Sorafenib serves as a first-line treatment for advanced hepatocellular carcinoma (HCC), advanced renal cell carcinoma (RCC), and radioactive iodine-refractory differentiated thyroid carcinoma (DTC). While it improves patient prognosis by inhibiting tumor cell proliferation and angiogenesis, approximately 70% of patients experience limited efficacy within 6 months of treatment due to primary or acquired resistance mechanisms. These mechanisms include abnormal activation of core signaling pathways, epithelial-mesenchymal transition (EMT), dysregulated ferroptosis, aberrant drug transport and metabolism, and abnormal regulation of the tumor microenvironment (TME). Based on resistance mechanism subtypes, this systematic review summarizes recently reported extracts from traditional Chinese medicine (TCM) and natural product monomers that demonstrate the potential to reverse sorafenib resistance. It further provides an in-depth analysis of the current challenges in resistance research. These challenges encompass the mismatch between pharmacokinetic properties and resistance mechanism subtypes (e.g., precipitation of lipophilic components in the acidic TME, metabolic competition), the unclear core targets and cooperative interaction patterns within resistance subtypes (e.g., undefined contribution of multiple mechanisms), and the lack of standardization and continuity in clinical trials and translation (e.g., absence of subtype stratification, disconnection between quality standards and mechanisms). To address these challenges, this review proposes innovative directions, including the development of mechanism-oriented customized drug delivery systems, multi-omics-driven elucidation of core targets and construction of cooperative networks, and the establishment of clinical translation systems stratified by resistance mechanism subtypes. This review aims to provide insights for deepening fundamental research on the combination of TCM/natural products with sorafenib for treating advanced cancer and to promote its standardized clinical application, thereby fostering the development of integrated Chinese-Western medicine strategies in oncology.

Diabetic kidney disease is a significant microvascular complication of diabetes that can progress to end-stage renal disease, severely threatening patients' quality of life and longevity. Its pathogenesis is complex, involving multiple pathways including inflammatory responses, oxidative stress, metabolic disorders, and disrupted intercellular signaling networks in the kidney, all significantly influenced by individual variability. Current clinical treatment options remain limited, with a lack of targeted effective drugs posing substantial challenges for prevention and management. This systematic review examines the pathogenesis and existing treatment strategies for diabetic kidney disease. By integrating recent advances, it explores emerging therapeutic approaches and potential breakthrough directions, aiming to provide a theoretical and practical foundation for innovative interventions and clinical translation.

Liquid-liquid phase separation (LLPS) serves as a key mechanism driving numerous essential biological processes. In eukaryotic cells, LLPS facilitates the formation of membraneless organelles (MLOs) by promoting the local enrichment of biomacromolecules such as proteins and nucleic acids, thereby establishing compartmentalization to enhance biochemical reaction efficiency. Under stress conditions, it also helps protect critical cellular components, including mRNA and proteins. Growing evidence in recent years indicates that LLPS-driven biomolecular condensation similarly occurs in prokaryotes. For instance, under environmental stresses (such as oxidative stress, nutrient deprivation, or antibiotic exposure), bacteria can form biomolecular condensates via LLPS that perform MLOs-like functions, improving the stress adaptability of bacteria. Proposed protective mechanisms include shielding proteins from irreversible inactivation or degradation, activating protein quality control systems, and inducing a dormant state to promote survival. Moreover, under physiological conditions, LLPS is involved in core cellular processes in bacteria, such as plasmid partitioning, chromosome segregation, transcriptional regulation, cell division, DNA replication, and repair. This review systematically summarizes the mechanisms by which biomolecular aggregates form in bacteria under both physiological and stress conditions, with a focus on how LLPS-mediated phase transitions enhance bacterial fitness and environmental adaptability. We also aim to provide insights into novel antibacterial strategies targeting LLPS.

CD4⁺ T cell-mediated immune inflammatory responses play a significant role in the development and progression of atherosclerosis (AS). CD4⁺ T cells can differentiate into multiple subtypes, such as pro-inflammatory Th1/Th17 cells and anti-inflammatory Th2/Treg cells, and the imbalance between these subtypes determines the direction of progression of AS. Increasingly, studies have shown that metabolic reprogramming of CD4⁺ T cells induces their pro-inflammatory differentiation, exacerbates vascular microenvironmental inflammation and plaque instability, and thus promotes the development of AS. In this review, we shall focus on the relationship between CD4⁺ T cell metabolic reprogramming-mediated cellular differentiation, functional alterations, and the onset and progression of AS. We shall also examine therapeutic strategies targeting CD4⁺ T cell metabolism in AS. This will provide evidence for elucidating the mechanisms underlying vascular inflammation in AS and offer guidance for identifying novel targets and approaches for the prevention and treatment of AS in clinical practice.

