Hongwu Wang

Liver X receptors (LXRs), comprising LXRα and LXRβ, are oxysterol-responsive nuclear receptors that regulate cholesterol homeostasis and inflammatory signaling. In the central nervous system (CNS), LXR activity influences amyloid-β metabolism, glial responses, synaptic integrity, myelination, and blood–brain barrier function. This narrative review synthesizes shared and disease-specific mechanisms across neurodegenerative and demyelinating disorders, distinguishing established experimental effects from proposed pathways. We compare representative LXR modulators by receptor and transcriptional selectivity, CNS exposure, efficacy, and safety. Particular attention is given to hepatic lipogenesis caused by systemic LXRα activation and to LXRβ-selective or function-selective ligands, brain-targeted delivery, combination strategies, and biomarker-guided patient stratification. Although preclinical findings support therapeutic potential, clinical efficacy remains unproven. Priorities include cell-type-specific causal validation, quantitative CNS target engagement, and long-term safety assessment.

Icaritin (ICT), a biologically active isoprenylated flavonoid, which has been shown to delay liver fibrosis, inhibit cancer cell proliferation and other therapeutic effects in the treatment of hepatocellular carcinoma. However, traditional methods for icaritin preparation suffer from significant drawbacks such as high environmental pollution, energy consumption, and low yield. In this study, snailase (SNA) was immobilized for the first time in hollow silica nanospheres (HSN) through facile and novel in situ immobilization and soft template removal method to construct highly active biocatalysts (SNA@HSN) where enzymes in the cavity exhibit “immobilized but not rigid state”. The resultant SNA@HSN showed excellent activity (78% activity recovery) and stability suffered from extreme pH, temperature, and organic solvents. Meanwhile, the reusability and storage stability of SNA@HSN were satisfactory. After 5 cycles, SNA@HSN still maintained 79% original activity. Especially, SNA@HSN exhibited highly efficient biotransformation of icariin (ICA) to ICT in deep eutectic solvents (DESs) system. ICT yield in choline chloride–propylene glycol (ChCl:P, 25% v/v) system was 111% higher than that of aqueous system, reached 374 mg/L. Thus, this study developed an efficient methodology for icaritin preparation through the integration of enzymatic catalysis and environmentally friendly catalytic medium.

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and ginger contains phenolic constituents with anti-inflammatory potential. This study evaluated the antiarthritic efficacy of ginger ethanolic extract (GE) and explored its potential mechanisms through integrated pharmacological and computational approaches. Methods: GE was prepared by 70% ethanol reflux extraction and administered to adjuvant-induced arthritis (AIA) rats, with methotrexate as a positive control. Body weight; paw swelling; arthritis index; spleen index; and serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured. Chemical profiling was performed by ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), followed by network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Results: GE attenuated paw edema, arthritis index elevation, splenic enlargement, and elevated serum inflammatory mediators in AIA rats. UPLC-Q-TOF-MS/MS annotated 38 constituents, mainly gingerols, shogaols, gingerdiones, gingerdiols, and related phenolic derivatives. Network analysis identified 217 overlapping ginger- and RA-associated targets, with TNF, IL6, and matrix metalloproteinase 9 (MMP9) prioritized among inflammatory and matrix-remodeling nodes. Docking and MD simulations supported stable predicted interactions for 8-gingerol-TNF and 6-gingerol-MMP9. Conclusions: GE showed antiarthritic activity in AIA rats. The integrated chemical, in vivo, and computational data suggest that ginger phenolics may modulate inflammatory mediators and candidate RA-related pathways; however, these mechanisms remain exploratory and require histological, tissue-level, and molecular validation.

