As a novel iron-dependent form of cell death, ferroptosis is characterized by the excessive accumulation of phospholipids containing polyunsaturated fatty acids (PUFA) on the cell membrane and peroxidation. Lipid droplets are always in the dynamic transition of generation and decomposition, play a central role in regulating lipid metabolism, and are always in the dynamic transition of generation and decomposition. Lipid droplet metabolism is closely related to the occurrence of ferroptosis and plays an important role in the disease caused by ferroptosis. This review firstly focuses on the lipid droplet metabolism process and its effects on the storage and release of PUFA, and further elucidates the regulatory mechanism and key regulatory proteins of lipid drop metabolism on ferroptosis, in order to reveal the intrinsic relationship between lipid droplets and ferroptosis, and provide a new strategy for disease prevention and treatment.

Brother of regulator of imprinted sites (BORIS), also known as CCCTC binding factor-like (CTCFL), is a relatively newly discovered cancer-testis antigen. Drug development related to BORIS has been carried out in multiple directions, including small molecules, small RNA molecules, polypeptides, vaccines, and cellular therapies. Due to its unique ability to interfere with the higher-order spatial structure of the genome, BORIS may represent a new class of drug targets. Here we systematically review the molecular biology research results related to BORIS, including the diversity of its gene products, the multipartite interactions mediated by BORIS, the subsequent impact on signaling pathways, and current drug development strategies, in order to gain a better understanding of the molecular mechanisms of BORIS in both upstream and downstream regulation networks and to identify potential research directions for further breakthroughs.

Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.

At present, brain disease has become a "killer" in the field of general health, and the existence of blood-brain barrier has become one of the challenges in drug delivery into the brain. According to studies, cell membrane coating technique can endow nanoparticles with the characteristics of immune escape, long circulation, targeted delivery, and so on. Therefore, membrane biomimetic nanoparticles have been widely used in the field of disease treatment. Among them, the cell membrane derived from immune cells, tumor cells, and stem cells can cross the blood-brain barrier through the transcellular pathway and cell bypass pathway, which is used to prepare biomimetic membrane nanoparticles to break through the blood-brain barrier to achieve the treatment of brain diseases. What's more, the brain targeted ability of biomimetic nanoparticles would be further enhanced by modifying the cell membrane with peptides. This paper introduces the preparation methods of membrane biomimetic nanoparticles, expounds in detail the way that cell membrane coated nanoparticles break through the blood-brain barrier and achieve efficient intracerebral drug delivery. It also summarizes the prospects and challenges of this novel drug delivery system in the treatment of brain diseases, providing a reference for the research of membrane biomimetic nanoparticles in the treatment of brain diseases.

After entering the body from the drug delivery site, antitumor nanomedicines need to cross a series of physiopathological barriers to reach the target site of action to effectively exert antitumor therapeutic effects. The ligand modification strategy is a classic method to enhance the efficiency of nanomedicine delivery in vivo, but the contradiction between the single ligand modification strategy, which is characterized by unity and stage, and the in vivo delivery process, which is characterized by versatility and whole-process characteristics, determines that nanomedicines modified by a single ligand alone cannot satisfy the target efficacy requirements. Therefore, the use of multiligand combinatorial modification strategies by virtue of nanomedicine surface area advantages is key to advancing the next generation of smart nanomedicines. In this paper, on the basis of summarizing and classifying the commonly used functional ligands for in vivo delivery, the advantages and research progress of multiligand combination modification of antitumor nanomedicines are discussed with special focus, and the multiligand combination modification is classified as synergistic and complementary according to the combination of the ligands, which is of great significance to ensure that antitumor nanomedicines can overcome the multiple physiopathological barriers to achieve precise delivery.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Biomacromolecule drugs have been increasingly used in clinical practice due to their distinct advantages, including precise targeting, small dose, high safety and activity. However, owing to their high molecular weight, strong hydrophilicity, and poor stability in the gastrointestinal tract, the oral bioavailability of the biomacromolecule drugs remains extremely poor. As a novel and innovative technology for active drug delivery, gastrointestinal microneedles hold immense potential in the oral delivery of biomacromolecule drugs because of their low-invasive nature and high permeation enhancement effects. This review primarily summarizes the actuating force, design strategies, fabrication techniques, and applications of gastrointestinal microneedles for the oral delivery of biomacromolecule drugs. Additionally, the challenges and further perspectives in the development this technology are presented, aiming to promote the subsequent research and clinical translation of gastrointestinal microneedles, and to provide a new efficient and safe strategy for oral delivery of biomacromolecule drugs.

