In 2024, drug discovery continues to develop on the basis of the achievement before. The number of approved first-in-class (FIC) drugs reach a higher level. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 50 novel drugs, including 30 small molecule drugs and 20 macromolecule drugs. Comparing to the number of approved drugs in 2023, the total in 2024 falls slightly. But the proportion of FIC drugs increase obviously. There are 24 FIC drugs (48%) approved in 2024, which include 13 FIC small molecule drugs and 11 FIC macromolecule drugs and whose indications mainly focus on tumor, and endocrine and metabolic disease. Among 24 FIC drugs, many drugs have breakthrough clinical value, such as the first combination of muscarinic acetylcholine receptor M1/M4 agonist and peripheral muscarinic acetylcholine receptor antagonist, xanomeline and trospium chloride, the first thyroid hormone receptor beta agonist, resmetirom, the first dual antagonist of endothelin receptor type A and B to treat hypertension, aprocitentan. The huge value of FIC drugs in clinical therapy, academic research and commerce, is attracting wide attention from the patients, researchers and enterprises. This review will analyze the research background, development process and therapeutic application of three first-in-class small molecule drugs in this year from a medicinal chemistry perspective, expecting to provide more research directions and methods for the development and research of FIC drugs.

Exosomes are small vesicles secreted by cells that contain important bioactive molecules such as nucleic acids and proteins. Increasing research indicates that exosomes play a unique and crucial role as signal molecule carriers in various diseases, and they exhibit great potential in disease diagnosis and treatment. Recent studies have shown that exosomes play an important role in immune regulation. The NOD (nucleotide binding oligomerization domain)-like receptors protein 3 (NLRP3), an essential component of the innate immune system, plays a key role in the occurrence and development of various diseases including autoimmune diseases, metabolic diseases, and neurodegenerative diseases. Its activation and regulatory mechanisms are complex and diverse. However, the regulatory mechanisms associated with exosomes and NLRP3 inflammasome have not yet been fully elucidated. This article reviews the regulatory effects of exosomes from different sources on the NLRP3 inflammasome and summarizes the therapeutic potential of exosomes in diseases associated with the NLRP3 inflammasome, aiming to provide new ideas for the prevention and treatment of diseases related to the NLRP3 inflammasome.

Radiopharmaceuticals play a crucial role in nuclear medicine, with the development of radioligands being a key focus in this field. Peptide-based radiopharmaceuticals have shown significant advantages in clinical applications, with the majority of FDA-approved targeting radiopharmaceuticals since 2018 being derived from peptides or peptidomimetics. Bicyclic peptides have emerged as a promising targeting moiety in radioligands, offering improved biophysical properties compared to linear or monocyclic peptide ligands. This article provides an overview of the methods for obtaining bicyclic peptide ligands, as well as highlighting the major clinical and preclinical advancements in bicyclic peptide-based radiopharmaceuticals. The review also discusses the future prospects of bicyclic peptide-based radiopharmaceuticals, offering insights for practitioners in the field of pharmaceutical science and nuclear medicine to keep up with the latest developments in radiopharmaceutical innovation.

Respiratory infections, as common diseases, along with other respiratory system diseases such as asthma, rare diseases including cystic fibrosis, chronic obstructive pulmonary disease, and lung cancer, can be prevented using vaccines. Taking respiratory infections as an example, vaccines are mostly administered via intramuscular injection, inducing the production of serum IgG, thereby neutralizing viral infectivity and alleviating COVID-19 symptoms. However, due to the lack of secretory IgA and IgG in muscle tissues, intramuscular vaccines cannot quickly provide protection to the respiratory tract. To overcome the shortcomings of intramuscular injection, some vaccine candidates for nasal or nebulized inhalation are under development or have been approved. Clinical studies show that inhaled vaccines can induce antibody responses similar to those of intramuscular vaccines at much lower doses. Inhaled vaccines can simultaneously induce humoral, cellular, and mucosal immunity, providing triple protection. With the application of new vaccines (e.g. mRNA vaccines and DNA vaccines) in inhalable formulations for COVID-19, inhaled vaccines have been proven to have broad application prospects in the prevention of lung diseases. Given this background and the known abundance of immune cells in the lungs, increasing research efforts are devoted to developing single-dose inhalable nano dry powder vaccines. This article discusses the roles and advantages of inhaled vaccines in mucosal immunity, their potentials for treating different diseases, and prospects for the future development of inhaled vaccines based on nanotechnology.

Human influenza is mainly caused by influenza A virus and influenza B virus, and it is one of the most serious infectious diseases that pose a serious threat to human health. Currently, there are few marketed drugs for influenza viruses, and the existing drugs are faced with problems such as drug resistance. The development and research of combinations of anti-influenza drugs have gradually attracted people's attention. At present, certain progress has been made in aspects such as the discovery of anti-influenza drug combinations and the evaluation of drug effects. Discovering effective combination drugs is an ideal method for repurposing old drugs. That can be used to improve therapeutic effects and delay or reduce the occurrence of drug resistance. Herein, this article introduces the evaluation methods, models of combinations of anti-influenza drugs, as well as available data resources and tools, and summarizes the latest progress in the current research on combinations of anti-influenza drugs, with the aim of providing a reference for the research and development of the combined application of anti-influenza virus drugs.

Human cytomegalovirus (HCMV) infection poses significant morbidity and/or mortality risks for individuals with compromised immune systems, rendering it one of the most prevalent congenital infections worldwide. The pursuit of HCMV vaccines has spanned over five decades, with clinical trials primarily focusing on various vaccine candidates, including live attenuated vaccines, viral vectored vaccines, subunit vaccines, peptide vaccines, DNA vaccines, RNA vaccines, and viral-like particle vaccines, usually accompanied by the use of adjuvants. Although the development of vaccines against HCMV is being actively promoted, there are still numerous obstacles and challenges persisting in the research process, due to unique pathogenic characteristics and infection mechanisms of HCMV. Based on the summarized research progress, this article analyzes and discusses the faced challenges and potential approaches to provide valuable insights and guidance for the exploration and development of new vaccines candidates, and ultimately achieve prevention and control of HCMV infection.

