Hericium rajendrae is an emerging species in the genus Hericium with few members. Despite being highly regarded due to its rarity, knowledge about H. rajendrae remains limited. In this study, we sequenced, de novo assembled, and annotated the complete genome of H. rajendrae NPCB A08, isolated from the Qinling Mountains in Shaanxi, China, using the Illumina NovaSeq and Nanopore PromethION technologies. Comparative genomic analysis revealed similarities and differences among the genomes of H. rajendrae, H. erinaceus, and H. coralloides. Phylogenomic analysis revealed the divergence time of the Hericium genus, while transposon analysis revealed evolutionary characteristics of the genus. Gene family variation reflected the expansion and contraction of orthologous genes among Hericium species. Based on genomic bioinformation, we identified the candidate genes associated with the mating system, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Furthermore, metabolite profiling and comparative gene clusters analysis provided strong evidence for the biosynthetic pathway of erinacines in H. rajendrae. This work provides the genome of H. rajendrae for the first time, and enriches the genomic content of the genus Hericium. These findings also facilitate the application of H. rajendrae in complementary drug research and functional food manufacturing, advancing the field of pharmaceutical and functional food production involving H. rajendrae.

The culinary medicinal mushroom Hericium erinaceus holds significant global esteem and has garnered heightened interest within increasingly ageing societies due to its pronounced neuroprotective and anti-neuroinflammatory properties. Within this study, two novel diterpenes, 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2); three known xylosyl cyathane diterpenoids, Erinacine A (3), Erinacine C (4), and Erinacine F (5); and four lanostane-type triterpenoids, and three cyclic dipeptides (10–12), in addition to orcinol (13), were isolated from the rice-based cultivation medium of H. erinaceus. Their structures were determined by NMR, HR-ESI-MS, ECD, and calculated NMR. Compound 1 marks a pioneering discovery as the first verrucosane diterpene originating from basidiomycetes, amplifying the scope of fungal natural product chemistry, and the intricate stereochemistry of Compound 5 has been comprehensively assessed for the first time. Compounds 2–5 not only showed encouraging neurotrophic activity in rat adrenal pheochromocytoma PC-12 cells, but also significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia cell cultures with IC₅₀ values as low as 5.82 ± 0.18 μM. To elucidate the mechanistic underpinnings of these bioactivities, molecular docking simulation was used to analyze and support the interaction of 1 and 2 with inducible NO synthase (iNOS), respectively. In particular, compound 2, a cyathane-xyloside containing an unconventional hemiacetal moiety, is a compelling candidate for the prevention of neurodegenerative diseases. In summation, this investigation contributes substantively to the panorama of fungal diterpene structural diversity, concurrently furnishing additional empirical substantiation for the role of cyathane diterpenes in the amelioration of neurodegenerative afflictions.

Bacterial-infected skin wounds, especially those caused by drug-resistant pathogens accompanied by persistent inflammation, remain a major clinical therapeutic challenge. Rising antimicrobial resistance compromises the therapeutic effect of conventional single-agent antibiotics, creating an urgent demand for novel wound therapeutics that integrate bactericidal potency, immunomodulation and tissue regeneration capacity. In this work, an injectable multifunctional chitosan-based hydrogel (C@MC) was developed, which simultaneously incorporates metformin hydrochloride (as a potential antibiotic adjuvant) and cefazolin sodium (as a β-lactam class antibacterial drug). The optimized C@MC possesses interconnected three-dimensional pores with an initial storage modulus of ~0.83 kPa (C@MC₃₆₀), featuring desirable mechanical strength, injectability, tissue adhesion and dual pH/glucose-responsive sustained drug release. In vitro evaluations revealed the dose-dependent bactericidal activity of C@MC against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and New Delhi metallo-β-lactamase-1-producing E. coli (NDM-1 E. coli, resistant bacteria). The highest drug-laden group nearly eliminated all wound bacteria in vitro. It scavenged reactive oxygen species (ROS) to lower cellular MDA levels and suppress pro-inflammatory TNF-α and IL-6 in LPS-stimulated RAW 264.7 macrophages. In full-thickness mouse wounds infected with NDM-1 E. coli, C@MC₃₆₀ achieved nearly complete wound closure, with only a 4.2% residual wound area on day 14, accompanied by suppressed inflammatory infiltration and accelerated wound regeneration. This dual-drug hydrogel integrates antibiotic potentiation, anti-inflammation and antioxidation, providing an intervention regimen for skin wounds infected with drug-resistant bacteria.