In order to explore the genetic diversity and structure of Bupleurum chinense, we used 18 pairs of SSR molecular markers to analyze the genetic diversity of 619 individuals in 62 cultivated and wild populations of Bupleurum chinense from Shanxi and the surrounding provinces. The results show that the 62 Bupleurum chinense populations have high genetic diversity, with that of the wild Bupleurum chinense populations greater than that of cultivated populations. AMOVA analysis indicated that genetic variation within populations was greater than between populations. Principal coordinate analysis (PCoA) divided the Bupleurum chinense populations into 3 groups, the first group containing wild Bupleurum chinense populations from all parts of Shanxi, the second group consisting of cultivated Bupleurum chinense populations from Shanxi, Hebei, Shaanxi and Liaoning, and the third group consisting of cultivated Bupleurum chinense from Shanxi and Gansu. STRUCTURE software cluster genetic structure analysis grouped the 62 Bupleurum chinense into two populations: the first group composition was the same as the population classified as the third category in the PCoA analysis, while the second group includes the populations from the first and second categories of the PCoA. PCoA, cluster genetic structure analysis, and NJ tree cluster all gather wild Bupleurum chinense population into a single category, distinguishing it from the cultivated populations. This study provides a theoretical basis for the utilization of germplasm resources, genetic variation and the development of quality germplasm resources for Bupleurum chinense.

Sesterterpenoids, composed of five isoprene units and biosynthetically derived from geranylfarnesyl diphosphate (GFDP), are a class of the precious terpenoids with approximately 1 300 natural products known to date. Natural sesterterpenoids are widely distributed and possess extreme structural complexity and diversity and remarkable biological activity. In recent decades, a series of important progresses have been made in sesterterpenoid biosynthesis with the development of genome mining and heterogeneous expression technologies. This paper mainly focuses on the advances in sesterterpenoid biosynthesis, including the biochemical functions and catalytic mechanisms of GFDP synthases, sesterterpene synthases and oxidases. This review would lay the foundation for in-depth investigation on the biosynthesis, biological activities and synthetic biology of sesterterpenoids.

Lornoxicam (LOR) is a nonsteroidal anti-inflammatory drug with analgesic, anti-inflammatory and antipyretic effects. As a biopharmaceutics classification system (BCS) class Ⅱ drug, it has poor aqueous solubility and then low bioavailability after oral administration. In addition, the tabletability of LOR itself is also poor and could not form the tablet after compression, which seriously limits the development of its oral solid dosage. The current study aims to improve dissolution and tabletability of LOR by cocrystallization technique with small molecule puerarin (PUE). LOR cocrystal with the co-former PUE was prepared via the solvent-evaporation method and characterized by powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and thermo-gravimetric analyzer. The dissolution behavior, tabletability and stability of the prepared cocrystal were also further investigated. In comparison to pure LOR, LOR-PUE cocrystal showed higher apparent and intrinsic dissolution rate. Moreover, after cocrystallization, the solubility of LOR and PUE showed 4.0-fold and 1.5-fold increase compared to the raw ones in water, respectively. LOR-PUE cocrystal showed significantly improved tabletability compared to LOR alone under a wide compression range of 75-375 MPa. In addition, such cocrystal exhibited superior chemical stability with no change of drug contents for at least 60 days under the conditions of 40 ℃ and 25 ℃/75% RH.

α3β4 nicotinic acetylcholine receptors (nAChRs) are potential therapeutic targets in diseases such as addiction, cancer, and obesity. In this study, by replacing three amino acids of the α3 subunit with the corresponding positions of the rα6 subunit simultaneously, an α3[K152E, E184D, Q195T] subunit mutant was constructed by PCR-mediated site-directed mutagenesis and its cRNA was obtained by in vitro transcription. The cRNA of mutant subunits mixed in equal molar ratios with β4 subunits were microinjected into Xenopus oocytes. The pharmacological activity and function of α3[K152E, E184D, Q195T]β4 nAChR was evaluated by a two-electrode voltage clamp electrophysiological technique. Acetylcholine, nicotine, and cytisine were used as agonists to evaluate the magnitude of ligand-gated currents and gating characteristics of wild-type and mutant α3β4 nAChRs. The half-maximal effective concentrations (EC₅₀) of acetylcholine, nicotine, and cytisine on wild-type α3β4 nAChRs were 277.5, 34.02 and 23.05 µmol·L^-1, respectively, while their EC₅₀ values with α3[K152E, E184D, Q195T]β4 nAChR were 170.5, 26.6, and 98.45 µmol·L^-1, respectively. Thus these EC₅₀ values for the three agonists towards the mutant receptor were changed 0.6-fold, 0.8-fold, and 4.3-fold, respectively, compared with the wild-type receptor; cytisine was most strongly affected, with a 77% decrease in potency. However, the maximum agonistic efficiency (E_max) of cytisine on wild-type and mutant α3β4 nAChRs was increased from 94.12% to 155.08% relative to the peak current amplitude induced by 1 mmol·L^-1 acetylcholine. Thus, although the α3[K152E, E184D, Q195T]β4 nAChR had significantly reduced sensitivity to cytisine, the maximum current amplitude induced by cytisine was clearly increased. This mutant had slightly increased sensitivity to acetylcholine and nicotine. The results indicate that these three amino acids of the α3 subunit have important and varying effects on ligand binding to the α3β4 nAChR, providing a basis for further structure-functional research on α3β4 nAChR, as well as the pathology of related diseases.

