Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM: To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS: In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS: First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION: The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

LC/MS-guided isolation and GNPS procedures to identify flavonoid of HCoV-OC43 inhibitors.

The screening of based target compounds supported by LC/MS, MS/MS and Global Natural Products Social (GNPS) used to identify the compounds 1-10 of Butea monsperma. They were evaluated in human malignant embryonic rhabdomyoma cells (RD cells) infected with Human coronavirus OC43 (HCoV-OC43) and showed significant inhibitory activity. Target inhibition tests showed that compounds 6 and 8 inhibited the proteolytic enzyme 3CLpro, which is widely present in coronavirus and plays an important role in the replication process, with an effective IC50 value. The study confirmed that dioxymethylene of compound 8 may be a key active fragment in inhibiting coronavirus (EC50 7.2 µM, SI > 139.1). The results have led to identifying natural bioactive compounds for possible inhibiting HCoV-OC43 and developing drug for Traditional Chinese Medicine (TCM).

Clinical significance and biological function of interferon regulatory factor 1 in non-small cell lung cancer.

The clinical application and biological function of interferon regulatory factor 1 (IRF1) in non-small cell lung cancer (NSCLC) patients undergoing chemoimmunotherapy remain elusive. The aim of this study was to investigate the predictive and prognostic significance of IRF1 in NSCLC patients. We employed the cBioPortal database to predict frequency changes in IRF1 and explore its target genes. Bioinformatic methods were utilized to analyze the relationship between IRF1 and immune regulatory factors. Retrospective analysis of clinical samples was conducted to assess the predictive and prognostic value of IRF1 in chemoimmunotherapy. Additionally, A549 cells with varying IRF1 expression levels were constructed to investigate its effects on NSCLC cells, while animal experiments were performed to study the role of IRF1 in vivo. Our findings revealed that the primary mutation of IRF1 is deep deletion and it exhibits a close association with immune regulatory factors. KRAS and TP53 are among the target genes of IRF1, with interferon and IL-2 being the predominantly affected pathways. Clinically, IRF1 levels significantly correlate with the efficacy of chemoimmunotherapy. Patients with high IRF1 levels exhibited a median progression-free survival (mPFS) of 9.5 months, whereas those with low IRF1 levels had a shorter mPFS of 5.8 months. IRF1 levels positively correlate with PD-L1 distribution and circulating IL-2 levels. IL-2 enhances the biological function of IRF1 and recapitulates its role in vivo in the knockdown group. Therefore, IRF1 may possess predictive and prognostic value for chemoimmunotherapy in NSCLC patients through the regulation of the IL-2 inflammatory pathway.

Whole-genome sequencing of a worldwide collection of sugarcane cultivars (Saccharum spp.) reveals the genetic basis of cultivar improvement.

Sugarcane is the main source of sugar worldwide, and 80% of the sucrose production comes from sugarcane. However, the genetic differentiation and basis of agronomic traits remain obscure. Here, we sequenced the whole-genome of 219 elite worldwide sugarcane cultivar accessions. A total of approximately 6 million high-quality genome-wide single nucleotide polymorphisms (SNPs) were detected. A genome-wide association study identified a total of 2198 SNPs that were significantly associated with sucrose content, stalk number, plant height, stalk diameter, cane yield, and sugar yield. We observed homozygous tendency of favor alleles of these loci, and over 80% of cultivar accessions carried the favor alleles of the SNPs or haplotypes associated with sucrose content. Gene introgression analysis showed that the number of chromosome segments from Saccharum spontaneum decreased with the breeding time of cultivars, while those from S. officinarum increased in recent cultivars. A series of selection signatures were identified in sugarcane improvement procession, of which 104 were simultaneously associated with agronomic traits and 45 of them were mainly associated with sucrose content. We further proposed that as per sugarcane transgenic experiments, ShN/AINV3.1 plays a positive role in increasing stalk number, plant height, and stalk diameter. These findings provide comprehensive resources for understanding the genetic basis of agronomic traits and will be beneficial to germplasm innovation, screening molecular markers, and future sugarcane cultivar improvement.

Primate Model Carrying LMNA Mutation Develops Dilated Cardiomyopathy.

To solve the clinical transformation dilemma of lamin A/C (LMNA)-mutated dilated cardiomyopathy (LMD), we developed an LMNA-mutated primate model based on the similarity between the phenotype of primates and humans. We screened out patients with LMD and compared the clinical data of LMD with TTN-mutated and mutation-free dilated cardiomyopathy to obtain the unique phenotype. After establishment of the LMNA c.357-2A>G primate model, primates were continuously observed for 48 months, and echocardiographic, electrophysiological, histologic, and transcriptional data were recorded. The LMD primate model was found to highly simulate the phenotype of clinical LMD. In addition, the LMD primate model shared a similar natural history with humans.