Immune checkpoint inhibitors (ICIs) have emerged as critical agents in cancer immunotherapy; however, their resistance and limited response in most patients pose significant challenge. The gut microbiota, as a pivotal immune regulator, has been increasingly recognized for its role in enhancing the therapeutic efficacy of ICIs. Studies demonstrate that fecal microbiota transplantation or transplantation of specific bacterial strains can directly reshape the gut microbiota composition, thereby improving ICI therapeutic outcomes. Furthermore, dietary interventions, prebiotics, and postbiotics have shown potential in augmenting the anti-tumor effects of ICIs through gut microbiota modulation. Despite these promising findings, further investigations are required to optimize microbiota-based strategies and therapeutic protocols. This review highlights the critical role of gut microbiota modulation in ICI-based cancer therapy and explores its clinical applications, offering both practical insights and theoretical foundations for improving immunotherapy outcomes against various cancers.

There are abundant resources of traditional Chinese medicine in China, and it is found that the effective components of traditional Chinese medicine contain functional groups that are easy to coordinate with metal ions, such as amino, carboxyl and hydroxyl, which can complex with transition metal ions to derive new compounds. These traditional Chinese medicine metal complexes often exhibit unique properties and functions compared with their corresponding monomers, providing a new path for new drug development. Based on the formation principle of metal complexes with traditional Chinese medicine and the common coordination metal ions, in this review, the effective components in traditional Chinese medicine are roughly divided into anthraquinone, alkaloid, flavone, coumarin, amino acids and polysaccharide compounds, so as to provide new ideas for the discovery of new traditional Chinese medicine, and provide scientific basis for the modernization and internationalization of traditional Chinese medicine.

Gliomas are the most common primary tumors in the central nervous system. However, the efficacy of first-line treatments for glioma is hindered by the blood brain barrier (BBB), making it difficult to reach an effective dose at the tumor site. The volatile oil from traditional Chinese medicine have the advantages of high fat solubility and ability to penetrate the blood brain barrier, has demonstrated promising inhibitory effects on glioma. The volatile oil components of traditional Chinese medicine can improve the anti-glioma efficacy by promoting the entry of chemotherapeutic drugs into the brain, inhibiting the exocytosis of drugs within the brain and synergizing with chemical drug therapy. However, the stability of volatile oil is poor, nano-formulations including liposomes, nanoparticles, and self-assembled prodrug delivery systems, can improve their stability and exert the therapeutic efficacy. As an effective drug for the treatment of glioma, volatile oil from traditional Chinese medicine shows good prospects for application. This review summarizes the mechanisms of action of volatile oil from traditional Chinese medicine and their main components against glioma, and the research progress of volatile oil combined with chemotherapeutic drugs or designed as nano-drug delivery systems for glioma therapy, with a view to providing reference for the application of volatile oil from traditional Chinese medicine in the treatment of glioma.

Vaccines are often administered by intramuscular or subcutaneous injection. Although these methods can effectively deliver vaccine antigens to the body and trigger the immune response. However, there are also some limitations, such as injection pain, complex operation, strict transportation conditions, poor immunogenicity and stability of the vaccine. With the development of technology, skin administration has become another new way to solve the above-mentioned problems of vaccine. Among the many ways of skin administration, microneedles show unique advantages and potential. This paper briefly describes the mechanism of microneedle transdermal immunity and its advantages over traditional injection. This paper briefly describes the mechanism and advantages of transdermal immunity of microneedles, enumerates the classification of microneedles, focuses on the design concept, structural advantages and preparation technology of bionic microneedles, and analyzes its application potential in vaccines. At the same time, this paper briefly describes the application of microneedle in vaccine, including bacterial infection, viral infection, cancer treatment and current clinical application progress. The challenges and prospects of microneedle vaccine are summarized from the aspects of safety, stability and acceptability of microneedle vaccine.

Conjugated estrogens (CE) are widely used in menopausal hormone therapy (MHT) for the relief of menopause-related symptoms (e.g., vasodilatory symptoms, neuropsychiatric symptoms, genitourinary atrophy symptoms, etc.) and the prevention of postmenopausal osteoporosis. This article reviews the characteristics, pharmacological effects, and practical applications of different dosage forms of CE (tablets, creams, and injections) in clinical practice. It has been shown that tablet CE effectively regulates the body's temperature center through systemic treatment, reduces hot flashes and night sweats, promotes bone formation, and increases bone density. Cream CE is used for local treatment to improve the genitourinary syndrome of menopause (GSM). Injectable CE is used for the treatment of abnormal uterine bleeding caused by hormonal imbalance without organ pathology. CE administered intravenously is indicated only for short-term use to rapidly and temporarily increase estrogen levels. Additionally, CE plays an important role in metabolism by improving insulin clearance and sensitivity and potentially protecting the nervous and cardiovascular systems, demonstrating a wide range of therapeutic potential. This paper provides new ideas for the design and development of drug dosage forms by exploring the formulation and application of CE.

Through literature analysis, the advantages of oral pharmaceutical vehicles in solving the temporary dispensing problems for special populations are summarized. Detailed introduction is made on the research, development, production, use, and regulatory experience of oral pharmaceutical vehicles in the United States, as well as the current research progress, achievements, and challenges faced by domestic oral pharmaceutical vehicles. The United States has formed a mature system in the field of oral pharmaceutical vehicles, and China can learn from the experience of the United States to improve relevant laws and policies, promote the establishment of technical guidance principles and technical standards for the use of oral pharmaceutical vehicles in temporary dispensing, and accelerate its clinical use.

