With the increasing severity of bacterial resistance issues, β-lactamase, as the key enzyme mediating resistance to β-lactam antibiotics, requires rapid and accurate detection that plays significant importance for clinical treatment and antimicrobial resistance surveillance. In recent years, the rapid development of proteomic technologies has provided novel strategies for high-throughput identification of β-lactamases. This article reviews the application progress of mass spectrometry-based proteomic technologies in β-lactamase detection, compared with traditional phenotypic detection and genetic sequencing methods, proteomic technologies enable direct capture of enzyme expression-level information, offering multidimensional data support for elucidating the association between resistant phenotypes and protein functions. Furthermore, advancements in targeted proteomics have enhanced detection sensitivity and specificity, facilitating the exploration of personalized anti-infective therapies. Looking forward, through the integration of artificial intelligence-assisted analysis and the development of miniaturized high-throughput detection devices, proteomic technologies are expected to play a more prominent role in real-time antimicrobial resistance monitoring and precision medicine.

Conventional antibody discovery paradigms mainly rely on animal immunization and hybridoma screening, which results in long development lead times, high costs, and a low success rate for antibody therapeutics. Recently, artificial intelligence (AI) is constantly driving the progress of antibody drug research and development technology with advantages in large-scale proteomic data processing. It plays a great important role in the prediction of antibody structure and de novo generation of target-specific sequences, which also substantially enhances the hit rate of drug candidates. Therefore, this article aims to summarize recent developments and challenges in the application of AI technology to antibody discovery and design, while also considering the limitations to traditional methodologies. Hope to provide practical guidance for AI-driven antibody drug development.

QS-21 is an immunologically active saponin-based immunostimulant extracted from the bark of the South American soapbark tree (Quillaja saponaria, QS). It consists of four structural domains: Quillaic acid, a trisaccharide side chain, a tetrasaccharide chain, and a pseudodimeric acyl chain. It exists in two isomeric forms, QS-21-Api and QS-21-Xyl, among which the C-4 aldehyde group and the acyl side chain are the key moieties for adjuvant activity. In terms of its immunological mechanism, QS-21 can simultaneously activate Th1/Th2-type immune responses, enhance the cross-presentation of antigens by dendritic cells, and activate the MAPK (mitogen-activated protein kinase) pathway in T cells as well as the NLRP3 (NOD-like receptor protein 3) inflammasome. It exhibits particularly prominent performance in inducing cellular immunity. This article summarizes the currently developed composite adjuvant systems such as AS01, AS02, Matrix-M, AS15, and GLA-LSQ, along with their applications in vaccines including the malaria vaccine Mosquirix and the shingles vaccine Shingrix. Regarding issues such as supply shortages associated with natural extraction, technologies for chemical total synthesis, semi-synthesis, and yeast-based biosynthesis are making gradual breakthroughs, Strategies including some derivatives (such as VSA-1 and TQL1055) also provide references for the development of new vaccines and the prevention and control of infectious diseases as well as immunotherapy.

As indispensable medications in the medical field, antibiotics face severe challenges such as high pollution and high energy consumption in their traditional chemical synthesis processes. The novel enzymatic catalytic process, leveraging the catalytic properties of enzymes and the advantages of environmental friendliness, has emerged as a new direction for the green development of the antibiotic industry. This paper focuses on the application progress of the novel enzymatic catalytic process in the green synthesis of antibiotics, systematically elaborates on its catalytic mechanism, and analyzes the specific applications and advantages of this process in the production of antibiotics such as β-lactams, aminoglycosides, and macrolides. Meanwhile, it points out the issue that catalyst residues during the production process affect the quality and safety of pharmaceutical products, and discusses the current challenges confronted by the novel enzymatic catalytic process for antibiotics. Finally, by applying cutting-edge technologies including synthetic biology and artificial intelligence, this paper provides a theoretical basis and solutions for breaking through existing technical limitations and promoting the green upgrading of the antibiotic industry.