Metallo-β-lactamases (MBLs) mediate carbapenem antibiotic resistance by hydrolyzing the β-lactam ring. However, existing inhibitors remain largely confined to laboratory research due to poor selectivity or insufficient potency, and no clinically approved MBL inhibitors are currently available. MBLs are categorized into three subclasses B1, B2, and B3. B1 and B3 subclasses possess a binuclear zinc catalytic center, whereas B2 harbors a single active zinc ion. Despite their structurally conserved active sites featuring a characteristic αβ/βα-fold architecture with catalytic zinc ions positioned between αβ units flanked by flexible loops. Meanwhile, candidates developed through enzymatic and thermodynamic studies, such as 2-quinazolinone QDP-1, boronic acid derivatives VNRX-5133/QPX7728, thiazolecarboxylic acid ANT2681, and selenium-containing compound SPI-1005, still face challenges in achieving broad-spectrum efficacy and clinical safety. This review systematically examines the interaction mechanisms between inhibitors and MBLs, focusing on three strategic approaches: Covalent binding strategies, zinc ion chelation, and allosteric inhibition. The synthesis aims to provide theoretical foundations and rational design strategies for developing potent, safe, and broad-spectrum metallo-β-lactamase inhibitors.

Since its introduction to the market, etomidate has held a significant position among intravenous anesthetics due to its favorable anesthetic properties and hemodynamic stability. However, adverse reactions like adrenocortical suppression and myoclonus have limited its clinical application. In recent years, the research on novel etomidate derivatives that can retain the excellent anesthetic characteristics of etomidate while significantly ameliorating its adverse effects has become a hot topic in the development of new anesthetic drugs. Through the structural modification of pharmacophores such as the carboxylic acid ester chain and imidazole ring, new derivatives, including ABP-700, EL-0052, ET-26, and NH600001, have been discovered. Some of these drugs have entered the phase Ⅲ clinical trial or NDA application stage, showing promising prospects for successful development and marketing approval. This article reviews the design strategies, preclinical research, and clinical research progress of etomidate derivatives, aiming to provide references for the development of new intravenous anesthetics.

Calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) is a key enzyme mediating cardiac diseases such as arrhythmia, ischemic heart disease, and heart failure. Its involvement in the progression of cardiac diseases has become increasingly clear with advancing research. Targeted regulation of cardiac CaMKⅡ has become a major therapeutic strategy for heart diseases. However, traditional drug delivery strategies suffer from poor cardiac targeting and low local concentrations, necessitating the integration of innovative delivery and release systems. This review first describes the CaMKⅡ and its role in cardiac diseases, and then provides a systematic review of the design and research progress of cardiac-targeted nanodelivery systems, with the aim of offering new insights into the targeted regulation of cardiac CaMKⅡ and the development of innovative cardiac disease therapies.

Nucleic acid therapeutics, as a transformative modality in modern biopharmaceuticals, mediate disease treatment through precise gene expression modulation. Their remarkable therapeutic potential, such as in oncology, has been demonstrated clinically. The regulatory approval of nucleic acid drugs, exemplified by the SARS-CoV-2 mRNA vaccines, has not only validated their clinical translation potential, but also accelerated advancements in nucleic acid drug development platforms. The functional efficacy of nucleic acid drugs is fundamentally governed by their three-dimensional structural architecture, necessitating rigorous stability assessments throughout the development pipeline. Critical considerations include maintaining native conformation during delivery, achieving target-specific release profiles, and optimizing storage formulations for long-term stability. Circular dichroism (CD) spectroscopy has emerged as an indispensable analytical tool due to its exceptional sensitivity to chiral environments. CD enables precise detection of nucleic acid structural transitions, from base-stacking interactions to complex higher-order conformational changes, making it invaluable for structural characterization. This review summarizes recent research progress on the typical conformational characteristics of nucleic acid drugs and the factors influencing their stability. It focuses particularly on methodological advances in CD spectroscopy for structural analysis and quality control, providing critical insights to guide future research in this rapidly evolving field.

Resveratrol (Res), a naturally non-flavonoid polyphenol, shows significant therapeutic potential in suppressing tumor growth, metastasis, and enhancing chemotherapy. However, Res has some disadvantages that limit its clinical use, such as low oral bioavailability, structural instability, and non-selective tissue distribution in vivo. Stimuli-responsive drug delivery systems can overcome these issues, achieving efficient delivery in vivo and controlled release at tumor-site. Based on the endogenous physiological features of tumors and exogenous stimulation methods, this paper uses Res as an example, which reviews the current response release methods for targeted delivery of anti-tumor drugs, such as pH, ROS, and light-responsive strategies, respectively. The diversified release designs offer references for controlled release of anti-tumor drugs in the complex tumor microenvironment. It also provides new ideas and directions for personalized and smart treatment for anti-tumor active ingredients from traditional Chinese medicine.

Based on our previous finding that the traditional Chinese medicine Aglaia odorata Lour. exhibited therapeutic effects against ischemic stroke, this study aimed to identify its target proteins with stable isotope labeling by amino acids in cell culture (SILAC) combined with thermal proteome profiling (TPP) strategy using oxygen-glucose deprivation/reperfusion (OGD/R) model of rat adrenal pheochromocytoma (PC12) cell, and explore the target-associated signaling pathways to reveal the molecular mechanisms underlying neuroprotective effects. The results showed that A. odorata exerted a protective effect on OGD/R-induced neuronal cell injury by significantly increasing the viability of PC12 cells and reducing lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels. Target identification revealed 28 proteins as potential targets of A. odorata, predominantly associated with energy metabolism-related signaling pathways, including carbon metabolism. Additionally, the verification results of the biological functions of the target group indicated that A. odorata increased the adenosine triphosphate (ATP) content in OGD/R-induced PC12 cells, enhanced the activity of mitochondrial respiratory chain complexes, elevated the mitochondrial membrane potential, reduced the production of mitochondrial superoxide, increased the phosphorylation of AMP-activated protein kinase (AMPK), and upregulated the protein expression of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In conclusion, A. odorata could alleviate OGD/R-induced neuronal cell injury and exhibit significant neuroprotective activity, possibly through the regulation of the AMPK/SIRT1/PGC-1α pathway and improvement of mitochondrial function and energy metabolism.