Indigo naturalis [Baphicacanthus cusia (Nees) Bremek., QD], as a traditional Chinese medicine, has exhibited efficacy in the ulcerative colitis (UC). Cu Dian (CD), the current form of Indigo naturalis, has been regarded as the mainstream form of medicine today. Dian Hua (DH) is the traditional purified form of QD, in which the content of indigo and indirubin is higher than that of CD. The study evaluated the efficacy of DH and CD in UC and explored their mechanism. Male BALB/c mice were subjected to an 8-day regimen of 3% dextran sodium sulphate (DSS) drinking water to induce UC. The experiment was approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (approval number: 2024075). Concurrently, the mice received intragastric administration of CD (400, 200, and 100 mg·kg^-1) and DH (400, 200, 100, and 50 mg·kg^-1) for the same duration. The anti-inflammatory properties of CD and DH were evaluated by quantifying levels of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18 in colon tissue. Western blot and immunofluorescence assays were employed to assess the protein levels of zonula occludens 1 (ZO-1) and occludin. Additionally, Western blot and RT-qPCR were utilized to analyze the protein and gene expression levels of AMP-activated protein kinase (AMPK), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), and related factors in colon tissue. CD and DH demonstrated a capacity to alleviate inflammatory responses in mice with UC. The protective impact of both CD and DH on the intestinal mucosal barrier was associated with an elevation of ZO-1 and occludin. Furthermore, the anti-inflammatory effects of CD and DH were attributed to the inhibition of the NLRP3 inflammasome through the activation of the AMPK/silent information regulator of transcription 1 (SIRT1) pathway. Notably, DH exhibited a more pronounced improvement in UC compared to CD, particularly at the dosage of DH-M (200 mg·kg^-1). Our investigation substantiates the effectiveness of CD and DH in mitigating DSS-induced UC in mice. They demonstrated a capacity to diminish the production of inflammatory cytokines and safeguard the integrity of the intestinal epithelial barrier, notably by elevating level of tight junctions. The anti-colonic inflammatory effects of CD and DH were elucidated through the inhibition of both the formation and activation of the NLRP3 inflammasome, mediated by the AMPK/SIRT1 pathway.

To investigate the effect and underlying mechanism of action of Yueju volatile oil (YJVO) in the treatment of high altitude sleep disturbance (HASD) mice, gas chromatography-mass spectrometry (GC-MS) was used to identify the components of YJVO, while network pharmacology was applied to predict the mechanism of action. KM mice were selected and randomly assigned to several groups: the control group (control), the model group (model), and the YJVO treatment groups at low (YJVO-L, 200 μL·m^-3), medium (YJVO-M, 400 μL·m^-3), and high (YJVO-H, 800 μL·m^-3) doses, as well as the diazepam group (DZP, 2 mg·kg^-1). Except for the control group, all mice were subjected to a hypobaric oxygen chamber to establish the HASD model. Animal experiments were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics No.: TEMPOR20230088). Co-sleeping and weight-bearing swimming experiments were conducted to assess the sleep-regulating effects of YJVO. Hematoxylin and eosin (H&E) staining was employed to observe damage in hypothalamic and hippocampal brain tissues. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure levels of melatonin (MT), γ-aminobutyric acid (GABA), interleukin-6 (IL-6), interleukin-1beta (IL-1β), 5-hydroxytryptamine (5-HT), orexin-A, and tumor necrosis factor-α (TNF-α) in both plasma and brain tissues. Concurrently, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) were detected to evaluate oxidative stress. Western blot was used to determine the expression of key proteins in the NF-κB/NLRP3 pathway, and immunohistochemistry (IHC) was used to detect the expression of 5-hydroxytryptamine 1A receptor (5-HT_1A) in hippocampal and hypothalamic tissues. The GC-MS results revealed that YJVO was identified to contain 68 components. Network pharmacology results indicated that the mechanism of YJVO in treating HASD involves multiple signaling pathways such as AGE-RAGE, TNF, serotonin, and NF-κB. Behavioral experiments indicated that YJVO significantly prolonged the sleep duration, reduced the sleep latency, and bolstered the physical endurance and anti-fatigue capabilities of mice (P < 0.01). H&E staining results showed significant improvement in the pathological damage of the hippocampus and hypothalamus tissues in HASD mice. ELISA results indicated that YJVO increased the concentrations of sleep-inducing neurotransmitters MT and GABA within brain tissues, decreased the levels of wakefulness-inducing neurotransmitters orexin-A and 5-HT in plasma, and attenuated the secretion of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α (P < 0.01). Biochemical results indicated that YJVO could inhibit the production of MDA in the brain tissue of HASD mice and enhance the activity of SOD and GSH-PX (P < 0.01). Western blot results showed that YJVO downregulated the protein expression of phosphorylate nuclear factor-kappa B (p-NF-κB p65)/nuclear factor-kappa B (NF-κB p65), Nod-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (Caspase-1), and IL-1β in the brain tissue of HASD mice (P < 0.01). IHC results demonstrated that YJVO downregulated the protein expression of 5-HT_1A in the hippocampus and hypothalamus tissues of HASD mice (P < 0.01). The study findings indicate that YJVO demonstrates potent therapeutic effects in HASD mice, potentially through the modulation of neurotransmitters and the attenuation of neuroinflammation.

This study investigates the anti-fatigue effects and mechanisms of Lycium barbarum and Ginseng combination using network pharmacology and in vivo validation. The effective components and their action targets of Lycium barbarum and Ginseng were explored through TCMSP, ETCM and other databases combined with literature. The fatigue targets were obtained through OMIM and Gene Cards databases. The intersection targets of drug targets and disease targets were screened out and imported into String database and Cytoscape 3.10.0 to construct PPI network. GO and KEGG enrichment analysis of the core targets were performed by David database. A mouse exercise-induced fatigue model was established to evaluate the anti-fatigue effects and mechanisms of the Lycium barbarum-Ginseng combination. The results showed that 55 active ingredients of Lycium barbarum and Ginseng were obtained, corresponding to 573 targets. The number of fatigue targets was 1 137, 115 total targets and 26 core targets were screened. KEGG enrichment pathways mainly included PI3K-AKT, HIF-1α, AGE-RAGE and other signaling pathways. All animal experiments were approved by the Experimental Animal Ethics Committee of Nanjing University of Chinese Medicine (approval number: 202308A018). The results showed that the low, middle and high dose groups of Lycium barbarum and Ginseng (1∶1) could prolong the exhaustive swimming time of mice, and the middle dose group had a more significant effect than Ginseng group and Lycium barbarum group. The middle and high dose groups of Lycium barbarum combined with Ginseng significantly reduced blood urea nitrogen (BUN) in mice. Compared with Ginseng group and Lycium barbarum group, the high dose group had a more significant effect. Lactic acid (LD) levels were significantly decreased in Ginseng group, Lycium barbarum group and combination group. Compared with the Ginseng group, the levels of liver glycogen (Lgly) and muscle glycogen (Mgly) were significantly increased in the middle dose group of Lycium barbarum combined with Ginseng. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were significantly decreased in Ginseng group and Lycium barbarum combined with Ginseng high dose group. The content of glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) in the high dose group of Lycium barbarum combined with Ginseng can be significantly decreased. The results of Western blot showed that the low dose group of Lycium barbarum combined with Ginseng could significantly up-regulate the expression of P-PI3K and AKT proteins in the muscle tissue of fatigue mice, and the middle dose group could significantly down-regulate the expression of P-AKT and HIF-1α proteins. Compared with Ginseng group and Lycium barbarum group, the expression of PI3K protein in the high dose group was significantly increased. The expression of AKT protein in the low-dose group was significantly increased. In conclusion, Lycium barbarum combined with Ginseng has more positive effects on improving exercise endurance, reducing the accumulation of metabolites and improving glycogen storage levels in mice than Ginseng group and Lycium barbarum group, and its mechanism may be the regulation of AKT, PI3K, HIF-1α and other core targets and PI3K/AKT/HIF-1α signaling pathway to exert anti-fatigue effect.