Misuse of pyrrolizidine alkaloid (PA)-containing herbs is the major cause of hepatic sinusoidal obstruction syndrome (HSOS) in China. And diuretics are among the most commonly used medications for the treatment of PA-induced HSOS in clinical practice. As a traditional diuretic in traditional Chinese medicine, the diuretic mechanism of Alismatis Rhizoma (AR) has not been fully clarified, and there is no report on AR ameliorating PA-induced HSOS from a diuretic point of view. Therefore, this study aims to investigate the therapeutic potential of alisol B 23-acetate (AB23A) against acute liver injury induced by senecionine (a representative toxic PA) in mice, and to further elucidate its effect on impaired water-liquid balance in mice exposed to PA. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (Registration number: PZSHUTCM220808017). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Model of mice was induced by a single oral exposure of senecioine (50 mg·kg^-1) (SEN group), and AB23A (40 mg·kg^-1) intervention group (AB23A+SEN group), solvent control group (Ctrl group) and AB23A control group (AB23A group) were set up. The results showed that AB23A could significantly attenuate the levels of serum biochemical indices of liver functions in senecioine-induced acute liver injury mice, as evident by alleviated hepatocyte necrosis and hepatic sinusoidal stasis. AB23A also improved kidney function of mice exposed to senecionine, fascinated urinary excretion and repaired electrolyte disorders, as well as decreased content of senecioine metabolites. Further, the protein and mRNA expression of genes related to the water balance pathway were measured. AB23A could significantly down-regulate the elevated protein and mRNA expression levels of aquaporin 2 (AQP2) and angiotensin Ⅱ type 1 receptor, and inhibit the transport of AQP2 to the apical plasma membrane induced by senecionine exposure. AB23A also significantly decreased serum levels of angiotensin Ⅱ. In vitro studies further confirmed that AB23A regulates AQP2 expression in renal inner medullary collecting duct cells 3 (IMCD3). These data indicate that AB23A regulates the expression of AQP2 in renal medulla, thereby affecting its water reabsorption in mice with senecionine-induced acute liver injury. This work achieves a better understanding of the diuretic effect of AR, and provides experimental foundation and theoretical basis for the treatment of PA-induced acute liver injury by AR in clinics.