Diabetes mellitus is mainly caused by insufficient insulin secretion or impaired insulin action, and the patients exhibit varying degrees of pancreatic islet β-cell dysfunction. In the present study, Rin-m5F pancreatic islet β-cells were used to investigate the protective effect of puerarin against islet β-cell injury and its underlying mechanism. The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell viability, so as to screen the optimal concentrations of glucose (as the injury inducer) and puerarin (as the therapeutic agent). Flow cytometry was employed to evaluate the effect of puerarin on apoptosis in the glucose-induced islet β-cell injury model. Molecular docking technology was used to analyze the binding energy between puerarin and B-cell lymphoma-2 (Bcl-2) protein, and Western blot analysis was conducted to analyze the expression levels of Bcl-2 and its downstream-related proteins. The results of CCK-8 showed that 50 mmol·L^-1 glucose induced significant injury to Rin-m5F pancreatic islet β-cells, which was improved by puerarin (25-200 μmol·L^-1) in a dose-dependent manner. Flow cytometry results demonstrated that puerarin effectively reduced cell apoptosis. Molecular docking analysis revealed a favorable binding energy between puerarin and Bcl-2 protein. Further, Western blot results indicated that puerarin upregulated the expression of Bcl-2, while downregulated the expression of apoptotic pathway-related proteins, including Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase-3 (Caspase-3), and poly (ADP-ribose) polymerase 1 (PARP-1). Additionally, puerarin promoted the expression of microtubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ. After co-treated with Venetoclax, a Bcl-2 inhibitor, puerarin failed to protect against islet β-cell injury, inhibit apoptosis, and upregulate the expression of Bcl-2. These findings suggest that the protective effect of puerarin on islet β-cell injury is abrogated when Bcl-2 is inhibited. In conclusion, puerarin alleviates pancreatic islet β-cell injury by activating Bcl-2, providing a basis for the further investigation of the mechanism underlying the therapeutic effect of traditional Chinese medicine prescriptions containing Pueraria lobata in the treatment of diabetes mellitus.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. Current clinical treatments for PD remain limited, highlighting the urgent need for innovative drug development. In this study, we synthesized a protonic bis-pyridazine (H-Py) compound using an intermolecular proton transfer technique. In MPP⁺-induced PD model cells, H-Py significantly improved cell viability and reduced ROS levels. In 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model mice, H-Py demonstrated good safety and ameliorated motor dysfunction, with efficacy showing no significant difference from that of levodopa, a first-line PD therapeutic agent. Furthermore, immunofluorescence analysis of tyrosine hydroxylase (TH) levels in the substantia nigra and striatum revealed that H-Py administration significantly increased TH expression in these brain regions. Western blot analysis suggested that H-Py may protect against neuronal damage by activating the Nrf2/HO-1 pathway and alleviating oxidative stress. The experimental protocol was approved by the Animal Experiment Ethics Committee of Southwest University (approval No.: IACUC-20250714-05). In summary, this study may provide new strategies and insights for PD treatment.

Depression is a common mental disorder. Previous studies have found that Schisandra chinensis lignans (SCL) exhibit significant therapeutic effects on depression, though its antidepressant mechanisms remain incompletely understood. This study aims to elucidate the molecular mechanisms by which SCL exerts neuroprotective and antidepressant effects, based on SCL's modern pharmacological neuroprotective properties and the physiological function of cannabinoid type 1 receptor (CB1R) in neuronal protection. By establishing a chronic unpredictable mild stress (CUMS)-induced depression model and administering CB1R antagonist AM251 to CUMS-treated animals, we conducted pharmacobehavioral experiments to evaluate SCL's ability to improve depression-like behaviors in mice. Additionally, we employed Western blot, hematoxylin-eosin staining, immunohistochemistry, immunofluorescence, and molecular docking to investigate SCL's antidepressant mechanism through CB1R-mediated regulation of brain-derived neurotrophic factor (BDNF). The use of animals in this study was approved by the Ethics Committee of Shenyang Pharmaceutical University, with the approval number: SYPU-IACUC-C2021-11-3-115. Pharmacobehavioral results demonstrated that SCL alleviates depression-like behaviors in CUMS model mice. Hematoxylin-eosin staining revealed that SCL improves neuronal pathological damage and neuroplasticity impairment caused by CUMS in the model. Western blot analysis revealed that SCL upregulates BDNF and CB1R expression, activates the proBDNF-tPA-BDNF pathway to promote proBDNF cleavage, and exerts anti-apoptotic effects. It also activates BDNF-TrkB-MEK-ERK-PKA-CREB and PI3K-AKT pathways to reduce neuronal damage and exert antidepressant effects. Further experiments confirmed that AM251 antagonized SCL's antidepressant effects by inhibiting its depression-like behavior and modulation of BDNF-related pathways. Specifically, SCL activates proBDNF-tPA-BDNF via CB1R to enhance BDNF production and anti-apoptotic effects, while simultaneously activating the downstream classical pathway BDNF-TrkB-ERK-PI3K-AKT to protect neurons and exert antidepressant effects. Molecular docking revealed the binding sites of six major components in SCL for CB1R. The study revealed that SCL exerts antidepressant effects by regulating BDNF through CB1R to alleviate neuronal damage.