Liver fibrosis is a common stage in the progression of chronic liver diseases, yet there is a lack of clinical drugs against liver fibrosis globally. Gynostemma pentaphyllum has the name of "Southern ginseng", commonly used in folk prevention and treatment of a variety of chronic liver disease, there are also reports of its anti-hepatic fibrosis. However, there are fewer relevant scientific studies. In this study, we used LC-MS metabolomics analysis to investigate the effects of Gynostemma pentaphyllum ethanol extract (GPE) on liver fibrosis in carbon tetrachloride (CCl₄)-induced mouse models and its potential mechanisms. All animal experiments were approved by the experimental animal ethics committee of Capital Medical University (DWLLGZR202202204). The results showed that GPE could significantly reduce the inflammatory cell infiltration and collagen accumulation in the liver of model mice, significantly reduce serum alanine transaminase and aspartate transaminase activity and hypoxanthine levels in mice, and could effectively inhibit the gene transcription and protein expression of collagen 1A1 (COL 1A1) and α-smooth muscle actin (α-SMA). Non-targeted metabolomics analysis of the liver showed that GPE mainly affected 47 differential metabolites; KEGG pathway enrichment analysis indicated that the differential metabolites were mainly enriched in the fructose/mannose metabolism and aromatic amino acid metabolism pathways. The targeted metabolomic assay was further used to validate a total of 13 differential metabolites of D-mannose, mannose 6-phosphate, D-fructose, fructose 2-phosphate, D-sucrose, trehalose, glutamate, phenylalanine, tyrosine, L-2-amino-3-oxobutyric acid, lactate, 2-hydroxybutyrate, and taurine, which may be important metabolites related to GPE's anti-fibrotic effects. This confirms that GPE's anti-liver fibrosis effects may be closely related to the regulation of the fructose/mannose metabolism pathway and the aromatic amino acid metabolism pathway.

To establish the cells stably co-expressing NOD1 receptor and enhanced green fluorescent protein (EGFP)-tagged nuclear factor of activated T cells 2 nuclear factor (NFAT2) (EGFP-NFAT2) in U2OS cell, the NOD1 (NM_006092) pcDNA3.1-3×Flag-hygro recombinant plasmid was transfected into U2OS-EGFP-NFAT2 cells, which were screened by pressure of hygromycin B and then incubated with NOD1 agonist lipopolysaccharides (LPS) for 30 min, and the green fluorescence intensity in the nucleus of the cells was detected by the high content screening assay. There were 46 cell strains expressing NOD1 in U2OS-EGFP-NFAT2 cells by EGFP-NFAT2 nuclear translocation assay. Among these cells, cells No 4 had the highest nuclear translocation function. Therefore, it was selected as the U2OS-EGFP-NFAT2-NOD1 cell for functional validation. The expression levels of NOD1 mRNA and protein in the selected U2OS-EGFP-NFAT2-NOD1 cells and the control cell U2OS-EGFP-NFAT2 were examined by real-time quantitative PCR (RT-qPCR) and Western blot. The results showed that NOD1 mRNA was stably expressed in this stably transfected cell line for 5-20 generations, and NOD1 protein was expressed in U2OS-EGFP-NFAT2-NOD1 stably transfected cell line, whereas no NOD1 protein was expressed in the control cell U2OS-EGFP-NFAT2. U2OS-EGFP-NFAT2-NOD1 cells were treated with histones or LPS for 30 min, and the EGFP-NFAT2 nuclear translocation was detected by the high content screening assay. Histones were found to significantly increase the EGFP-NFAT2 nuclear translocation in U2OS-EGFP-NFAT2-NOD1 stably transfected cells over a range of concentrations. The U2OS-EGFP-NFAT2-NOD1 cells were divided into the solvent control group, NOD1 receptor antagonist nodinitib-1+histone group, and histone group. The drug incubation time was 30 min, and the specificity of the NOD1 cells was verified by observing the EGFP-NFAT2 nuclear translocation through the high content screening assay. Compared with the histones group, the nodinitib-1+histones group significantly decreased EGFP-NFAT2 nuclear translocation in U2OSEGFP-NFAT2-NOD1 cells (P < 0.05). In conclusion, U2OS-EGFP-NFAT2-NOD1 cells stably co-expressing NOD1 and EGFP-NFAT2 are established, which can be used for screening antagonistic compounds targeting NOD1 pathogenic microorganisms with mechanism study.

