Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses.

Antibacterial therapy is a global health issue. The antibiotic resistance is becoming an increasingly serious threat, which caused by misuse and overuse of antibacterial agents combined with the emergence of new resistance mechanism. The resulting infection treatment risk and incidence of the spread of disease, severe cases and deaths are increased in different degrees. With the extensive application of biomaterials and nanotechnology to biomedicine, extensive research has been conducted on antibacterial infection. With the specific physicochemical properties like optical, electric and magnetic and high penetration, inorganic nanomaterials can produce natural antibacterial effect. Nanomedicine can be designed to allow controlled drug release and targeting effect, thus demonstrated better antibacterial efficiency. In this review, the mechanism of antibacterial resistance is described, and the antibacterial infection research on inorganic nanomaterials, as well as nano-drug delivery system including liposomes, nanoparticles, dendrimers and biomimetic nanocarriers are summarized. Nanomaterials and nanotechnology offer promising strategies for the development of new agents that can improve efficacy on antibacterial infections and overcome antibiotic resistance potentially.

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

Thirteen isoflavones were separated and purified from an ethanol extract of the rhizome of Dalbergia benthamii Prain by using silica gel, Sephadex LH-20, recrystallization et al. Their structures were identified by physicochemical properties and spectral analysis such as MS, 1D/2D-NMR as dalbergibenthamin (1), butesuperin A (2), xanthocercin A (3), butesuperin B (4), di-O-methylalpinum isoflavone (5), 2′-deoxgisoaunculutin (6), robustone (7), 4′-hydroxy-5, 7-dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (8), formononetin (9), 6″-O-rhamnosyldaidzin (10), 3′, 4′-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (11), derrubone dimethyl enter (12), and derrubone (13). Compound 1 is a pair of new isoflavonoid enantiomers, compound 12 is a new natural product and compounds 1-7 and 10-13 were obtained from D. benthamii Prain for the first time. In vitro cytotoxic activities of the compounds were explored by MTS testing with HL-60, A-549, SMMC-7721, MCF-7 and SW480 cell lines. Results show that compound 8 significantly inhibited cellular proliferation. The IC₅₀ of compound 8 in A-549 and SW480 cells was 16.68 ± 0.19 and 15.21 ± 0.60 μmol·L^-1.

Based on ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), a rapid and simultaneous quantitative method for the measurement of seven components (kinsenoside; rutin; kaempferol-3-O-rutinoside; quercimeritrin; narcissin; isorhamnetin-3-O-glucoside; quercetin) of A. roxburghii was established. The separation was performed over 8.0 minutes on a Waters Acquity UPLC BEH Shield RP18 (2.1 mm×100 mm; 1.7 μm) with a mobile phase consisting of acetonitrile (A) and 0.1% formic acid water solution (B) with gradient elution at a flow rate of 0.2 mL·min^-1; the column temperature was 30℃ and the injection volume was 2 μL. Electrospray spray ionization source (ESI source) was used for mass spectrometry, and positive and negative ion modes were detected at the same time. The results showed good linearity (R² ≥ 0.998 0), with good precision, repeatability and stability, and the average recovery was 97.71%-103.33%. Through cluster heat map and redundancy analysis, we found that kinsenoside was mainly distributed in stems, followed by leaves, and the lowest content in roots. The content of kinsenoside increased significantly in the stems of plants 6 months, but less change was evident in the roots and leaves. Flavonoids and flavonoid glycosides were mainly distributed in leaves. The UHPLC-MS/MS method established in this paper can be used for the quality control of A. roxburghii and provides a reference for establishing a more comprehensive quality detection method for this medicinal.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a new imaging technique with label-free, rapid, and high throughput features. It has bloomed in the analysis on the spatial distribution of biomolecules such as drugs, metabolites, peptides and proteins on the tissue surface in virtue of providing high data throughput from non-targeted full analysis and high accuracy from targeted analysis. The acquisition of MSI signal response with high sensitivity, high spatial resolution, and good stability is directly depended on the appropriate sample preparation approaches, and flexible and various data processing tools will help the non-target data mining to meet the demands of visualization, spatial distribution and multiple index applications so as to reveal the scientific rules beneath the data. This review briefly summarizes the key advances in MALDI-MSI from aspects of sample preparation procedures, data processing and visualization. It also illustrates the characteristics, difficulties and probable solutions derived from these key techniques.