The elusive in vivo fate of nanomedicines represents a critical barrier to their clinical translation. Recent rapid advancements in imaging technologies, such as fluorescence imaging (FLI), photoacoustic imaging (PAI), radionuclide imaging (RI), magnetic resonance imaging (MRI), and multimodal imaging (MI) have provided powerful tools for real-time and in situ analysis of nanomedicine behavior in vivo, encompassing morphological evolution, drug release kinetics, distribution, metabolic and so on. However, significant challenges persist, particularly in continuously tracking dynamic morphological changes throughout their entire lifecycle and achieving accurate quantitative analysis within the physiological microenvironment. This review focuses on recent progress in understanding the in vivo fate of nanomedicines, systematically summarizing the fundamental principles, applications, advantages and limitations of these imaging technologies. It also highlights recent breakthroughs in utilizing these technologies to decipher the in vivo fate of nanomedicines and explores future perspectives, such as the development of innovative probes and the integration of multimodal imaging platforms. The objective is to offer robust theoretical and technical foundations for optimizing the design of nanodrug delivery systems and promoting their clinical translation.

The current quality control standards for traditional Chinese medicine (TCM) are relatively simplistic, as relying solely on the quantification of chemical components fails to fully interpret the quality connotation of multi-effect medicinal substances. In contrast, phase-state analysis, which focuses on the physical forms of multiple components, is considered to provide a new perspective for researching the material basis of the efficacy of TCM. This article focuses on the challenges in quality control of multi-efficacy TCM, systematically analyzes the limitations of current standards in reflecting its multi-functional nature, and reviews research approaches and current progress on the role of physicochemical state in the material basis of TCM efficacy. It elaborates on the mechanism of self-assembly via non-covalent bonds and the structure-function synergy. Building on this, a new "top-down and bottom-up" integrated strategy for quality control research of multi-efficacy TCM is proposed. This aims to promote innovation in TCM quality control models, guide rational drug selection, and provide a scientific basis for constructing a quality evaluation system that aligns with the characteristics of TCM.

Bacterial and parasitic infections rank as the second leading cause of death globally. The persistent rise in antibiotic resistance, particularly against β-lactams, vancomycinand methicillin, poses a significant challenge to public health. The World Health Organization (WHO) has prioritized the fight against antibiotic resistance, recognizing the urgent need for new targets and the development of novel antibiotics. Given that many potential drugs focus on pathogens prioritized by the WHO, which often share characteristics with existing antibiotic classes, fostering resistance, there is an imperative requirement to identify new targets and develop agents that specifically address these challenges. Bacterial peptidoglycan, with its specificity for bacteria and essential role in their survival, has become a focal point of research. Due to the enzymes involved in peptidoglycan biosynthesis being exclusive to bacteria, they represent ideal targets for the discovery of new antimicrobials. Inhibiting these enzymes offers an optimal inhibition profile, where the inhibitors are inactive towards eukaryotic cells but effectively combat bacterial infections. The aim of this review is to introduce the advancements in the synthesis of a series of inhibitors targeting the bacterial transferase MraY, which catalyzes the first membrane-bound step in peptidoglycan biosynthesis. Currently, there are no antibiotics in clinical use that target MraY. By inhibiting MraY, the hope is to mitigate the development of resistance. Natural inhibitors of MraY, based on the aminoarabinosyluridine scaffold, have been known for their biological activity. However, due to their limited antibacterial efficacy, several research groups have embarked on the development of simplified analogues to enhance their therapeutic potential.