This study aimed to explore the multi-target mechanism of action of the innovative Chinese herbal compounds YCNHF Ⅰ (comprising 6 herbs with both edible and medicinal values, including Gardenia jasminoides and others)/Ⅱ (comprising 6 herbs without edible value, including Scutellaria baicalensis and others) in treating inflammatory bowel disease (IBD). We screened the active components of the compounds and IBD-related targets by mining multiple databases, then constructed a "compound-target-pathway" network and validated it using molecular docking. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to identify components that entered the bloodstream, and their antioxidant capacity was assessed. In lipopolysaccharide (LPS)-induced inflammatory Caco-2 cell models, we measured the expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β), as well as mitochondrial membrane potential. Additionally, we established a rat model of ulcerative colitis (UC) induced by dextran sulfate sodium (DSS), after administering the compounds via intragastric gavage, colonic pathology was observed via hematoxylin and eosin (HE) staining, and p-Akt expression in colon tissues was detected by Western blot. Results showed that YCNHF Ⅰ and YCNHF Ⅱ shared 191 and 186 common targets with IBD-related targets, respectively. These targets were mainly enriched in signaling pathways such as PI3K-Akt and in mitochondrial function regulatory networks. Components like quercetin showed strong binding affinity to targets including IL-6. The two compounds had 53 and 72 blood-entering components, respectively, exhibited antioxidant activity, inhibited pro-inflammatory factor expression, and improved mitochondrial membrane potential. They also alleviated pathological damage in UC rats and regulated the PI3K-Akt pathway. This experiment was approved by the Medical Ethics Committee of the Yan'an University (approval number: IIT-G-2025064).

This study explored the effect and mechanism of Dracocephalum moldavica L. on acute kidney injury (AKI) based on network pharmacology, molecular docking and animal experiments. Through online pharmacological studies, the effective components and targets of Dracocephalum moldavica L. in the treatment of AKI were obtained. Seventeen active components and 60 intersection targets were screened out, among which there were 12 core targets. Through the analysis of the function of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, it was screened out that it was mainly related to pathways such as cancer. Molecular docking was conducted between the active ingredients and the core targets. The results showed a strong association with matrix metalloprotein 9 (MMP9) and glycogen synthase kinase-3β (GSK-3β). The experiment selected the extract of Dracocephalum moldavica L. as the therapeutic drug and randomly divided ICR mice into normal group, model group, low, medium, and high (90, 180, 360 mg·kg^-1) dose groups of Dracocephalum moldavica L. extract, amifostine group (200 mg·kg^-1), and Uremic Clear Granules group (3 750 mg·kg^-1). Intragastric administration was given 7 days in advance. On the 7^th day, the amifostine group was injected with amifostine solution. Two hours after the end of intragastric administration on the 7^th day, except for the normal group, the other groups were intraperitoneally injected with cisplatin (CDDP) solution to establish an AKI mouse model. Samples were collected 72 hours after modeling. This experiment was approved by the Animal Ethics Committee of Xinjiang Institute of Materia Medica (approval number: XJIMM-20240802). The organ indices of liver, spleen, and kidney were calculated; the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) in mouse serum, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in mouse kidney were determined by kits; the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in mouse kidney were detected by ELISA kits; the pathological changes of the kidney were observed by hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining; and the expression of MMP9, GSK-3β, β-catenin, as well as Bcl-2 associated X-protein (Bax) and B-cell lymphoma-2 protein (Bcl-2) in renal tissue was verified by Western blot. The experimental results showed that the extract of Dracocephalum moldavica L. could significantly improve the organ indices of spleen, liver, and kidney in AKI mice; significantly reduce the levels of SCr and BUN in blood; reduce the levels of TNF-α, IL-6, and IL-1β; up-regulate the levels of GSH-PX and SOD; improve the pathological damage of kidney; and regulate the expression of MMP9, GSK-3β, β-catenin, Bax and Bcl-2 in renal tissue. It suggests that the extract of Dracocephalum moldavica L. may exert a protective effect on AKI caused by CDDP through regulating the expression of the GSK-3β/β-catenin signaling pathway.