It is of great significance to apply the nanocrystals self-stabilized Pickering emulsion (NSSPE) to traditional Chinese medicine (TCM) compounds, and to study the effect of NSSPE on the oral absorption of various components with different solubility and permeability. In the study, NSSPE of Tongmai prescription was prepared by the high pressure homogenization method with nanocrystals of main active components (puerarin, ferulic acid, salvianolic acid B and tanshinone IIA) of Tongmai prescription as solid particle stabilizers and a mixture of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS as oil phase. The NSSPE had better physical stability than nanocrystals suspension and blank emulsion. The adsorption of nanocrystals on the surface of oil droplets was confirmed by scanning electron microscopy and fluorescence microscopy. The surface adsorption rates of puerarin, ferulic acid, salvianolic acid B and tanshinone ⅡA in NSSPE were 15.40% ±3.19%, 15.39% ±5.07%, 10.97% ±3.70% and 31.51% ±1.60%, respectively. When solid active components were prepared into nanocrystals suspension, the cellular uptake and transport across Caco-2 cells were increased significantly for puerarin and tanshinone IIA. The uptake rates of ferulic acid, ligustilide and tanshinone IIA in NSSPE were further increased compared with the physical mixture of nanocrystals suspension and oil, and the transports of ligustilide and tanshinone IIA were also significantly improved. The main absorption mechanisms of NSSPE were passive diffusion and caveolin-mediated endocytosis, which were determined mainly by the microstructure of NSSPE. In conclusion, NSSPE could be applied to complicated TCM. The "micro" and "nano" synergistic microstructure with drug nanocrystals adsorbed on the surface of micron-sized oil droplets could not only improve the physical stability of NSSPE, but also promote the absorption of various components in NSSPE, which made NSSPE a promising oral drug delivery system for TCM.

Juvenile zebrafish were used to screen the active components of Lycii Fructus for improving osteoporosis. The screening results were further verified by zebrafish adult osteoporosis model and the action mechanism was explored. Prednisolone was used as the inducer to build osteoporosis models of juvenile and adult zebrafish, and 9 groups of samples of different extracts and chemical parts of Lycii Fructus were given. Alizarin red staining was applied for observing the scale matrix mineralization and bone resorption. The activities of osteoblasts and osteoclasts were detected using alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP/TRACP) staining. The expressions of bone metabolism-related genes alp, osteoprotectin (opn), osteoblast specific transcription factor (sp7), cathepsin K (ctsk), tracp, and Runt family transcription factor 2b (runx2b) in each group were determined using quantitative polymerase chain reaction. The results showed that all components of Lycii Fructus improved the formation area of the first vertebrae, the staining light density value, and the number of vertebrae joints in juvenile zebrafish and the Lycium barbarum polysaccharide (LBP) treatment group exerted the best effect. In addition, LBP prevented the formation of bone resorption lacunae in zebrafish scales, increased ALP activity, decreased TRAP activity, up-regulated the alp, sp7, and opn genes, and lowered the expressions of ctsk and tracp genes. In conclusion, LBP regulated the activity of osteoblasts and osteoclasts, reduced bone resorption, promoted bone formation and enhanced bone density, which might be the main anti-osteoporosis active fraction of Lycii Fructus. This study provided modern scientific evidence for the scientific connotation of the traditional effect of "strengthening bones and muscles" of Lycii Fructus, provided the reference for the evaluation of the anti-osteoporosis activity of traditional Chinese medicine based on zebrafish adult model, and provided beneficial enlightenment for the bone health needs of the aging society population.

Polymer self-healing is mainly based on the molecular structure and interaction of polymers, and some need external stimulation, such as light, heat, pH, etc. In recent years, many studies have found that the self-healing properties of polymers can prolong the life of materials, while maintaining the mechanical properties of polymers after healing. According to the different action modes of polymer materials, it can be divided into autonomous self-healing and non-autonomous self-healing. Among them, autonomous self-healing mainly works through reversible covalent bonds (Schiff base bond, Diels-Alder reaction, hydrazide bond), reversible non-covalent bonds (hydrogen bond, metal-ligand coordination bond, electrostatic interaction, π-π stacking interaction, hydrophobic interaction) and a combination of the two interactions. Drug carriers with unique self-healing properties play an important role in the encapsulation and stable release of biomacromolecules. In this review, the self-healing mechanism of polymers and their applications in the field of biomedicine were briefly summarized and discussed.

Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.