Yeast-derived microcapsules were employed to co-encapsulate a nano-emulsion adjuvant (MF59) and antigens, effectively addressing the limitations of MF59 adjuvant in direct antigen encapsulation and its capacity to induce cellular immunity. Yeast microcapsules (YCs) were prepared using strong acid and alkali treatments, resulting in a porous and hollow structure with enhanced adjuvant properties. Positively charged polycaprolactone-polyethyleneimine (PCL-PEI) modified MF59 nanoemulsions were produced, which allowed for electrostatic interaction-driven spontaneous deposition into YCs. This modification facilitated the adsorption of the antigen, chicken ovalbumin (OVA), forming the complex YC-MF59-OVA. YC-MF59-OVA was efficiently recognized and endocytosed by antigen-presenting cells (APCs), a process facilitated by the β-glucan present on the capsular shell. Simultaneously, YC-MF59-OVA enabled a sustained release of the antigen and promoted the recruitment of APCs at the site of inoculation, leading to enhanced activation of immune responses in mice. Specifically, YC-MF59-OVA significantly elevated serum levels of IgG, IgG1, and IgG2a antibodies, achieving concentrations that were two to three times higher than those observed in the group treated with free OVA. In addition, the cellular immune response was notably improved, as evidenced by increased frequencies of IFN-γ⁺CD8⁺ and IL-4⁺CD4⁺ T cells compared to the OVA-immunized group. Furthermore, there was a marked increase in the proportion of memory T cells (CD44⁺CD62L⁺) in the splenic tissues of treated animals. The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Zunyi Medical University (approval No. ZMU21-2407-169). These findings demonstrate that YC-MF59-OVA can elicit robust humoral and cellular immune responses, confirming that YC can significantly overcome the limitations of traditional nanoemulsion adjuvants. This study provides a promising reference for the development of advanced vaccine delivery systems.

Severe alcoholic hepatitis (SAH) represents the most extreme form of alcoholic liver disease (ALD), accompanied by an extremely high mortality rate. Currently, there is a dearth of appropriate animal models for related research. The objective of this study is to establish a mouse model of SAH, thereby providing a preclinical animal model for subsequent research on SAH. This study is based on the NIAAA (National Institute on Alcohol Abuse and Alcoholism) model and constructs a mouse model by combining bacterial endotoxins. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-102). The model emulates the pathological processes of clinical SAH in terms of mouse mortality, liver tissue damage, and inflammatory markers, thereby establishing the model. Ultimately, it is ascertained that the optimal conditions for SAH mouse modeling based on the NIAAA model are the last intragastric administration of alcohol at a concentration of 7.5 g·kg^-1 in combination with intraperitoneal injection of lipopolysaccharide at a dose of 5 mg·kg^-1 for a period of 12 h. Under these conditions, the mouse model effectively simulates the high mortality and liver dysfunction seen in clinical SAH, with pathological staining results closely mirroring clinical findings. Additionally, it demonstrates a significant infiltration of neutrophils in the liver, indicative of an excessive inflammatory response. This model provides an ideal platform for preclinical research on SAH.

Five sesquiterpenoids were isolated from a 50% acetone extract of Cornus officinalis leaves, a traditional non-medicinal part of Cornus officinalis, using modern column chromatographic techniques such as macroporous adsorbent resins colum, silica gel colum, chromatography gel colum and semi-preparative liquid chromatography techniques. Their structures were identified by modern wave spectroscopy techniques and electronic circular dichroism (ECD) and assigned as cornurtone A (1), cornucadinoside B (2), lacinilene C (3), 3, 12-dihydroxycadalene (4), cornucadinoside C (5). Compound 1 was new compound and compounds 2-5 were first isolated from leaves of Cornus officinalis. Compounds 2 and 3 had potential neuroprotective activities.

Three new compounds were isolated from the n-butanol fraction of Zingiber officinale (Ginger) peel by MCI Gel CHP-20, Sephadex LH-20, ODS and semipreparative high performance liquid chromatography. Their structures were identified as dendranthemoside C (1), zingpyranoside E (2), zingpyranoside F (3) by 1D-NMR, 2D-NMR, HR-ESI-MS, circular dichroism (CD) and ECD calculation techniques.

It aimed to research the chemical constituents of Solidago canadensis Lour. A new sucrose derivative was isolated from the the methanol extract of Solidago canadensis Lour. with the technologies of silica gel, microporous resin, Rp-18, and Sephadex LH-20 column chromatography. It was identified as 2, 4, 6, 1′, 3′, 6′-O-hexaisovaleryl sucrose by 1D NMR, 2D NMR, high-resolution mass spectrometry, and acid hydrolysis method. Its mass spectrometry fragmentation behaviors were analyzed using high-resolution mass spectrometry and found that compound 1 was easy to break the glycosidic bond to produce the fragment at m/z 415. The ion at m/z 415 continued to eliminate the isovaleryl group as neutral or non-neutral form to generate a series of daughter ions. Compound 1 could inhibit NO production on LPS-induced neuroinflammatory responses in BV2 microglial cells at the concentrations of 5, 10, and 20 μmol·L^-1 to exhibit neuroprotective effect. Its half maximal inhibition rate of NO was measured to be 13.96 ± 0.78 μmol·L^-1.

A new benzoic acid derivative, spinulacid (1), together with six known compounds ascomindone A (2), ascomindone C (3), monomethylsulochrin (4), barceloneic acid A (5), flufuran (6), and 5-hydroxymethyl-furaldehyde (7) were obtained from the rice fermentation extract of an endophytic fungus Penicillium spinulosum isolated from Emmenopterys henryi Oliv. by various chromatographic techniques. Their structures were elucidated by the analysis of NMR data, MS and comparison with literature. The biological activity results showed that compounds 1, 2, 5, and 6 exhibited significant proangiogenic activity in transgenic zebrafish at concentrations of 20 and 40 μmol·L^-1 (the animal experiment was approved by the Animal Ethical and Welfare Committee of Biology Institute, Shandong Academy of Science, the approval number is SWS20240611). Compounds 1 and 4 displayed moderate or strong antifungal activity against phytopathogen Fusarium graminearum with minimum inhibitory concentration (MIC) values of 12.5, and 6.25 μg·mL^-1, respectively. Besides, compound 4 was also found to show obvious antibacterial activity against Staphylococcus aureus and Erwinia carotovora with MIC values of 6.25 and 12.5 μg·mL^-1, respectively.

