Four previously undescribed lanostane tetracyclic triterpenoids baoslingzhines T-W (1-4) were isolated from Ganoderma lucidum. Their structures including relative and absolute configurations were assigned by spectroscopic methods and ECD calculations.

Six compounds including three new compounds were obtained from the fruiting bodies of Ganoderma lucidum in Baoshan area. These structures were identified as baosacid A (1), baosside A (2), ethyl 2,5-dihydroxy-γ-oxobenzenebutanoate (3), australins A (4), 2,5-dihydroxy-γ-oxobenzenebutanoic acid (5), and methyl 2,5-dihydroxy-γ-oxobenzenebut anoate (6) on the basis of spectroscopic methods. In addition, compound 5 is a newly occurring natural product.

Radiation-induced intestinal injury (RIII) is a common syndrome in the radiotherapy of abdominal and pelvic malignant tumors, heavily influencing the living quality, but no specific clinical regimens are available. Inulin is a naturally soluble dietary fiber. Clostridium butyricum (Cb) is a strict Gram-positive anaerobic bacillus, which can secrete and produce a large number of butyric acid, improving the intestinal barrier function and reducing the growth and colonization of opportunistic bacteria. A synbiotic of inulin gels (IG) and Cb exerts the synergistic effect of prebiotic intestinal retention and probiotics. In this study, an oral synbiotic of IG and Cb was applied for the prevention and treatment of RIII and the mechanisms were explored. Animal experiments were approved by the Ethics Committee of the Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations (authorizing number: IACUC-DWZX-2022-525). An RIII mouse model was established after whole abdominal γ-ray radiation of 13 Gy. The synbiotic was intragastrically administered to the mice 1 h pre-radiation. Compared to the models, the mice of the synbiotic group had more regenerated intestinal crypts, longer villus and colon, and more tight junction protein on day 3.5. Moreover, the mice of the synbiotic group had an obvious increase in the relative abundance of gut microbiota on day 7, especially the amounts of multiple probiotics and short-chain fatty acid metabolites. On day 14, the mice of the synbiotic group had highly low permeability of intestinal mucosa according to the fluorescence labeling experiment, which was close to the normal level. Moreover, the mice of the synbiotic group showed a high decrease of proinflammatory factors including tumor necrosis factor-α and interleukin-6, close to the normal levels. Therefore, the oral synbiotic can alleviate the syndromes of RIII and improve the repair of damaged intestinal and colon tissues, and its protective effect is better than IG and Cb. The oral synbiotic is a safe and effective biological drug against RIII.

Dendritic cells (DCs) play a critical role in both innate and adaptive immunity, particularly in regulating antitumor immune responses. However, immunosuppressive cytokines in the tumor microenvironment and lipid peroxidation imbalance within DCs limit their ability to activate tumor-specific T cells effectively. To address this, we developed a novel biomimetic nanodrug delivery platform using artificial intelligence (AI). This platform encapsulates curcumin nanoparticles in bacterial outer membrane vesicles (OMVs) to enhance DCs function through a dual approach: targeted drug delivery and immune activation. In vitro experiments demonstrated that curcumin reduced lipid peroxidation stress in DCs by modulating the IRE1α-XBP1 signaling pathway, thereby restoring their antigen-presenting function. Additionally, OMVs not only acted as efficient drug carriers but also as immune activators, promoting DCs maturation and enhancing tumor-specific immune responses. This study presents a promising strategy for improving antitumor immunotherapy and offers new insights into the application of AI in drug delivery systems.

Combined radiation and burn injury (CRBI) is induced by simultaneous or sequential ionizing radiation damage and skin burns. CRBI weakens the immune ability, leading to drug-resistant bacterial infections and delayed wound healing. Bdellovibrio-and-like organisms (BALO) are naturally predatory bacterium that can prey on most Gram-negative bacteria by entering the periplasmic space of their prey and degrading the biomolecules of host cells. In this study, we combined gelatin, calcium alginate, and activated BALO water samples to form bio-inks to three-dimensional (3D)-print BALO-loaded hydrogels (TDBG) for the treatment of CRBI combined with multidrug-resistant Acinetobacter baumannii (MRAB) infection. The freeze-dried 3D-printed hydrogel exhibited a 3D network structure attached with gelatin films, and owned good printability and biocompatibility. The printability improved adaptation to wound shapes for the personalized treatment of infected wounds. The 3D network structure allowed the surviving and motion of BALO, favoring its high predatory activity. All animal experiments were approved by the Ethics Committee of Academy of Military Medical Sciences, and the experiments were conducted in accordance with relevant guidelines and regulations (approval number: IACUC-DWZX-2022-834). TDBG treatment improved wound healing by accelerating the mouse wound closure rate of CRBI combined with MRAB infection, reducing the expression of pro-inflammatory cytokines in the wound tissues, and increasing collagen deposition. This study expands the application scope of live biological products and provides a basis for their development and clinical applications.