Sarcopenia is an age-related progressive disease characterized by the loss of skeletal muscle mass and function, which seriously threatens the quality of life and survival of elderly individuals. Shiquandabu Decoction is a classical traditional Chinese herbal formula known for its effects in benefiting Qi and nourishing blood, and modern studies have demonstrated its potential therapeutic effects on sarcopenia. To investigate the protective effects and underlying mechanisms of Shiquandabu Decoction against sarcopenia, this study prepared its water decoction, administered it to rats by gavage, collected the drug-containing serum, and identified the components absorbed into the blood using UHPLC-Q-TOF-MS. The animal experiments in this study were conducted in compliance with the regulations of the Scientific Research Ethics Committee of Shanxi University of Chinese Medicine and approved by the Animal Experimentation Ethics Review (approval No.: AWE202403229). The drug-containing serum was used to treat a D-galactose (D-gal)-induced senescent C2C12 myotube model. CCK-8 was used to detect cell activity, DCFH-DA probe was used to detect reactive oxygen species (ROS) levels, JC-1 staining was used to detect mitochondrial membrane potential, flow cytometry was used to analyze the cell cycle, and RT-qPCR was used to detect the expression of myogenic differentiation-related factors (MyoD, MyoG, and Mstn) and senescence gene (p53). LC-MS proposed targeted metabolomics to screen for differential metabolites and analyze related pathways. The results showed that 15% drug-containing serum was able to significantly increase the cell survival rate, reduce the ROS levels, restore the mitochondrial membrane potential, reduce the G0/G1 phase cellular block, and promote the cell cycle process, and it was able to up-regulate the expression of MyoD and MyoG, and down-regulate the expression of Mstn and p53. Metabolomics studies of the proposed target cells showed that intervention with drug-containing serum resulted in the callback of 119 differential metabolites (42 up-regulated and 77 down-regulated), mainly related to amino acids, carbohydrates, lipids, nucleotides and energy metabolic pathways. These results suggest that the drug-containing serum of Shiquandabu Decoction exerts a protective effect against D-gal-induced myocyte attenuation through multi-target and multi-pathway synergistic effects, improving mitochondrial function, regulating the cell cycle and promoting myo-differentiation.

Phenolic and flavonoid glycosides have the multi-target regulatory advantages in anti-colitis. Using lactose and galactose as starting materials, five novel phenolic glycosides G-6a, G-6b, G-9, G-13 and G-Ⅱ-3a were synthesized through glycosylation, hydrolysis, reduction, and recrystallization. Using a mouse colitis model induced by dextran sulfate sodium, animal experiments have been approved by the Animal Ethics Committee of Ocean University of China (approval number: OUC-SMP-2024-06-05), the in vivo anti-colitis experiments showed that compound G-Ⅱ-3a exhibited significant anti-colitis effects at a daily dose of 25 mg·kg^-1, effectively inhibiting weight loss in mice, reducing disease activity index scores, alleviating colonic shortening, maintaining the integrity of colonic mucosal structure, and reducing inflammatory cell infiltration. Its anti-inflammatory effect is superior to mesalazine. G-Ⅱ-3a can inhibit the release of inflammatory factors IL-6, TNF-α, and NO from lipopolysaccharide induced mouse monocyte macrophages RAW264.7. Compound G-Ⅱ-3a is a potential lead compound for the treatment of inflammatory bowel disease.

A systematic study of the chemical constituents of the n-butanol extraction of Ephedra intermedia (E. intermedia) was carried out and 15 compounds were isolated using various column chromatography combinations with modern wave spectroscopy. Their structures were identified as (7R, 8S, 7′R, 8′S, 7″R, 8″S)-ephnan A (1), 4-methoxy garcimangosone D (2), garcimangosone D (3), (+)-syringaresinol (4), (+)-syringaresinol-O-β-D-glucopyranoside (5), methyl benzoate-4-β-glucoside (6), 3-methoxy-4-O-β-D-glucopyranosyloxy-benzoic acid methyl ester (7), methyl syringate 4-O-β-D-glucopyranoside (8), trans-4-O-β-D-glucopyranosyl ferulic acid (9), 3, 5-dimethoxy-4-O-β-D-glucopyranosyl-cinnamic acid (10), raspberry ketone O-β-D-glucopyranoside (11), E-melilotoside (12), β-D-glucopyranosyl-benzoate (13), 3, 4-dihydroxybenzoic acid 3-O-β-D-glucoside (14), 3, 5-dihydroxy-4-O-β-D-glucopyranosyl acetophenone (15). Compounds 1 and 2 were new compounds, compounds 6-9 and 13-15 were isolated from Ephedra for the first time. Compounds 7, 11-14 exhibited potential anti-pneumonia activity.

Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in children. 6-Mercaptopurine (6-MP) is a core chemotherapeutic drug for ALL, but its clinical application is limited by poor solubility, low biological availability, and significant side effects. To address these limitations and to investigate the impact of developmental differences between children and adults on drug absorption, this study developed 6-MP-loaded poly (lactic-co-glycolic acid) nanoparticles (6-MPNs) using a double emulsion-solvent evaporation method. We comprehensively applied high-performance liquid chromatography-mass spectrometry (HPLC-MS) and label-free quantitative proteomics, along with GO functional annotation via eggnog-mapper (v2.0) and protein-protein interaction analysis using STRING (v10.5), to systematically evaluate the pharmacokinetics, intestinal distribution, and duodenal protein expression differences of 6-MPNs in animal models of different ages. All animal studies were approved by the Animal Ethics Committee of Capital Medical University (Approval No.: AEEI-2020-072) and conducted in accordance with relevant guidelines. The results showed that 6-MPNs significantly improved the biological availability of 6-MP. Rats at 4 weeks of age group exhibited higher AUC_last (area under curve from time zero to time of last measurable concentration) and C_max (maximum concentration), faster intestinal absorption, more rapid propulsion, and higher transport efficiency from the intestinal epithelium to the portal vein compared to the rats at 16 weeks of age group. Proteomic analysis revealed that the rats at 16 weeks of age group had significantly lower expression of proteins related to fat digestion and transport, pancreatic secretion, membrane lipid metabolism, brush border recruitment, and microvillus adhesion. These findings suggest that the higher biological availability of 6-MPNs in younger animals may result from longer relative intestinal length, higher intestinal wall transport efficiency and more dynamic barrier construction.