Nicotinic acetylcholine receptors (nAChRs) belong to ligand-gated ion channel receptors, of which α7 nAChR subtype is widely distributed in the cerebral cortex, thalamus, hippocampus, and also identified in microglia, macrophages, bone marrow cells, etc. Previous studies revealed that α7 nAChR is closely related to the function of the cholinergic anti-inflammatory pathway, and is a vital target for drug development of Alzheimer's disease and schizophrenia. The establishment of a stable α7 nAChR in vitro drug screening system is crucial for the efficient screening of novel drugs targeting this target. Recombinant expression of different subtypes of nAChRs on Xenopus laevis oocyte membranes and current detected by two-electrode voltage clamp (TEVC) is an advanced and complex model for novel drug screening. Molecular chaperones can assist the assembly of some nAChR subunits to form functional receptors, providing a stable expression model for the screening of compounds targeting this receptor. In this study, a molecular chaperone gene of α7 nAChR, transmembrane protein 35A (Tmem35a), was isolated and cloned from rats. We constructed the recombinant expression vector and obtained the cRNA of Tmem35a by in vitro transcription technique. Two cRNAs (Tmem35a and α7) were mixed and injected into X. laevis oocytes for expression. Then, the effects of this molecular chaperone on the current expression and pharmacological properties of α7 nAChR were evaluated by the TEVC. The results revealed that TMEM35A, also known as novel acetylcholine receptor chaperone (NACHO) could effectively increase the expression of α7 nAChR protein on oocyte membranes, and the amount of α7 nAChR protein was increased about 1-fold. The peak current induced by agonist acetylcholine (ACh) was increased about 10-fold. After injection of Tmem35a cRNA, the median effect concentration (EC₅₀) value of α7 nAChR to agonist ACh is 228.5 μmol·L^-1, which shows almost no difference from native α7 nAChR (EC₅₀: 223.3 μmol·L^-1), indicating the preservation of the normal properties of α7 nAChR. The results of this investigation indicate that the molecular chaperone NACHO effectively assists the heterologous expression of α7 nAChR in X. laevis oocytes, which provides a model for screening the potency of lead compounds targeting α7 nAChR. All animal experiments in this study were reviewed and approved by the Ethics Committee of Guangxi University (approval number: GXU-2023-0249).

N-type voltage-gated calcium (Ca²⁺) channels (N-type VGCC, Ca_V2.2) mediate Ca²⁺ influx in response to action potential at the presynaptic terminal, and play an important role in synaptogenesis, neurotransmitter release and nociceptive signal transduction. It is a new target for the development of drugs for the treatment of neuralgia (chronic pain) and other major diseases. Due to the difficulty of calcium channel expression in vitro and the detection of channel current, there is a great lack of new drug screening models. In this study, we established and optimized the electrophysiological drug screening model using Xenopus laevis oocytes for the recombinant expression of Ca_V2.2 in vitro (this study were reviewed and approved by the Ethics Committee of Guangxi University, approval number: GXU-2023-0249). Firstly, the linear plasmids encoding cDNA of major subunit α1B and auxiliary subunits α2δ1 and β3 of rat Ca_V2.2 were used as templates for in vitro transcription to generate their related mRNA (cRNA), after which three kinds of cRNA were injected into Xenopus laevis oocytes at the mass ratio of 2∶1∶1 for expression. The two-electrode voltage clamp (TEVC) technique was used to detect the inward current produced by Ca_V2.2. At the same time, the expression conditions of Ca_V2.2 were optimized, and its gating function was characterized from the aspects of channel activation and inactivation. The results showed that 3-5 days after cRNA microinjection, stable Ca_V2.2-mediated barium ion (Ba²⁺) currents were successfully detected. The interference of endogenous potassium channels and Ca²⁺-activated chloride channels can be eliminated by tetraethylammonium hydroxide (TEAOH) and 1, 2-bis(2-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid tetrakis (BAPTA-AM) treatment. The maximum potential for Ca_V2.2 activation is 0 mV, and the current reverses to be outward when the membrane potential is greater than +50 mV. By fitting the steady-state activation and inactivation curves, the half-maximal activation potential and half-maximal inactivation potential of Ca_V2.2 are identified as -15.9 and -60.2 mV. In this study, a stable Ca_V2.2 expression system was established based on Xenopus laevis oocytes. The in vitro expression system can provide a new way for the screening of Ca_V2.2 active compounds or lead drugs.