Through several chromatographic methods, such as silica gel, Sephadex LH-20 and high performance liquid chromatography (HPLC), six iridoids were isolated from the roots and rhizomes of Patrinia scabiosaefolia. By means of nuclear magnetic resonance (NMR) spectroscopy, ¹³C NMR calculation and mass spectrometry (MS), their structures were identified as patrinin A (1), patrinin B (2), loganin aglycone (3), isovillosol (4), 1, 3-dimethoxy-4, 7-dimethyl-octahyhro-cyclopenta[c]pyran-6, 7-diol (5) and viburnshosin A (6). Among them, compounds 1 and 2 were new compounds. Furthermore, the anti-influenza virus and anti-inflammatory activities of the isolates were evaluated.

Fourteen compounds including two new compounds were isolated from Kronopolites svenhedini (Verhoeff). These structures were identified as kronoponit A (1), kronoponit B (2), neoechinulin A (3), 2-(1, 1-dimethyl-2-propen-1-yl)-1H-indole-3-carboxaldehyde (4), uracil (5), p-hydroxy phenyl ethylamine (6), p-hydroxyphenylacetic acid (7), p-hydroxybenzoic acid (8), p-ethylbenzoic acid (9), 2-methyl-1, 4-benzenediol (10), 1, 2, 4-benzenetriol (11), gallic acid (12), gallic acid-3-methyl ether (13), and 4-methoxy-3, 5-hydroxybenzoic acid (14) by spectroscopic methods and literature. Among them, compounds 1 and 2 are new, while compounds 3-14 are reported here for the first time from K. svenhedini.

Synthetic cannabinoid N-(1-carbamoyl-2, 2-dimethylpropyl)-1-butylazole-3-formamide (ADB-BUTINACA), as a new psychoactive substance, shows strong stimulant and hallucinogenic effects. It can cause cardiovascular, renal and gastrointestinal diseases, and in severe cases, it can lead to death. However, there are few reports on toxicology studies of the ADB-BUTINACA metabolic pathway and its long-term effects on the organism and the molecular mechanisms behind it. In this study, the metabolic profile of rat serum after low, medium and high doses of ADB-BUTINACA (0.1, 1, and 5 mg·kg^-1) intervention were analyzed using UHPLC coupled with a Q-Orbitrap-MS (UHPLC-Q-Orbitrap-HRMS). The results showed that the intervention of ADB-BUTINACA could cause significant changes of 50 metabolites such as L-glutamate and 3-hydroxybutyrate, and nine metabolic pathways including alanine, aspartate and glutamate metabolism, retinol metabolism, and TCA cycle were disturbed. These findings provide a novel experimental and theoretical framework for further investigation of the toxicological mechanisms underlying ADB-BUTINACA-induced dysregulation of lipid and energy metabolism. Furthermore, they offer valuable insights that could facilitate the diagnosis and prevention of ADB-BUTINACA toxicity, thereby underscoring their significant implications for public health. The study was conducted in adherence to both the Declaration of Helsinki and the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals, and received approval from the animal experimental center at the Zhejiang Chinese Medical University (Ethical number: 20220718-11).

Jinqi Jiangtang Capsule (JQJTC) is one of the commonly used dosage forms of Jinqi Jiangtang formula, derived from the classic Qianjin Huanglian Pill, which is widely used in the treatment of diabetes mellitus. However, its pharmacokinetics is not still unclear. In this study, a stable and reliable method for the quantitative analysis of multiple components from JQJTC in mouse plasma and liver was established by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Then, the concentration changes of 16 components from JQJTC in plasma and liver of type 2 diabetic mice were determined and the kinetics was analyzed. The results demonstrated that the established UPLC-MS/MS method met the requirements for the determination of biological samples. The alkaloids, organic acids, flavonoids, and saponins were absorbed into mouse blood after JQJTC was administered by gavage, and there were significant differences in the rates of absorption, transport into liver and elimination and exposure levels of 16 components in plasma and liver. And the exposure of alkaloids, calycosin-7-glucoside and its glycosides, formononetin, and cycloastragenol in the liver were significantly higher than that in the plasma. The results provided a basis for further research on the pharmacodynamic substances of JQJTC. The use of all experimental animals has been approved by the Ethics Committee of Laboratory Animal of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM2401310001).

In order to further distinguish the differences of compounds in different medicinal parts of Angelica (head, body and tail), our study used UHPLC-QE-MS combined with non-targeted metabolomics technology to identify the different compounds in different medicinal parts of Angelica. Principal component analysis (PCA) and OPLS-DA were used to screen the differential metabolites, and the related pathways were compared and analyzed. Eighteen types of 1 072 metabolites were identified from different medicinal parts of Angelica sinensis, mainly terpenoids, phenylpropanes, lipids and their derivatives, alkaloids, flavonoids, organic acids and their derivatives, etc. The comparison between Angelica head and Angelica body, Angelica head and Angelica tail, Angelica body and Angelica tail showed 530, 565, 474 different metabolites, among which kaempferol, cinnamic acid, chlorogenic acid, ferulic acid, ligustilide, liquiritigenin, and rutin were mainly enriched in Angelica tail, naringin, apigenin were mainly enriched in Angelica body, estradiol, ligustrazine were mainly enriched in Angelica head; differential metabolites are concentrated in flavonoid biosynthesis, phenylalanine metabolism, indole alkaloid biosynthesis, tryptophan metabolism, flavonoid and flavonol biosynthesis and other pathways. In this study, UHPLC-QE-MS non-targeted metabolomics technology can effectively analyze the differential metabolites of different medicinal parts of Angelica sinensis, providing scientific support for clinical rational and accurate application of different medicinal parts of Angelica sinensis.