Ultra-high performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) was applied for the non-targeted metabolomic characterization of Paeoniae Radix Alba and Paeoniae Radix Rubra decoction pieces. Differential metabolites were identified through multivariate statistical analysis. Interpretable machine learning methods, including random forest (RF), adaptive boosting (AdaBoost), and extreme gradient boosting (XGBoost), were further employed to build classification models, and the Shapley additive explanations (SHAP) algorithm was used to evaluate the contributions of characteristic metabolites. A total of 44 metabolites were identified, including 9 flavonoids, 8 phenolic acids, and other types of metabolites, among which 12 showed significant differences between the two kinds of decoction pieces. In the test set, the RF model exhibited superior performance. SHAP analysis indicated that gluconic acid, quercetin, kaempferol, L-aspartic acid, taxifolin, and oxypaeoniflorin significantly contributed to model discrimination, with L-aspartic acid showing elevated levels in Paeoniae Radix Alba, while the other metabolites were relatively higher in Paeoniae Radix Rubra. The metabonomics-machine learning strategy established in this study provides potential chemical evidence for elucidating the efficacy differences between Paeoniae Radix Alba and Paeoniae Radix Rubra and offers new insights into the identification, origin traceability, and characteristic marker discovery of other easily confused traditional Chinese medicines.

The study aims to establish a method for the content determination of eleven components in Jinchai Qingre Granule by high performance liquid chromatography-diode array detector (HPLC-DAD) through quantitative analysis of multi-components by single marker (QAMS) and verify the feasibility and applicability of the method in its quality control. Agilent ZORBAX SB-C18 column (250 mm × 4.6 mm, 5 μm) was used; acetonitrile-0.1% phosphoric acid aqueous solution was used as mobile phase; gradient elution and the detection wavelength were set at 327, 278, 250 nm; flow rate was 1.0 mL·min^-1; column temperature was 25 ℃. Using puerarin as the internal reference, the relative correction factors of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, daidzin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, baicalin, daidzein and arctiin was established, and the eleven components were determined. Eleventeen components showed good linear relationships within their own ranges (r ≥ 0.999 5), whose average recoveries were 98.05%-100.90% with the RSDs of 0.98%-2.35% (n = 6). The method showed good durability under different conditions such as instruments, columns, column temperature, injection volume, and flow rate. There was no significant difference between the calculated values of eleven components in ten batches of samples by the QAMS and the measured values of the external standard method (P > 0.05). The method established in the study is simple and stable, and can be used for the synchronous quality control of eleven index components in Jinchai Qingre Granule.

Interleukin-15 (IL-15) stimulates the proliferation of CD8⁺ T lymphocytes and activates cytotoxic T lymphocytes, memory CD8⁺ T cells, and natural killer cells, demonstrating broad application prospects in cancer immunotherapy. The activation of effector cells by IL-15 relies on a unique trans-presentation signaling mechanism. This process involves the initial binding of IL-15 to IL-15 receptor alpha (IL-15Rα) to form the IL-15/IL-15Rα complex, followed by binding of this complex to the IL-15 receptor beta/gamma (IL-15Rβ/γ) on target cells, thus exerting its pharmacological effects. The clinical application of recombinant interleukin-15 (rIL-15) faces challenges including its short half-life time and limited availability of endogenous IL-15 receptor alpha (IL-15Rα). Additionally, the immunosuppressive tumor microenvironment impairs its anti-tumor efficacy. In this study, a recombinant IL-15Rα-sushi-HSA fusion protein (rILR-HSA) is designed and expressed, which comprises the IL-15Rα sushi domain fused to human serum albumin (HSA). The co-hitchhiking drug delivery system, rILR-HSA/BPBBT/rIL-15 nanoparticles, prepared by the hydrophobic binding between the HSA component and the photothermal agent molecule BPBBT, followed by the high-affinity binding between IL-15Rα-sushi and rIL-15. Compared with free rIL-15, rILR-HSA/BPBBT/rIL-15 nanoparticles extend the serum half-life time of rIL-15 by 2.6-fold. Simultaneously, the tumor accumulation of rILR-HSA/BPBBT/rIL-15 nanoparticles in the orthotopic CT26-Luc colon cancer-bearing mice facilitates intraoperative near-infrared window-Ⅱ fluorescence image-guided photothermal immunotherapy. The co-hitchhiking drug delivery strategy employs a fusion protein carrier to co-deliver rIL-15 and photothermal agent, providing an approach for safe and effective IL-15-based photothermal immunotherapy of tumor. Animal experiments were conducted with the approval of the Institutional Animal Care and Use Committee of the School of Pharmacy, Fudan University (ethics number: 2018-09-YJ-LW-01).