In this study, we investigated the anti-inflammatory effect and mechanism of tilianin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The cell viability was detected by cell counting kit-8 (CCK-8) assay. The content of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immuno sorbent assay (ELISA) kits. The content of nitric oxide (NO) was assayed by Griess reagent method. The level of intracellular reactive oxygen species (ROS) was detected by 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The protein levels of Toll like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88), nuclear factors κB p65 (NF-κB p65), phosphorylated nuclear factor κB p65 (p-NF-κB p65), nuclear factor κB inhibitory protein α (ⅠκBα) and phosphorylation nuclear factor κB inhibitory protein α (p-ⅠκBα) were detected by Western blot. The mRNA and protein levels of NLRP3, pro-IL-1β, pro-IL-18 and pro-caspase-1 were detected by qRT-PCR and Western blot. Immunofluorescence staining was used to detect the nuclear translocation of NF-κB p65. The effect of tilianin on the TLR4/Myd88/NF-κB signaling pathway was further validated by using the TLR4 signaling inhibitor restatorvid (TAK242). The results showed that tilianin significantly reduced the levels of TNF-α, IL-6 and NO in the supernatant of RAW264.7 cells and decreased the content of intracellular ROS. Tilianin reduced the levels of TLR4, Myd88, p-NF-κB p65 and p-ⅠκBα protein and nuclear translocation of NF-κB p65. Tilianin could reduce the protein levels of NLRP3, pro-IL-1β, pro-IL-18 and pro-caspase-1. Tilianin significantly inhibited the mRNA levels of NLRP3 and pro-IL-1β. The above research results indicated that tilianin could significantly alleviate the LPS-induced inflammatory response in RAW264.7 cells and its mechanism might be related to downregulate the TLR4/Myd88/NF-κB signaling pathway to inhibit NLRP3 inflammasome.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer known for the poor prognosis due to its strong invasiveness, high recurrence rate, and lack of effective treatment. Therefore, there is an urgent need to find targeted therapy for TNBC. Cathepsin A (CTSA) is an acidic serine carboxypeptidase that is highly expressed in various tumor tissues. However, the role and molecular mechanism of CTSA in TNBC are still unclear. This study found that the expression of CTSA was upregulated, and the high expression of CTSA was positively correlated with the poor prognosis of TNBC. The results further showed that knocking down CTSA inhibited the proliferation, invasion, and colony formation of TNBC cells, improved drug sensitivity of cells, and inhibited the progression of TNBC. Mechanistically, CTSA inhibited the ubiquitination and degradation of the promyelocytic leukemia protein (PML) protein by blocking the interaction between PML and its E3 ubiquitin ligase RNF4, thus maintaining the stability of PML nuclear bodies (PML-NBs). The inhibitor of CTSA had a positive therapeutic effect on inhibiting the characteristics of TNBC stem cells. In conclusion, this study demonstrates that inhibiting CTSA to decrease the stability of PML protein may be a promising therapeutic strategy for TNBC. All animal experiments in this experiment were approved by the Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College (approval number: IMB-20240326D502).

The purpose of this study was to investigate the intervention effect and mechanism of Lycium barbarum leaves on letrozole-induced polycystic ovary syndrome (PCOS) mice. The PCOS model was prepared by letrozole combined with high-fat diet. After successful modeling, 40 mice were randomly divided into PCOS group, positive drug metformin group, low-dose Lycium barbarum leaves group, and high-dose Lycium barbarum leaves group. The corresponding drugs were given by gavage for 29 days. At the end of the experiment, the eyeballs were removed for blood collection and ovarian tissue was collected. The ovarian mass, fasting blood glucose (FBG), fasting insulin (FINS), testosterone (T), anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E₂) levels were measured in each group. The morphology of ovarian tissue was observed by hematoxylin-eosin staining, and the oocytes, cystic follicles and corpus luteum were counted. Cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. The animal experiment process was approved by the Animal Ethics Committee of Nanjing University of Traditional Chinese Medicine. The results showed that the estrous cycle of PCOS mice was disordered. Compared with the PCOS group, the Lycium barbarum leaves group can significantly reduce the ovarian damage of mice, reduce the number of cystic dilated follicles, and normalize the estrous cycle. After the intervention of Lycium barbarum leaves, the levels of FBG, FINS, T, AMH, LH, FSH and LH/FSH were significantly decreased (P < 0.05), while the level of E₂ was significantly increased (P < 0.001). In addition, Lycium barbarum leaves can regulate the disorder of intestinal flora diversity in PCOS mice, increase the abundance of Bacteroidetes, and reduce the abundance of Firmicutes, Ileibacterium, Romboutsia and Faecalibaculum. In summary, Lycium barbarum leaves can play a therapeutic role in PCOS mice by improving insulin resistance, regulating reproductive hormone disorders and gut microbiota imbalance. It provides scientific basis and useful reference for the rational utilization and development of Lycium barbarum leaves.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Studies on chemical constituents in the rhizome of Dalbergia rimosa Roxb. The chemical constituents from the ethyl acetate part of D. rimosa were isolated and purified by silica gel, MCI gel, Sephadex LH-20 gel and semi-preparative HPLC, and the stuctures were identified by spectral method. Thirteen compounds were isolated from the ethyl acetate part of the rhizome of D. rimosa and identified as dalbergiaisoflavones A, B (1, 2), formononetin (3), 7,4′-dimethoxyisoflavone (4), 4′,6,7-trimethoxyisoflavone (5), biochanin A (6), prunetin (7), 7-O-methyltectorigenin (8), 3′-hydroxydaidzein (9), orobol 7,3′-dimethyl ether (10), 2′,7-dihydroxy-4′,5′- dimethoxyisoflavone (11), pruinosanone E (12), caviunin (13). Compounds 1 and 2 are new compounds, and compounds 3-13 were isolated from this plant for the first time. Compounds 9 and 11 had remarkable scavenging effect on DPPH free radicals.

