Natural polysaccharides with good biocompatibility and unique tumor immunomodulatory activity are becoming an important adjuvant anticancer therapy in clinic. In the field of pharmaceutics, natural polysaccharides can be used as not only bioactive components but also drug delivery carriers, as well as tumor-targeted ligands. Besides, various novel drug delivery systems based on natural polysaccharides exhibit unique advantages in regulating tumor immune microenvironment. In this review, we summarize the progress on natural polysaccharides in tumor microenvironment (TME) regulation and the designs of nano-sized drug delivery system, and point out challenges of polysaccharide-based drug delivery systems in the future application, and also give the potential solutions for these issues.

Single cell "omics" technology enables the capture of genome, transcriptome, proteome and other omics information in a high-throughput and unbiased manner at single-cell resolution, allowing the characterization of the functional state of individual cells to reveal their heterogeneity and differential responses to drug treatment. This technology has wide application in pharmacological research, facilitating drug screening, efficacy evaluation, and mechanistic studies. We envision that, in the field of traditional Chinese medicine (TCM), single cell omics technology can be applied in the identification of active ingredients and drug targets, and elucidation of drug mechanism of action. In this article, we briefly introduce the single cell omics technology - particularly single cell transcriptome sequencing, and review its application in the field of modern drug research. Based on that, we propose the concept of "single cell pharmacology" and articulate how it can be applied to transform the pharmacological research of TCM and promote TCM modernization.

Plant natural products (PNPs) are important sources of innovative drugs. They are mainly obtained by isolation or extraction from plants. Low content and with structural analogues in plants result in high production cost, which restricts the research and application of PNPs. While biopathway construction by synthetic biology provides an alternative for production of PNPs. By biosynthetic pathway analysis of PNPs and reconstructing the biopathway in microorganisms, we can produce PNPs in cell factories efficiently. Recently, several predominantly international reports about biosynthesis of PNPs and its synthetic biology production, triggered the researches of PNPs. Abundant traditional Chinese medicine resources and profound cultural heritage of Chinese medicine make biosynthesis pathway analysis of PNPs to be a research hotspot. And some of the studies have achieved significant progress. Here, recent progress in the biosynthesis of plant natural products and its synthetic biology was reviewed. In particular, the application of new methods and technologies in recent years were summarized and discussed. This will provide reference for the biopathway construction of plant natural products.

Twenty compounds were isolated and purified from the fresh roots of Huaizhong NO.1 Rehmannia glutinosa by various chromatographic techniques such as Toyopreal HW-40C, Sephadex LH-20, silica gel and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 3-methyl-2-(hydroxymethyl)-4H-pyrone-4-one (1), 3-amino-2-pyridine ethanol (2), (5'S)-2-oxo-N-phenylpyrrolidine-3-carboxamide (3), L-pyroglutamic acid methyl ester (4), indazole (5), uridine (6), adenosine (7), rehmanalkaloid C (8), 1-(3-ethylphenyl)-1, 2-ethanediol (9), (3-ethylphenyl)-1, 2-ethanediol (10), 2-hydroxymethylphenyl-1-O-β-D-glucopyranoside (11), mussaenoside (12), 11-methylforsythide (13), 7-deoxygardoside (14), 1-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopyranoside (15), 6-deoxy-D-mannono-1, 4-lactone (16), monoethylfumarate (17), daphneresinol (18), dihydroquercetin (19), rhamnopyranosyl vaniloyl (20). Compound 1 is a new compound, named as 3-methyl-2-(hydroxymethyl)-4H-pyrone-4-one, compounds 2 and 3 are new natural products, and compounds 4, 5, 9-11, 13, 14 and 16-19 are isolated from Rehmannia for the first time.

The plant-specific WRKY transcription factor family is involved in the regulation of the response of plants to various environmental factors and biological stress. To study the role of the BcWRKY70 gene in Bupleurum chinense DC., we cloned the open reading frame (ORF) sequence of the BcWRKY70 gene based on the transcriptome database. Bioinformatics analysis of BcWRKY70 and promoter region analysis was carried out, and real-time qRT-PCR was used to detect the expression pattern of BcWRKY70 in different tissues and under the different hormone treatments. The results show that the BcWRKY70 ORF is 948 bp in length, encoding 316 amino acids with a typical WRKY domain. Phylogenetic analysis showed that BcWRKY70 is closely related to GhWRKY70. Its promoter region contains cis-elements that presumably respond to environmental factors such as drought, methyl jasmonic acid (MeJA), and abscisic acid (ABA). qRT-PCR analyses showed that BcWRKY70 is most highly expressed in roots and can quickly respond to MeJA and ABA induction. This study provides a basis for further research on the molecular mechanism of BcWRKY70 in B. chinense DC. resistance.