Cocktail probe drug method was used to evaluate the effect of cold treatment drugs such as Gegen Decoction on cytochrome P450 (CYP450) enzyme activity in rat liver. The in vitro incubation system of rat liver microsomes was optimized. Based on LC tandem mass spectrometry (LC-MS/MS), an analytical method for simultaneous determination of the content of metabolites of each subenzyme probe in rat liver microsome CYP450 enzyme was established. Cocktail probe drug method was used to characterize the effects of Gegen Decoction, a classical prescription for the treatment of wind-cold cold, and acetaminophen, chlorpheniramine maleate, anhydrous caffeine and nacotine hydrochloride, which were commonly used in the treatment of cold, on the activity of CYP2D6, CYP2C9, CYP3A4 and other sub-enzymes in rat liver microsomes, so as to provide reference for the safety of clinical drug combination. The results showed that the established analysis method was stable and reliable, which met the requirements of biological sample determination. After optimization, the protein concentration of rat liver microsomes in the incubation system was 3.00 mg·mL^-1, the incubation time was 240 min, and the terminator was acetonitrile. The K_m values of three CYP subenzyme specific probe substrates dextromethorphan, testosterone and tolbutamide were 21.49, 87.33 and 354.7 μmol·L^-1, respectively. The effectiveness of the established incubation system was verified by positive inhibitors. Compared with the blank control group, when the concentration of each Western medicine and the concentration of Gegen Decoction extract were within 100.00 μmol·L^-1 and 3.00 mg·mL^-1, respectively, Gegen Decoction extract, chlorpheniramine maleate and noscapine hydrochloride had inhibitory effects on CYP2C9 and CYP2D6 enzymes in rat liver microsomes; anhydrous caffeine had inhibitory effects on CYP2C9 and CYP3A4 enzymes in rat liver microsomes; no significant inhibitory effect on acetaminophen; the induction effect of narcotine hydrochloride on CYP3A4 enzyme in rat liver microsomes was greater than 40% of the activity of positive inducer, suggesting that there may be a certain risk of drug interaction when combined with narcotine hydrochloride, and attention should be paid to the dose of drug treatment. The experimental protocol strictly adhered to the guidelines of the Ethics Committee of Animal Research of Guangdong Pharmaceutical University (Approval: gdpulacspf2022137).

The study aims to establish HPLC fingerprint and multi-index content determination method of Guanxin Qiwei tablets and provide scientific basis for its quality control. The fingerprints of 18 batches of Guanxin Qiwei tablets were established by Shim-pack GGIST HP C₁₈ chromatographic column, and analyzed comprehensively in combination with the Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition). Cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used for stoichiometric study. HPLC-MS/MS method was established for simultaneous determination of 9 components. A total of 22 common peaks were identified in 18 batches of Guanxin Qiwei tablets fingerprint, and the similarity was 0.952-0.998, 9 common peaks were identified. They were No. 1 gallic acid, No. 3 protocatechuic acid, No. 8 ellagic acid, No. 9 salvianolic acid B, No. 12 luteolin, No. 13 apigenin, No. 19 dehydrodiisoeugenol, No. 20 cryptotanshinone and No. 21 tanshinone ⅡA. CA and PCA analysis grouped 18 batches of Guanxin Qiwei tablets into 3 categories: S1-S4 (manufacturer A) was grouped into one category, S5-S8 (manufacturer B) was grouped into one category, and S9-S18 (manufacturer C and D) was grouped into one category. Under OPLS-DA analysis mode, 14 quality differentiators were selected with the variable important projection (VIP) greater than 1 as the standard, and all of them had significant differences. The linear relationship of the 9 components was good in their respective ranges, and the linear correlation coefficient r was greater than or equal to 0.099 9. Precision RSDS were all lower than 3.00%. The stability and repeatability were good, RSD lower than 5.00%; The average recoveries were 96.58%-106.28%, RSD was 2.68%-6.45%. This method is efficient and stable, and can be used for quality control of Guanxin Qiwei tablets.

This study investigated the material basis of Huoluoxiaolingdan in treating diabetic peripheral neuropathy (DPN) through ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and network pharmacology. UPLC-Q-TOF-MS/MS combined with PeakView^TM 1.2 software and Molecule Profiler^TM software were used to analyze the the chemical components of Huoluoxiaolingdan and blood-absorbed ingredients in normal rats and rats with DPN induced by high fat diet combined with low dose streptozotocin injection. Swiss Target Prediction database, GeneCards and other databases were used to search the corresponding targets of active ingredients and disease targets. The intersection targets were obtained using Venny 2.1 platform, which were then imported into the STRING platform and Cytoscape 3.10.1 software to construct the protein-protein interaction network and the "component-target" network relationship diagram, and the core components and core targets were analyzed. GO and KEGG pathway enrichment analysis of key targets were performed. All experiments were approved by the experimental Animal Ethics Committee from Nanjing University of Chinese Medicine (No. 202310A023). A total of 83 chemical components were identified, including 52 terpenoids such as tanshinone Ⅱ_A, 11 phthalides such as Z-ligustilide, 15 organic acids such as ferulic acid, 4 coumarins and 1 phenol. Additionally, 15 prototype components and 29 metabolites were identified in normal rats' plasma, and 17 prototype components and 32 metabolites were identified in DPN rats' plasma. Network pharmacology results show that 5 core components such as 3-acetyl-11-keto-β-boswellic acid and 11-keto-β-boswellic acid may act through 27 core targets such as TNF and IL6 to regulate AGE-RAGE and PI3K/Akt and other signaling pathways so as to play a therapeutic role in treatment of DPN. The study efficiently analyzed the constituents in vitro and blood-absorbed ingredients of Huoluoxiaolingdan and the cracking regularity of the main compounds, and the core components of its treatment of DPN were analyzed in combination with network pharmacology, which can provide reference for further research of the pharmacodynamic substantial basis and mechanism of Huoluoxiaolingdan in the treatment of DPN.