Four furan α-butenolactones were isolated from 50% acetone extract of tuber of Alisma orientale by silica gel column, chromatography gel column and high performance liquid chromatography techniques. Their structures were identified by modern wave spectroscopy techniques and electronic circular dichroism (ECD) and assigned as (5R)-5-hydroxy-3, 4-dimethylfuran-2(5H)-one (1), 5-hydroxy-3, 5-dimethylfuran-2(5H)-one (2), 5-hydroxy-4-(1-methylethyl)-2(5H)-furanone (3) and alismanoid A (4). Compound 1 was new compound and compounds 2–4 were first isolated from Alisma orientale. Compound 1-4 had potential antifibrotic activities.

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S, 8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Eleven compounds were isolated and purified from the ethyl acetate part of 80% ethanol extract of Ferula feruloides root by a combination of normal-phase silica gel column chromatography, Sephadex LH-20 dextran gel column chromatography and semi-preparative liquid chromatography and then modern wave spectrometry methods (NMR, MS, UV, IR) were used to identify the structures of the compounds, which were identified as baigene D (1), baigene E (2), baigene F (3), β-kirialovin (4), α-kirialovin (5), falcarindiol (6), ammoresinol (7), dshamirone (8), 2, 3-dihydro-7-hydroxy-2S^*, 3R^*-dimethyl-3-[4-methyl-5-(4-methy1-2-furyl)-3(E)-pentenyl]-furo[3, 2-c]coumarin (9), 2, 3-dihydro-7-hydroxy-2S^*, 3R^*-dimethyl-2-[4, 8-dimethyl-3(E), 7-nonadi-enyl]-furo[3, 2-c]coumarin (10), and baigene C (11). Compounds 1-3 are new coumarin analogues, and compounds 4-6 are firstly isolated from F. feruloides. The anti-proliferative activity of compounds 5, 7-11 against human gastric cancer (MKN-45) cells was evaluated using MTT assay, which showed that compounds 7-11 exhibited strong inhibitory activity, and compound 5 exhibited weak inhibitory activity.