The emergence of antibiotic-resistant strains seriously reduces the efficiency of traditional antibiotic therapy. The development of a new alternative antibiotic method to effectively eliminate this bacterial infection has become a critical issue. Photothermal therapy (PTT) has shown many advantages in tissue penetration, spatiotemporal specificity, no drug resistance and broad-spectrum antimicrobial ability. However, extremely high temperature (55-65 ℃) is needed to achieve highly efficient bactericidal effect during PTT treatment process. Thus, this procedure will inevitably cause collateral damage to normal tissues. Silver nanoparticles (AgNPs) are one of the most commonly used broad-spectrum antimicrobial agents. Its antimicrobial activity is mainly derived from the release of silver ions (Ag⁺). However, excessive AgNPs not only would cause toxic to the body, but also waste precious metals. In this study, oxidized mesoporous carbon nanospheres (OMCN) were used as photothermal materials to prepare OMCN-Ag⁺ composites. The composite material can improve the antibacterial activity, reduce the waste of metal Ag and decrease the toxic and side effects. Moreover, the precisely controlled mild heat can overcome the shortcoming such as the damage to normal tissue caused by the excessive temperature during traditional photothermal antimicrobial process. The antimicrobial treatment system exhibits a good biocompatibility both in vitro and in vivo. Specially, the designed nanosytem can effectively eliminate the bacteria from the infected wound, subsequently promoting the process of wound healing. All animal experiments were carried out with approval of the Animal Experiment Ethics Committee of Henan University.

Silk fibroin is a kind of natural biodegradable polymer, which is stable, non-toxic, cheap and easy to obtain, and has no inflammatory reaction. Silk fibroin shows satisfactory degradability and biocompatibility, widely used as a promising material for biological tissue engineering and drug delivery carrier in the biomedical field. This review introduces the structure and constituent of silk fibroin, summarizes the research progress and methods of evaluating biodegradability and biocompatibility in vivo and in vitro, which provides reference for further research and application of silk fibroin.

Totally 28 new 12N-substituted aloperine derivatives were designed, synthesized and evaluated for their down-regulating PD-L1 activities in breast cancer MDA-MB-231 cells. Among them, compound 7f could significantly down-regulate PD-L1 level in concentration- and time-dependent manners, and exhibit a low cytotoxicity. It activated the killing activity of co-cultured T cells against tumor cells in a concentration-dependent manner, showing the potential of tumor immunotherapy. Further study indicated that 7f mediated the degradation of PD-L1 through a lysosomal pathway. This study provides useful guidance for the development of aloperine compounds into new small molecule tumor immune suppressants.

Tuberculosis (TB) is an enduring threat to global health. The epidemic persists with growing drug resistance, especially for extensively drug-resistant TB. Therefore, the treatment for TB and its associated multidrug resistance has been an ongoing challenge. Due to the greater attention and investment in the elimination of this disease, significant progress has been achieved. Bedaquiline, delamanid, and pretomanid have been approved for the clinical use. In addition, two dozens new anti-TB drugs are currently in clinical testing. China has contributed four new drugs TBI-223, TBI-166, aulimanid, and WX-081. The aim of this review is to summarize the recent advances in anti-TB drug development. Based on the different clinical stages of these anti-TB drugs, we mainly focus on mechanism of action, in vitro and in vivo pharmacological studies, pharmacokinetics and clinical studies.

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

The crude Et₂O extract of soft coral Sarcophyton glaucum, collected off the Xisha, the South China Sea, were investigated. A new cembrane-type diterpenoid, namely 15-dehydroxy-sarcophytrol D (1), together with twenty-five known compounds, namely ximaoglaucumin C (2), (11S, 12S, 1E, 3E, 7E)-11, 12-epoxycembra-1, 3, 7-triene (3), sarcophytol W (4), cembrene (5), sarcophytol B (6), sarcophytol K (7), sarcophytol J (8), pentaene-cembrene (9), sarcophytol E (10), (+)-marasol (11), (2S)-sarcophytoninsarcophytoxide (12), (-)-17-hydroxydeepoxysarcophytoxide (13), (+)-sarcophytoxide (14), 13-acetoxysarcophytoxide (15), bophynin B (16), 16-oxosarcophytoxide E (17), sarcophinone (18), 7α-8β-dihydroxydeepoxysarcophine (19), (+)-sarcophine (20), 14-dehydroxy-sarcophytol L (21), sarcophytol L (22), 13α-hydroxy-sarcophytol L (23), trocheliophol C (24), trocheliophol E (25) and trocheliophol L (26), were isolated and purified by comprehensive chromatography methods of silica gel column, Sephadex LH-20 gel column, TLC, and semi-preparative high-performance liquid chromatography (HPLC). In anti-inflammatory bioassay, compound 4 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in BV-2 microglial cells.