Volatile oil of traditional Chinese medicine (TCM) is an important intermediate in TCM preparations. However, its strong volatility and poor stability hinder the stable application of solid preparations containing volatile oil. There is an urgent need to develop novel stabilization and sustained/controlled-release technologies. In this study, four porous materials, namely SiO₂, Sylysia 350FCP silica (350FCP-SiO₂), Sylysia 770FCP silica (770FCP-SiO₂), and porous starch, were used to prepare solidified powder of the volatile oil of Chenxiang and Muxiang (CMVO). Comprehensive characterization of the solidified powder was conducted using scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), simultaneous thermal analysis, and electronic nose methods. The pore size, pore characteristics of the materials, and the release behavior of the components before and after solidification of the volatile oil were analyzed to evaluate its sustained-release performance. Finally, multivariate statistical analysis methods were used to evaluate the correlation between the key physicochemical parameters of the carrier materials and the adsorption rate of the essential oil, as well as the sustained/controlled-release performance of the components. The results showed that among the four carriers, 350FCP-SiO₂ exhibited the strongest adsorption capacity for the essential oil, with an adsorption ratio of essential oil to carrier as high as 2.5 mL·g^-1. In terms of sustained-release performance, 350FCP-SiO₂ and 770FCP-SiO₂ exhibited a sustained-release effect on benzylacetone, a strongly volatile component in CMVO. Correlation analysis indicated that the adsorption rate of the material was positively correlated with the BJH cumulative adsorption volume and the total single-point adsorption pore volume. The 24-hour retention rate of benzylacetone was mainly positively correlated with the t-plot micropore volume and t-plot micropore area of the material, while dehydrocostus lactone, a weakly volatile component, was less affected by the carrier material during its release process. This study demonstrates that porous materials with different physicochemical properties and pore characteristics can effectively regulate the sustained-release performance of different volatile components in TCM essential oils. The findings provide theoretical basis and application reference for the solidification and stabilization of TCM essential oils.

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder characterised by gut dysbiosis and redox imbalance. This study developed a novel oral micro-nano delivery system (CBs@BAN) based on Clostridium butyricum spores (CBs) and bilirubin-alginate nanoparticles (BAN). Amino-modified bilirubin (BR) was first covalently conjugated with sodium alginate (Alg) to prepare amphiphilic block BR-Alg, which subsequently self-assembled into BAN nanoparticles with a particle size of 163.52 ± 2.71 nm and a zeta potential of -43.2 ± 1.6 mV. These nanoparticles were efficiently loaded onto the surface of CBs via calcium ion cross-linking. In vitro experiments demonstrated that BAN exhibits potent reactive oxygen species (ROS) scavenging capacity, while CBs@BAN maintained spore germination activity. Following review and approval by the Animal Ethics Committee of Zhengzhou University (approval number: yxy11sc20250099), a murine colitis model was induced using 3% dextran sulfate sodium (DSS). Compared with other experimental groups, CBs@BAN demonstrated superior therapeutic efficacy, including accelerated body weight recovery, reduced disease activity index (DAI) scores, ameliorated histopathological damage in colon tissue, effective clearance of colonic ROS, suppression of inflammatory cytokine expression, and improved gut microbiota imbalance. By restoring redox homeostasis and modulating gut microbiota, this delivery system provides a novel and efficient solution for IBD treatment with promising application potential.

Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease of unknown etiology with limited therapeutic options. Bioinformatics enrichment analysis indicates that oxidative stress and metabolic dysregulation of alveolar epithelial type II cells (AECs II) may contribute to PF pathogenesis. With recent advances in molecular biology and genetic engineering, gene therapy has emerged as a promising therapeutic strategy for PF. However, its clinical translation remains challenging due to biological barriers that hinders efficient delivery of therapeutic genes. To address this limitation, we explored main factors affecting transfection efficiency and screened optimal prescription to develop nanocomplexes (NPs@pSIRT3) via delivery of sirtuin 3 plasmid (pSIRT3) to treat PF. The NPs@pSIRT3 exhibited superior transfection efficiency, mediating robust SIRT3 protein expression to achieve therapeutic efficacy. Comparative analysis with excipient-deficient control groups demonstrated that the optimized nanoparticles (NPs) effectively delivered therapeutic genes to fibrotic lesions, enhancing pSIRT3 transfection. The NPs@pSIRT3 significantly attenuated PF progression by modulating oxidative stress normalization of injured AECs II, anti-inflammatory effects, and finally inhibition of pro-fibrotic responses. These findings demonstrate that the engineered NPs@pSIRT3 system represents a promising gene delivery platform for PF therapy, and providing a novel strategy for efficient transfection of gene therapy. All animal procedures were performed in accordance with the guidelines of and approved by the Institutional Animal Care and Use Committee of Jinzhou Medical University (approval number: 240134-5).