From an aqueous extract of the Angelica sinensis root head (guitou), nine pairs of lignanoid enantiomers [(+)-/(-)-1-(+)-/(-)-9], including three pairs of new structures [(+)-/(-)-1-(+)-/(-)-3] and two pairs of chiral separated enantiomers for the first time [(+)-/(-)-4 and (+)-/(-)-5], were isolated and chirally separated by column chromatography over different types of resin, normal and reversed phase silica gels, together with HPLC techniques using reversed phase and chiral columns. Their structures were determined by spectroscopic data analysis, theoretic calculation of electronic circular dichroism (ECD) spectra, and single-crystal X-ray diffraction. The chiral separated new enantiomers named (+)-/(-)-angelignanins Q-T [(+)-/(-)-1-(+)-/(-)-4] and (+)-/(-)-daphneresinol [(+)-/(-)-5], respectively.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Astragalus polysaccharides are the most immunoregulatory active and abundant substances in Astragalus, with anti-tumor, anti-viral, and immune-promoting biological activities. They have been widely used in clinical practice. Previous studies have found that Astragalus polysaccharides are mainly composed of two different polysaccharides, APS-Ⅰ (> 2 000 kDa) and APS-Ⅱ (10 kDa), with APS-Ⅱ (10 kDa) being the most active component of Astragalus polysaccharides. We used α-1, 4-glucan endo-hydrolysis enzyme to degrade APS-Ⅱ into oligosaccharides, and screened the immune activity of oligosaccharides in vitro. We found that the overall immune activity of 2-9 oligosaccharides was low, while the immune activity of 10-14 oligosaccharides was strong, and the activity was better than that of untreated APS-Ⅱ. To investigate the key structural features of APS-Ⅱ oligosaccharides that play a role in immune activity, we used MALDI-TOF-MS biochemical mass spectrometry and high-resolution mass spectrometry instrument ESI-Q Exactive-MS to analyze the APS enzymatic oligosaccharides. By comparing, we found that 10-14 oligosaccharides contain 1→4 and 1→6 branched structures with coexisting linkages, suggesting that 1→4 and 1→6 linkages in branched structures are key structural features that play a role in the immune activity of APS-Ⅱ, laying a theoretical foundation for the structure-activity relationship of Astragalus polysaccharides and oligosaccharides.

Phellodendri Chinensis Cortex (PCC) featured with thick cortex and bright-yellow is considered to be of high quality according to traditional appearance traits evaluation mode. However, the correlation between appearance traits and internal quality of PCC has not been scientifically revealed. Here, based on the theory of "Quality Evaluation Through Morphological Identification", the correlation of both sides was studied systematically. Firstly, the thickness of PCC slices was measured by vernier calipers for classification, and the colour of PCC slice was estimated by naked eyes and automatic colorimeter and classified. Secondly, high performance liquid chromatography (HPLC) was used to establish fingerprint chromatogram containing 12 characteristic peaks, and the contents of moisture and ethanolic extractive were determined as well. The correlation among the appearance traits of PCC slice (including the thickness and the spatial values of colour of PCC slice powder: L^*Lightness, a^*Red-Green, b^*Yellow-Blue) and peak areas of 12 characteristic peaks, contents of moisture and extractive were explored through multivariate statistical analysis tools, including Pearson's correlation analysis, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (PLS-DA) and analysis of variance (ANOVA). Association analysis results showed the morphological parameters (thickness and color) are significantly correlated with 2 kinds of principle chemical constituents (alkaloids and phenolic acids), among them, 5 major constituents including 2 isoquinoline alkaloids and 3 feruloylquinic acids were simultaneously quantitatively analyzed under the same chromatographic condition for establishing a correspondence between appearance traits and content of internal substances, and the sum of the contents of the five components was significantly higher in the thickness ≥ 4 mm (13.15% ± 2.25%) and bright yellow samples (12.14% ± 2.00%) than that in the thickness < 4 mm (10.89% ± 1.41%) and dark yellow samples (10.32% ± 2.41%). The research results confirm that thickness and colour, two main appearance parameters of PCC slice, can be used as the indicators for evaluating the quality PCC slice, which to some extent interprets the scientific connotation of traditional evaluation theory of "thick and yellow are better". At the same time, the results provided substantial data and foundation for the establishment of commodity grade standards of PCC slice.