L-Asparaginase (ASNase), an aminohydrolase, is widely utilized in the pharmaceutical and food industries. Among its various sources, Escherichia coli K12-derived EcASNase has been employed as a clinical drug for the treatment of acute lymphoblastic leukemia (ALL). However, the limited catalytic activity and stability of EcASNase have restricted its broader application in medicine and food processing. In this study, a random mutagenesis library was constructed via error-prone PCR, followed by high-throughput screening using a coupled bacterial growth strategy. Three positive mutants with enhanced activity were identified: G38S, Q212Y, and S274P, exhibiting activities 1.4-, 1.1-, and 1.2-fold higher than the wild type (WT), respectively. Saturation mutagenesis libraries were subsequently generated for positions 38, 212, and 274, leading to the identification of mutants G38A, G38S, G38Q and G38V, with k_cat/K_m values 1.7-, 1.5-, 2.1-, and 2.2-fold higher than WT, respectively. Among these, G38V emerged as the most active mutant, with a T_m value increased by 8.4 ℃ compared to WT. Combination mutations, such as G38V/Q212F and G38V/S274P, failed to yield further activity improvements. This research elucidates the contributions of critical residues to the enzyme's activity and stability, providing novel insights into the rational design and development of therapeutic enzymes.

Oral probiotics are susceptible to the gastrointestinal environment, so the number of probiotics reaching the intestine is small and difficult to colonize, limiting the application of probiotic therapy. In this study, Lactobacillus rhamnosus (LGG), a common probiotic, was chosen as a model, and layer-by-layer encapsulated LGG-loaded porous microspheres with glycol chitosan (GCS) and sodium alginate (SA) were prepared to investigate it's in vitro properties. Poly-L-lactic acid porous microspheres (PLPM) were prepared by the complex milk-solvent evaporation method, with rounded morphology, uniform size, open and connected porous structure, and the average particle size of 138.5 μm. The PLPM were co-incubated with LGG for 8 h at 37 ℃ to obtain the LGG-loaded porous microspheres (LPM) with high bacterial loadings. The surface of the LPM were wrapped with GCS and SA layer by layer by electrostatic action to obtain the layer-by-layer encapsulated LGG-loaded porous microspheres with GCS and SA (AGLPM). In vitro experiments demonstrated that AGLPM could tolerate simulated gastric fluid at pH 1.2 and simulated intestinal fluid at pH 7.4 for 2 h, and its stability was significantly better than that of bare LGG. AGLPM was a better probiotic dosage form.

With the increasing abuse of antibiotics and the growing resistance of bacteria, it is urgent to find new antibacterial agents. Numerous constituents of traditional Chinese medicine exhibit pronounced antibacterial, anti-inflammatory, and antioxidant pharmacological properties, often operating through multiple mechanisms, thereby positioning them as a vital source for the development of novel antibacterial agents in the future. Nevertheless, the antibacterial constituents of traditional Chinese medicine exhibit challenges such as inadequate stability, low solubility, and suboptimal intelligent release capabilities, which hinder their extensive application in antibacterial formulations. Metal-organic framework materials serve as highly effective drug carriers for antibacterial constituents of traditional Chinese medicine, attributed to their high specific surface area, elevated porosity, controllable pore dimensions, and responsive release properties. Furthermore, they not only enhance the stability and solubility of these antibacterial constituents while also exhibiting inherent antibacterial activity and responsive release capabilities. This paper presents a comprehensive overview of bacterial resistance mechanisms and the action pathways of antibacterial constituents of traditional Chinese medicine against resistant bacteria. Additionally, it highlights the current advancements in metal-organic framework materials and their application in the delivery systems for these antibacterial constituents, aiming to provide valuable insights for the research and innovation of formulations based on traditional Chinese medicine.

Bacterial infectious diseases persistently pose severe threats to human health, development of livestock and aquaculture industries, and ecological stability. The extensive use of conventional antibiotics has led to increasingly critical issues of bacterial resistance, making the development of novel and effective strategies for preventing and treating bacterial infections an urgent priority. Bdellovibrio bacteriovorus, as a genus of parasitic bacteria that prey on other bacteria, exhibits lytic activity against various pathogenic species and demonstrates potential for combating bacterial infections. However, the direct application of B. bacteriovorus suspensions or powders faces challenges including rapid clearance, susceptibility to immune system elimination, difficulty in maintaining their vitality, and poor user compliance. Recent advancements in engineered B. bacteriovorus technology have created new opportunities for more precise and efficient utilization of these predators in infection control. This paper reviews recent advances in engineered B. bacteriovorus for bacterial infection control, with particular emphasis on engineering strategies based on formulation design, surface modification, and genetic editing, along with their therapeutic applications. The review aims to provide valuable insights for advancing research on engineered B. bacteriovorus technologies.

Lymphocyte activation gene 3 (LAG-3) is an important inhibitory receptor on T cells, which plays a crucial role in tumor immune evasion. LAG-3 is primarily expressed on activated T cells, natural killer (NK) cells and B cells, et al. By binding to its ligands, LAG-3 inhibits T cell proliferation, activation, and effector functions. LAG-3 has emerged as the third immune checkpoint protein (ICP) used in clinical practice, following programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Currently, there has been at least 20 LAG-3-targeted drugs undergoing clinical trials. This article mainly reviews the structure, expression regulation, ligands, co-expressed ICP of LAG-3, as well as its application in tumor immunotherapy, and discusses the current challenges of targeting LAG-3 research.