AI technologies in HTS, discussed the applications of machine learning models, and highlighted key AI applications in compound screening and recognition of image in HTS to accelerate the development of innovative drugs.
Tetramic acid unit occurred in a large number of natural products, which normally exhibited antitumor, anti-ulcer, antibacterial, antiviral, and herbicidal activities. Their complex and diverse molecular structures as well as broad biological activities have attracted great attention from biochemists. This article reviewed the natural products with tetramic acid structures isolated since 2013, classified them based on their structures, and introduced their biological activities.
Chemotherapy-induced nausea and vomiting (CINV) represents one of the most prevalent adverse reactions during cancer treatment. Its pathological mechanism is complex, involving multiple neurotransmitters and their biopathways, such as serotonin, substance P, and dopamine, along with their respective receptors. Existing chemical agents for CINV prophylaxis and management face challenges including limited efficacy, serious side effects, and high cost. In contrast, traditional Chinese medicine (TCM) holds considerable promise for CINV prevention and treatment, leveraging advantages such as multi-components, multi-targets, high safety, low side effects, and cost-effectiveness. The structural classes, mechanisms of action, structure-effect relationships, and clinical applications for currently available CINV drugs were systematically reviewed. Moreover, the recent research progress on TCM for preventing and treating CINV was also introduced It will provide significant references for the development of novel CINV therapeutics with sustained efficacy, high efficiency, and low cost.
The voltage-gated sodium channel isoform Nav1.8 is predominantly distributed in peripheral injurious sensory neurons and plays a key regulatory role in the development and maintenance of acute and chronic pain and neuropathic pain. In January 2025, suzetrigine, the first analgesic drug targeting Nav1.8, was approved for marketing in the United States FDA, marking a major breakthrough in the development of Nav1.8-targeted pain therapeutics. The successful development of the first analgesic for Nav1.8 has led to a global interest in the development of Nav1.8 analgesic inhibitors. This article reviews the structure, physiological function, and drug development of Nav1.8. We focus on summarizing the electrophysiological properties of Nav1.8, its role in pain, and the clinical studies of selective inhibitors, aiming to provide a reference for the development of Nav1.8 analgesics.
This article conducted a comparative analysis of the background and fundamental differences between the 505(b)(2) drug and modified new drug, with a focus on successful case studies of 505(b)(2) drugs, discussing clinical requirements and development trends. Based on the national conditions of our country, the project initiation considerations and examples of improved new drugs were carried out from the perspective of preparations. Additionally, the causes of improvement failures and relevant cases were analyzed and discussed, providing critical insights to advance the development of modified new drug in China.
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