The aim of this study is to elucidate the mechanism of metadoxine through which it attenuates alcoholic liver disease-associated hepatic steatosis. In this study, the effect of metadoxine on alcoholic liver disease was evaluated in mouse model of alcoholic liver disease induced by high alcohol and high fat diets. In addition, RNA sequencing (RNA-Seq) of the liver tissues was applied to determine the dominant signaling pathways in response to metadoxine treatment. The mechanism of metadoxine on metabolic was investigated by mitochondrial function in HepG2 cells. The animal experiments in this study were conducted in accordance with the guidelines of the Ethics Committee for Scientific Research of Hefei University of Technology and were approved by the Animal Experiment Ethics Committee (approval No.: HUFT20210615002). When mice were fed a diet designed to induce alcoholic liver disease, hepatic lipid accumulation resulted. In this study, the level of serum biomarkers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), was substantially decreased in mice treated with metadoxine compared to the model group (P < 0.05). Meanwhile, the inflammatory infiltration and steatosis in liver were alleviated by the administration of metadoxine compared to the model group (P < 0.01). In vitro, metadoxine significantly reversed ethanol overload-induced impairment of mitochondrial respiratory function and increased mitochondrial membrane potential in hepatocytes. Transcriptomic sequencing (RNA-Seq) analysis of liver tissue identified significant enrichment of the mitogen-activated protein kinase (MAPK) signaling pathway. Measurement of MAPK phosphorylation levels in liver tissue showed that metadoxine treatment significantly reduced MAPK phosphorylation (P < 0.01). Furthermore, the protective effects of metadoxine were abolished upon co-treatment with a p38-MAPK inhibitor. Conversely, co-treatment with a p38-MAPK activator reversed the inhibitory effect of metadoxine on p38-MAPK phosphorylation. This study investigated the mechanism of metadoxine in alcoholic liver disease and found that metadoxine enhanced mitochondrial function by the phosphorylation of MAPK and reduced the lipid accumulation and inflammation in alcoholic liver disease.

By comprehensively applying various separation techniques such as silica gel, ODS, and Sephadex LH-20 column chromatography, as well as preparative HPLC, fourteen C21 steroidal compounds were isolated from the chloroform extract of Cynanchum wallichii Wight. The structures of these compounds were identified through spectroscopic techniques including mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), ultraviolet spectroscopy (UV), and infrared spectroscopy (IR) methods as cynanotonin E (1), qingyangshengenin (2), qinyangshengenin-3-O-β-D-cymaropyranoside-(1→4)-β-D-cymaropyranoside (3), qinyangshengenin-3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosy-(1→4)-β-D-digitoxopyranoside (4), qinyangshengenin-3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-digitoxopyranoside (5), 12-O-benzoylsarcostin-3-O-β-D-oleandropyranosy-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranosyl (6), 12-O-benzoylsarcostin-3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-digitoxopyranosyl (7), caudatin-3-O-β-D-digitoxopyranoside (8), caudatin-3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranoside (9), caudatin-3-O-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (10), caudatin-3-O-β-D-cymaropyranosyl-(1→4)-β-D-digitoxopyranoside (11), otophylloside B (12), otophylloside E (13) and otophylloside F (14). Among them, compound 1 is a new compound. The cytotoxic activities of compounds 1-14 against human hepatocellular carcinoma HepG2 cells were tested using the MTS method. The results indicated that all compounds exhibited good inhibitory activities against the proliferation of HepG2 cells, with IC₅₀ values ranging from 4.3 ± 1.25 - 26.3 ± 1.65 μmol·L^-1. Among them, the inhibitory activities of compounds 1, 3 and 6-14 were all stronger than that of the positive control cisplatin (DDP, IC₅₀: 15.9 ± 1.25 μmol·L^-1).

The transdermal delivery system of traditional Chinese medicine (TCM) has emerged as a vital alternative to conventional administration routes, particularly for chronic disease management, owing to its advantages in avoiding hepatic first-pass effects, maintaining stable blood drug concentrations, improving patient compliance, and enabling sustained release. However, the efficiency of TCM transdermal delivery is significantly constrained by the "brick-and-mortar structure" barrier of the stratum corneum and the inherent complexity of TCM components, which also complicates quality control and mechanistic studies. To address these challenges, innovative strategies have been developed in recent years, including microneedles, nanocarriers (liposomes, nanoemulsions, polymeric nanoparticles, nanocrystals and self-assembled nanomicelles), permeation enhancers, iontophoresis, and sonophoresis. Synergistic permeation-enhancing strategies further overcome limitations of single-technique approaches. These technologies demonstrate substantial clinical value in dermatological therapy, pain management, wound healing, and related fields.