In this study, the effective substance group and molecular mechanism of Rhei Radix et Rhizoma-Persicae Semen combination (RRR-PS) in activating blood circulation and dispelling blood stasis were investigated by integrating efficacy experiments, network pharmacology and HPLC. The rat model of blood stasis syndrome was established, and the blood rheology index and coagulation four comprehensive evaluation were carried out. The results showed that compared with the model group, the whole blood viscosity, erythrocyte sedimentation rate and erythrocyte aggregation index of the rats in the RRR-PS group were significantly callback (P < 0.01). Network pharmacology found that RRR-PS combination exerted the effect of activating blood circulation and dispelling blood stasis by acting on calmodulin-1 (CALM1), nitric oxide synthase-2 (NOS2), glucocorticoid receptor (NR3C1) and other targets, regulating platelet activation, peroxisome proliferator-activated receptor (PPAR), vascular endothelial growth factor A (VEGF) and other signaling pathways, and found key components: sennoside B, (+)-catechin, emodin, physcion, rhein, aloe-emodin, chrysophanol, gallic acid. HPLC was used to explore the dissolution rate of key components. The results showed that the contents of catechin, emodin, chrysophanol and physcion were significantly increased after RRR-PS combination (P < 0.01). In summary, RRR-PS has a significant effect on promoting blood circulation and removing blood stasis, and its mechanism of action is related to promoting angiogenesis, anti-coagulation, anti-thrombosis and anti-inflammation. The efficacy is related to the change of solvent system and the large dissolution of catechin, emodin, chrysophanol and physcion after the RRR-PS combination. The results of the study can further provide a reference for the follow-up study on the active substances and mechanism of the RRR-PS combination. Animal experiments have been approved by the Experimental Animal Committee of Shaanxi University of Traditional Chinese Medicine (No. SUCMDL20210309002).

Sturgeon cartilage has a wide range of applications as it is rich in biologically active substances such as chondroitin sulphate and protein. In this study, the safety evaluation of sturgeon cartilage peptide in NIH/3T3 and C2C12 cells was conducted, and the results showed that sturgeon cartilage peptide did not induce apoptosis and necrosis in NIH/3T3 and C2C12 cells compared to the blank control, which provides an in vitro experimental basis for the transdermal drug delivery of sturgeon cartilage peptide. Further evaluation of the scavenging activity of sturgeon cartilage peptides against the 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radicals showed that sturgeon cartilage peptides have strong antioxidant activity. A stable sturgeon cartilage peptide ointment containing 7% sturgeon cartilage peptide was prepared and analysed for its transdermal absorption in mouse skin. This experiment was approved by the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: 00007684). It was found that the 12-hour cumulative release of sturgeon cartilage peptide ointment reached 92%. In this study, we further analyzed the ability of sturgeon cartilage peptide ointment to inhibit ear swelling in mice after xylene-induced inflammation. The sturgeon cartilage peptide ointment showed significant anti-inflammatory activity compared to the matrix group and the control group. In conclusion, the present study clearly demonstrated that sturgeon cartilage peptide has good safety and antioxidant activity, and the prepared sturgeon cartilage peptide ointment provides an experimental basis for further application of sturgeon cartilage peptide as well as the study of transdermal drug delivery.

Given the vital role of vasculature in solid tumors, the potential of vascular disrupting therapy in the treatment of triple-negative breast cancer (TNBC) is promising. In this study, we prepared the acid-sensitive liposome PPD/CA4P/Lip-Rap loaded with the vascular disrupting agent CA4P and the anti-angiogenic drug rapamycin (Rap) to explore the potential of the vascular disrupting strategy in TNBC. PPD/CA4P/Lip-Rap was characterized by ¹H NMR, dynamic light scattering, and transmission electron microscopy. Its drug loading and acid sensitivity were determined. The particle size of PPD/CA4P/Lip-Rap is 161.53 ± 1.89 nm, the zeta potential is -20.03 ± 0.9 mV and it demonstrated good drug release on acidic sensitivity responses. CCK-8 experiments proved that Rap can enhance the ability of CA4P to destroy tumor vascular endothelial cells. Rap can kill marginal residual tumor cells, suppress tumor recurrence. Nanocarriers can further enhance the therapeutic effect. Western blot (WB) showed that Rap decreased the expression of hypoxia-inducible factor-1α (HIF-1α) via the mTOR/p70S6K and mTOR/4E-BP1 pathways. Thus, tumor hypoxia activation and angiogenesis were inhibited. PPD/CA4P/Lip-Rap can effectively destroy tumor vessels, inhibit tumor angiogenesis and recurrence, and provide a new strategy for the treatment of TNBC by targeting disruption of tumor vessels.