The study of micromechanical behavior during tablet pressing is often limited to phenomenological studies, accurate calibration of the discrete element model parameters of binary particles is a prerequisite for conducting modeling research on tablet compression. In this study, we take pregelatinized starch and microcrystalline cellulose as the research objects, and apply the Edinburgh elasto-plastic adhesion (EEPA) contact model to establish a discrete elemental simulation model for binary material pressing. Taking tablet force-hardness and force-volume reduction as response values, the optimal values of the discrete meta-parameters that significantly affect tablet pressing are obtained by applying Plackett-Burman design, Latin hypercubic sampling, Kriging model, and Non-dominated Sorting Genetic Algorithm (NSGA-Ⅱ) calibration. The results obtained the optimum combination of discrete element method (DEM) parameters for pregelatinized starch, Poisson's ratio 0.257, shear modulus 1×10⁹ Pa, granule-particle static friction coefficient 0.165, unit normal stiffness 2.419 2×10⁹ N·m^-3, unit tangential stiffness 7.954 6×10⁹ N·m^-3, and strength of adhesive force -0.009 155 8 N. For microcrystalline cellulose, Poisson's ratio 0.381, shear modulus 1.04×10⁹ Pa, particle-particle static friction coefficient 0.719, unit normal stiffness 3.171 5×10⁹ N·m^-3, unit tangential stiffness 6.746 2×10⁹ N·m^-3, and strength of adhesion -0.038 7 N. For optimum combinations of the DEM parameters for the binary blend of excipients, particle-particle collision recovery coefficient 0.1, unit normal stiffness 9.947 1×10⁹ N·m^-3, unit tangential stiffness 1.994 5×10⁹ N·m^-3, and adhesion force strength -0.060 35. The simulation results under the optimal parameter combination are similar to the experimental results, indicating that the calibrated parameters can be used for discrete element simulation research and provide theoretical basis and data support for the subsequent intelligent and continuous production of tablets.

In this study, licorice-derived vesicle-like particles (LVLPs) were used as carriers, and licochalcone-A (LCA), a signature active ingredient of the same source, was used as a model drug to construct a drug-loaded LVLP@LCA nanodelivery system, and to characterize and evaluate its in vitro properties and anti-inflammatory activity. Licochalcone-A (LCA), a signature active ingredient of traditional Chinese medicine from the same source, was used as a model drug to construct a drug-loaded exocyst-like nano-delivery system, LVLP@LCA, and its in vitro properties and anti-inflammatory activities were characterized and evaluated. The LVLP@LCA nanodelivery system was prepared by extracting the exocyst-like nanoparticles by gradient centrifugation and loading the anti-inflammatory drug LCA by ultrasonication. The LVLP@LCA nanoparticles were prepared with a particle size of about 160 nm and a tea saucershaped bilayer structure, with a high encapsulation rate and drug loading capacity. The in vitro results showed that LVLP@LCA further enhanced the ability of LCA to inhibit the proliferation of inflammatory cells and reduce the levels of ROS and NO in inflammatory cells. Meanwhile, ELISA and qRT-PCR results showed that LVLP@LCA significantly reduced the secretion and mRNA expression of IL-6, IL-1β, TNF-α, CCL5, CCL17 and other related inflammatory factors and chemokines. It was demonstrated by Western blot that LVLP@LCA reduced the expression of inflammation-inducing factor interleukin 6 (IL-6) through the JAK/STAT pathway, and then inhibited the activation of inflammatory response. The present study provides a theoretical basis for the comprehensive anti-inflammatory effect of LVLP@LCA and a new way of thinking for the application of Glycyrrhiza glabra as a traditional Chinese medicine against atopic dermatitis.

JAZ proteins, as inhibitors in the jasmonic acid (JA) signaling pathway, play a crucial role in regulating plant growth and development, as well as the biosynthesis of secondary metabolites in plants. To explore the functions of the JAZ gene family in Tripterygium wilfordii, our study systematically identified the members of the JAZ gene family in T. wilfordii. We analyzed their physicochemical properties, chromosome localization, phylogenetic tree, and protein conserved motifs. Additionally, we investigated the expression patterns of TwJAZs in different tissues, constructed a gene regulatory network map, and ultimately cloned the full-length sequences of 18 JAZ genes. The results showed that the 18 TwJAZs were unevenly distributed across 12 chromosomes, encoding amino acid numbers ranging from 122 to 525, with molecular weights of 13.87 to 54.73 kDa, and isoelectric points ranging from 6.83 to 10.27. Subcellular localization prediction indicated that 13 TwJAZs were localized in the nucleus, while 5 TwJAZs were located in the cytoplasm and chloroplasts. The phylogenetic tree analysis revealed that the JAZ family proteins of T. wilfordii could be divided into five subfamilies, with members of the same subfamily sharing similar conserved motifs. Expression pattern analysis demonstrated that TwJAZs were predominantly expressed in flowers, leaves, and peeled stems, with most TwJAZs showing the highest expression levels after 4 hours of methyl jasmonate (MeJA) induction. The transcription factor regulatory network shows that TwJAZs are strongly correlated with transcription factor families such as AP2/ERF-ERF, NAC, and bHLH. This study comprehensively identified all the JAZ gene family sequences in T. wilfordii, initially clarifying the structural and functional characteristics of the TwJAZs, and laying an important foundation for further research on the functions and regulatory mechanisms of TwJAZs.

Based on the genome and transcriptome data of Salvia miltiorrhiza, a cytochrome P450 gene annotated as SmCYP72A395, which was highly expressed in the periderm of S. miltiorrhiza root was cloned. The total length of the cDNA sequence of SmCYP72A395 was 1 578 base pairs, encoding 525 amino acids. The predicted molecular weight of the protein was 59.9 kDa. The physicochemical properties, subcellular localization, protein structure, and conserved domains were predicted by online bioinformatic tools. The theoretical isoelectric point of SmCYP72A395 was 8.68, with a transmembrane domain in the protein. This gene was highly expressed in the flower, leaf, and root periderm tissues of S. miltiorrhiza. To further identify the biological function of SmCYP72A395, the transgenic hairy roots with SmCYP72A395 overexpressed (SmCYP72A395-OE) and RNA interference (SmCYP72A395-RNAi) were constructed, and the content of tanshinone compounds was detected by UPLC between these transgenic lines and control line (haboring the vector plasmid in the transgenic line). Compared with the control line of transgenic hairy roots, the content of dihydrotanshinone Ⅰ, cryptotanshinone, tanshinone Ⅰ and tanshinone ⅡA in the SmCYP72A395-OE lines was significantly less than those in the control line. On the contrary, the content of dihydrotanshinone Ⅰ, cryptotanshinone, and tanshinone Ⅰ was higher in the SmCYP72A395-RNAi lines than those in the control line. These results demonstrated that SmCYP72A395 played a negative role in the regulation of tanshinone accumulation in S. miltiorrhiza. This study lays the foundation for further elucidating the biosynthesis and regulatory pathways of tanshinone compounds in S. miltiorrhiza.