A model for quality evaluation was developed by determination of multi-index components in Scutellaria baicalensis Georgi. Eight flavonoids in Scutellaria baicalensis Georgi were quantified by high performance liquid chromatography (HPLC), and a quantitative analysis of multi-components with a single marker (QAMS) method with baicalin as the internal reference substance was established. The 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS⁺) method was applied to determine the antioxidant activity of different batches of Scutellaria baicalensis Georgi. Grey relevance analysis was conducted to calculate the grey correlation coefficients of each antioxidant in the herb. The holistic quality of 75 batches of collected samples from different product regions was evaluated to distinguish different commercial types of Scutellaria baicalensis Georgi. The relative correction factor (RCF) of each index component with baicalin as the internal reference indicated good applicability, and there was no significant difference in assay results between the QAMS method and the external standard method (ESM). The results of grey correlation analysis showed that the content of eight index components including baicalin correlated strongly with the antioxidant activity of Scutellaria baicalensis Georgi. The calculated grey relational coefficient ranged from 0.772 4 to 0.808 6. The content of oroxylin A-7-O-β-D-glucuronide, norwogonin-7-O-β-D-glucuronide, baicalein, wogonin and oroxylin A showed positive correlations with the antioxidant potency. In contrast, baicalin, wogonoside and viscidulin Ⅲ content exhibited negative correlations. The ratio of the flavonoid glycosides and flavonoid glycoside aglycones were found to be a critical factor to distinguish the different types of commercial herbs. The crude herbs could be characterized as Scutellaria baicalensis pith-decayed with a G/A ratio less than 10, and the ratio in Scutellaria baicalensis pith-not decayed should be more than 10. The QAMS method established in this study is simple and accurate, and can be used for the determination of eight flavonoids in Scutellaria baicalensis Georgi. Combined with ABTS⁺ antioxidant activity and grey correlation analysis, a comprehensive model for Scutellaria baicalensis Georgi quality determination based on biological activity was established, which provides new ideas and methods for the establishment of quality standards consistent with the characteristics of traditional Chinese medicine.

In recent years, many biosimilars have been approved marketing authorization in our country. When conducting research and evaluation of biosimilar, the quality similarity between the candidate drugs and the original drugs is the key point of "biosimilar", meanwhile it is the basis for clinical and marketing authorization of biosimilar. However, the industry and regulatory agencies are facing many challenges in establishing quality "similarity assessment criteria", such as: limited batches of original drugs; quality drift caused by manufacture process changes in the life cycle; analytical method of critical quality attributes is different from different manfactures; statistical methods used for establishing assessment criteria are difficult to unify. In the article, the data obtained from 69 lots of chemistry, manufacturing and control (CMC) dossier of trastuzumab originator company and dossiers of 9 biosimilar companies were analyzed. Furthermore, combined with the risk identification of the critical quality attributes of the product, quality "similarity assessment criteria" have been proposed. This standard has been verified by the disclosure of biosimilar quality data, aim to promote the development and evaluation of trastuzumab biosimilar.

Liver fibrosis is a common scarring response to virtually all forms of chronic liver injury and is characterized by excessive accumulation of extracellular matrix. Excessive activation of hepatic stellate cells (HSCs) is a key step in liver fibrogenesis. The withanolide extract of Physalis angulata (WEP) is a physalin-type withanolide enriched partition from Physalis angulata. In this study, liver fibrosis mice models were established by CCl₄ and bile duct ligation (BDL) in vivo. Transforming growth factor-β1 (TGF-β1) was given in vitro to induce activation of human hepatic stellate cells LX-2 and treated with WEP at different concentrations. All animal experiments in this paper have been approved by the Ethics Committee of China Pharmaceutical University. The in vivo results showed that, compared with the CCl₄ or BDL group, WEP could reduce collagen deposition and liver damage, and reduce the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in serum. In vitro, WEP had no significant cytotoxicity to LX-2 cells, but significantly reduced the mRNA and protein expressions of fibrotic markers collagen type Ⅰ α 1 chain (COL1A1) and α-smooth muscle actin (α-SMA) and inhibited the activation of hepatic stellate cells. In addition, WEP inhibited the expression of yes-associated protein (YAP) and the phosphorylation level of Smad family member 2 (Smad2) in vivo and in vitro. In conclusion, WEP can inhibit hepatic stellate cells activation via regulating the YAP and TGF-β-Smad pathways, and shows promising anti-fibrosis activity in vitro and in vivo.

With the increasing drug resistance of bacteria, especially Gram-negative bacteria, the infection of drug-resistant bacteria has become one of the most challengeable clinical problems. The siderophore-antibiotic conjugates based on the "Trojan horse" strategy can penetrate the extracellular membrane of Gram-negative bacteria by active transport, and they are expected to become a powerful weapon for clinical anti-infection treatment. This review describes the drug design strategies of siderophore-antibiotic conjugates reported in recent years, and focuses on the use of different types of antibiotics in this strategy.

The development of mass spectrometry and proteomics significantly advanced our understanding of post-translational methylation of proteins. In recent years, a large number of proteins containing the methylation recognition domain have been identified. Protein methylation mainly occurs on lysine and arginine residues. Both lysine and arginine have three different methylation states. Lysine can be mono-methylated, di-methylated, and tri-methylated, while the arginine residue can be modified as mono-methylation, symmetrical di-methylation, and asymmetrical di-methylation. Methylation recognition domains can accurately identify lysine or arginine with different state of methylation, transfer methylation signals, and perform functions in a variety of cellular processes, including gene expression regulation, RNA splicing and translation, cell cycle regulation, etc. In recent years, researchers have found that the abnormalities of these recognition proteins are also closely related to the genesis and development of tumors. Therefore, these methylation recognition proteins were considered as potential drug targets for small molecule intervention. In this review, we summarized the researches on the recognition domains of protein methylation as well as their inhibitors, hoping to provide the basis for further drug development in this field.