Epidemiology shows that alopecia afflicts about half of the adult population worldwide and has become an important health problem affecting the daily lives of the general public. Due to the complexity of the etiology alopecia and the limited number of available treatments, it is important to develop efficient and safe treatment options. In this study, dutasteride (DUT) nanovesicles (NV@DUT) with egg yolk lecithin, oleic acid and vitamin E polyethylene glycol succinate were constructed, aiming to enhance the skin penetration and retention of DUT while having multiple coordinated effects of antioxidation and anti-inflammation, thereby improving the therapeutic effect. NV@DUT has a slightly milky luster, with a particle size of about 141.3 ± 0.45 nm, uniformly dispersed, its polydispersity index (PDI) is 0.17 ± 0.003. After 60 days of placement at room temperature with small changes in particle size and PDI. Compared with free DUT, the transdermal penetration and skin retention of the drug in NV@DUT increased by approximately 1.7 times. In vitro results showed that NV@DUT has antioxidant and anti-inflammatory activity. At 500 μg·mL^-1 NV@DUT, the scavenging rate of radicals was about 50%, and the inhibition rate of nitric oxide production was about 50%, it improves the homeostasis of the hair follicle microenvironment. In addition, at 20 μg·mL^-1 NV@DUT can promote the proliferation and migration of dermal papilla cells (HDPCs) and human umbilical vein endothelial cells (HUVECs), the cell viability were (132.67 ± 4.14)% and (116.64 ± 5.14)%; the migration rates were (84.68 ± 3.31)% and (61.87 ± 4.23)%. A preliminary investigation of its mechanism revealed that NV@DUT up-regulate the mRNA expression of β-catenin, vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and down-regulation the mRNA expression of type II 5 alpha-reductase (SRD5A2). NV@DUT can also promote hair regrowth in mice with androgenetic alopecia (AGA), and the weight of the new hair and the thickness of the skin in the mice were higher than those in the model group and the DUT group. The animal experiments were approved by the Laboratory Animal Ethics Committee of Sun Yat-Sen University, and all experiments were conducted in accordance with relevant guidelines and regulations. Approval number: 2022000828. The experimental results show that NV@DUT can treat AGA through multiple mechanisms and pathways, providing a new therapeutic strategy for alopecia.

Manganese dioxide (MnO₂), as an intelligent drug carrier responsive to the tumor microenvironment (tumor microenvironment, TME), has recently garnered significant attention due to its unique physicochemical properties. However, the low specific surface area of conventional MnO₂ materials severely limits their drug-loading capacity. In this study, three-dimensional urchin-like MnO₂ nanomaterials were successfully synthesized through an optimized hydrothermal process, and a composite MnO₂/Au nanoparticles (GNPs) system was constructed by immobilizing Au NPs onto the MnO₂ surface via an impregnation method. Structural characterization revealed that the as-prepared urchin-like MnO₂ exhibits a distinctive hollow-radial architecture with a specific surface area of 35.75 m²·g^-1, significantly higher than that of conventional MnO₂ materials (14-30 m²·g^-1). Under near-infrared laser irradiation (808 nm, 2.5 W·cm^-2), the composite demonstrated exceptional photothermal performance, achieving a temperature rise to 55 ℃ within 5 minutes and a calculated photothermal conversion efficiency of 61.85%. Drug-loading evaluations indicated a high loading efficiency of 81.3% for 5-fluorouracil, along with pH-responsive release characteristics, achieving 86.4% cumulative drug release within 2 h under simulated TME conditions (pH 5.0). By integrating morphology engineering and noble metal hybridization strategies, this work establishes a multifunctional nano-platform that combines high drug-loading capacity, controllable release, and efficient photothermal conversion, providing critical theoretical and technical foundations for developing synergistic chemo-photothermal therapeutic systems.

The treatment of gliomas faces significant challenges due to limitations imposed by the blood-brain barrier and the immunosuppressive tumor microenvironment. This study developed a perillyl alcohol-based nanoemulsion (POH-NE), which utilizes the reversible BBB-opening property of POH to efficiently deliver the STING agonist MSA-2 into the brain, aiming to achieve synergistic immunomodulation and antitumor therapy. ^MSA-2POH-NE exhibits uniform particle size (87.6 ± 2.3 nm) and neutral surface charge (-0.17 ± 0.1 mV), demonstrating system stability. In vivo distribution experiments demonstrated that POH-NE increased drug accumulation in the brain to 4.6 times that of conventional nanoemulsions. Mechanistic studies revealed that POH-NE reversibly reduced transendothelial electrical resistance and downregulated the expression of tight junction proteins Claudin-5 and ZO-1, while exerting no significant effect on the non-tight junction protein CD31. This suggests that POH may facilitate controllable BBB opening through coordinated paracellular and transcellular pathways. In an orthotopic glioma model, ^MSA-2POH-NE significantly activated the STING signaling pathway, promoted type I interferon production, enhanced the infiltration and activation of dendritic cells and cytotoxic T lymphocytes within tumors, and cooperatively reversed the immunosuppressive microenvironment. All animal experiments had been approved by the Experimental Animal Ethics Committee of the Institute of Laboratory Animals Science, Chinese Academy of Medical Sciences (No: SXD23001). In conclusion, this study proposed a novel combinatorial strategy for glioma immunotherapy based on reversible BBB opening and STING pathway activation, providing an experimental foundation for subsequent translational research.

Calcium-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.