Photodynamic therapy is an emerging cancer therapy with clinical prospects, which plays a specific role in the tumor site and causes less harm to the human body. However, the toxicity of small molecules of hydrophobic photosensitizer, the tumor hypoxia microenvironment, and the biodegradability of nano-carrier systems affect its antitumor efficacy and metabolic clearance in vivo. In this paper, hexachloroplatinic acid was used as a novel oxidizing agent to initiate oxidative polymerization of pyrrole/amino pyrrole to achieve the amino functionalization; further reduced platinum acid anion in the nanostructures into platinum nanoclusters by sodium borohydride as a reducing agent to fabricate platinum nanocluster-doped polypyrrole nanoparticles (PtPPy); and finally, this functional nanoparticles delivering meso-tetra (4-carboxyphenyl) porphine (TCPP) were obtained by amide-bonded coupling of photosensitizers TCPP drug (PtPPy@T). The nanomedicine had a spherical structure, uniform morphology, a particle size of 91.93 ± 13.45 nm, and a zeta potential of -18.39 ± 1.4 mV. Experiments demonstrated that PtPPy@T could react with hydrogen peroxide overexpressed in the tumor to generate a large amount of oxygen, which could relieve the tumor hypoxia microenvironment, and at the same time, provided a sufficient substrate for the subsequent PDT; using 658 nm laser irradiation, the photodynamic effect of PtPPy@T was activated, which catalyzed the conversion of oxygen to singlet oxygen, thus triggering oxidative damage and inducing apoptosis in tumor cells; experimental studies showed that the PtPPy@T nanomedicine had a better tumor inhibitory effect in vivo and in vitro. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Radiological Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College (IRM/2-IACUC-2312-006).

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial A. senticosus samples based on atpI and atpB_rbcL according to the previous chloroplast genome sequencing results, and determinated the content of syringin by HPLC to evaluated the quality of commercial samples. A total of 80 A. senticosus samples were collected from 47 cities in 24 provinces. DNA was extracted to amplify the products of atpI and atpB_rbcL by PCR. The results showed that 7 haplotypes (H2, H5, H8, H10, H12, H14, H23) were formed by the combined analysis of the two gene fragments. H2 from Yichun in Heilongjiang, Shangzhi in Harbin, Suihua in Heilongjiang, Fushun in Liaoning, Benxi in Liaoning, Changbai in Jilin and Jingyu in Jilin were the dominant genotype, representing 58.75% of the total samples. H14 and H23 were the unique haplotypes of the producing area. It is speculated that the commercial A. senticosus samples with haplotypes of H14 and H23 are from Raohe, Shuangyashan, Heilongjiang and Mingshui, Suihua, Heilongjiang, respectively. HPLC analysis indicated that the content of syringin in 73.96% of the samples met the Pharmacopoeia standards. There was a significant difference in the content of syringin among the samples, ranging from 0.003 7% to 0.524 5%, with a difference of 0.520 8%, indicating that the quality of the samples in the market of A. senticosus was uneven. However, there were no significant differences in the contents of syringin in the commercial A. senticosus among different haplotypes. The content of syringin in the haplotype H23 in the market sample is relatively high, so it may be a germplasm with better quality. This study researched the germplasm resources and medicinal materials quality of commercial A. senticosus samples and will help guide the commercial circulation, reasonable medication of A. senticosus, and the screening of excellent germplasm.