Extended-spectrum β-lactamase genes in foodborne Salmonella enterica can disseminate through mobile multidrug-resistance platforms. IncHI2 plasmids are important resistance vehicles capable of carrying complex resistance regions and facilitating their horizontal transfer across diverse bacterial backgrounds, but the transfer and genomic organization of IncHI2 elements co-carrying bla_LAP-2 and bla_CTX-M-55 remain insufficiently characterized. This study investigated two multidrug-resistant foodborne isolates recovered in Shanghai in 2022: Salmonella Agona ST13 isolate Sal22C150 and Salmonella Havana ST1527 isolate Sal22P208. Antimicrobial susceptibility testing, whole-genome sequencing, conjugation, plasmid-retention analysis, comparative genomics, as well as strain- and plasmid-level phylogenetic analyses were performed. Both isolates exhibited broad antimicrobial resistance, including resistance to extended-spectrum cephalosporins. In both isolates, bla_LAP-2 and bla_CTX-M-55 co-transferred with the IncHI2 replicon to Escherichia coli J53 at frequencies of (4.95 ± 0.41) × 10⁻⁵ and (4.46 ± 0.42) × 10⁻⁶ transconjugants per donor cell, respectively. All tested plasmid markers remained detectable through 20 passages without antimicrobial selection. Complete assembly of Sal22P208 confirmed the location of the three β-lactamase genes on the 275,096 bp IncHI2 plasmid pSal22P208. The plasmid contained a conserved conjugative backbone and mosaic accessory regions carrying 15 antimicrobial-resistance determinants together with mercury- and tellurium-resistance loci. SNP-based analysis placed pSal22P208 within a closely related cluster containing six reference IncHI2 plasmids differing by fewer than 30 SNPs and recovered from Salmonella and E. coli of animal, food, and human origin, suggesting a broad distribution of this plasmid lineage across diverse bacterial and ecological backgrounds. Sal22P208 additionally contained a Tn3-associated chromosomal multidrug-resistance region between rpmJ and rpmE that shared extensive structural similarity with a region in Citrobacter braakii LBA3. These findings highlight the role of transferable IncHI2 resistance platforms in the horizontal dissemination and short-term post-transfer maintenance of linked resistance determinants, while chromosomally integrated resistance regions may provide an additional route for the accumulation and inheritance of multidrug resistance in foodborne Salmonella.

Multi-enzyme immobilization offers promise for sensitive glucose detection, but traditional random co-immobilization hampers spatial control. Here, a compartmentalized system (HRP.PDA.GOx@NPC-10) was constructed by localizing GOx and HRP in the inner and outer polydopamine layers on hierarchical porous carbon spheres. This method can precisely control the spatial arrangement of enzyme molecules, effectively reduce the inhibitory effects of H₂O₂, and enhance the catalytic efficiency of multi-enzyme catalysis. The immobilization yields of GOx and HRP reached 54.6% and 65.0%, respectively. The resultant HRP.PDA.GOx@NPC-10 exhibited 1.65-folds higher activity than free enzymes and maintained favorable stability under extreme pH and temperature conditions. After 7 cycles, HRP.PDA.GOx@NPC-10 retained 75.66% of its initial activity, demonstrating reusability. Especially, HRP.PDA.GOx@NPC-10 has been demonstrated to possess a glucose detection limit as low as 0.28 μM and a reaction time of only 3 min, indicating its potential for practical glucose detection.

As a versatile biocatalyst in the lyase family, phenylalanine ammonia lyase (PAL, EC 4.3.1.24) appears naturally in diverse organisms including higher plants, numerous fungi, yeasts, Streptomyces species, and some Cyanobacteria. Naturally, catalyzed by PAL, l-phenylalanine (l-Phe) undergoes stereospecific deamination, yielding trans-cinnamic acid (t-CA) and ammonia. PAL has made major strides in a number of clinical, industrial, and biotechnological applications over last few decades. Since its initial characterization in Hordeum vulgare, PAL's involvement in the phenylpropanoid pathway has been the subject of extensive investigation both in plants and in microorganism. However, there are few articles focusing on the overall summary of microbial PAL. This mini-review systematically examines current breakthroughs in microbial PAL technology, encompassing both production optimization strategies and novel application frontiers. By summarizing cutting-edge research and industrial practices, this work aims to catalyze the next wave of PAL-based innovations, positioning microbial PAL as a transformative force in 21st-century biotechnology.