Diarylheptanoids with neuroprotective effects from Alpinia officinarum rhizomes.

Forty-three diarylheptanoids were isolated from Alpinia officinarum rhizomes among them eight ones (1-6) were undescribed compounds whose structures were identified by UV, IR, HRESIMS, and NMR. The neuroprotective effects of these diarylheptanoids were evaluated on H2O2-damaged SH-SY5Y cells. Compounds 7, 10, 12, 20, 22, 25, 28, 33, 35, 37, and 42 presented significant neuroprotective effects than that of the positive control (EGCG) at the concentrations of 5, 10 or 20 µM. Compounds 10, 22, 25, and 33 significantly reduced the ROS levels and inhibited the generations of MDA and NO in oxidative injured cells to display neuroprotective effects. This study lay the foundation for the application of Alpinia officinarum rhizomes.

Abietane diterpenoids with anti-neuroinflammation activity from Rosmarinus officinalis.

A total of 12 abietane diterpenoids were isolated and identified from Rosmarinus officinalis in which 6 ones were undescribed compounds. Their structures were illuminated by the HRESIMS, NMR, and ECD methods and named as rosmarinusin Q-V (1-6). It worthy mentioned that rosmarinusin Q was a novel abietane diterpenoid with 6/6/5 skeleton whose C ring was an α,ß-unsaturated five-element ketone. All the compounds and four compounds (13-16) reported in our previous paper were evaluated their anti-neuroinflammatory activities on the LPS-induced BV2 cells. Compounds 5, 8, 9, 11, and 15 displayed significant anti-neuroinflammatory activity at the concentration of 10, 20, and 40 µM respectively. These results confirmed that R. officinalis contained abundant abietane diterpenoids and these compounds showed potential values of anti-neuroinflammation which could be developed as neuroprotective agents for the treatment of nerve damage caused by inflammation.

The Role of Calcium and Iron Homeostasis in Parkinson's Disease.

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson's disease) is the second most common neurological disorder in humans, for which there are currently no viable treatment options or effective strategies to cure and delay progression. Pathological hallmarks of PD, such as dopaminergic neuronal death and intracellular α-synuclein deposition, are closely involved in perturbations of iron and calcium homeostasis and accumulation. Here, we summarize the mechanisms by which Ca2+ signaling influences or promotes PD progression and the main mechanisms involved in ferroptosis in Parkinson's disease. Understanding the mechanisms by which calcium and iron imbalances contribute to the progression of this disease is critical to developing effective treatments to combat this devastating neurological disorder.

Genome Mining of Cinnamoyl-Containing Nonribosomal Peptide Gene Clusters Directs the Production of Malacinnamycin.

Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of actinobacterial secondary metabolites that display a broad spectrum of biological activities. Here, we present a genome mining approach targeting cyclase and is isomerase to discover new CCNPs, which led to the identification of 207 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named malacinnamycin was identified. A plausible biosynthetic pathway for malacinnamycin was deduced by bioinformatics analysis.

Polymorphism in the Ruddlesden-Popper Nickelate La3Ni2O7: Discovery of a Hidden Phase with Distinctive Layer Stacking.

We report the discovery of a novel form of Ruddlesden-Popper (RP) nickelate that stands as the first example of long-range, coherent polymorphism in this class of inorganic solids. Rather than the well-known, uniform stacking of perovskite blocks ubiquitously found in RP phases, this newly discovered polymorph of the bilayer RP phase La3Ni2O7 adopts a novel stacking sequence in which single-layer and trilayer blocks of NiO6 octahedra alternate in a "1313" sequence. Crystals of this new polymorph are described in space group Cmmm, although we note evidence for a competing Imam variant. Transport measurements at ambient pressure reveal metallic character with evidence of a charge density wave transition with an onset at T ≈ 134 K. The discovery of such polymorphism could reverberate to the expansive range of science and applications that rely on RP materials, particularly the recently reported signatures of superconductivity in bilayer La3Ni2O7 with Tc as high as 80 K above 14 GPa.

Supra-Blan2 t score as a multisystem-based risk score to predict poor 3-month outcome in acute ischemic stroke patients with intravenous thrombolysis.

AIM: To develop and validate a novel weighted score integrating multisystem laboratory and clinical variables to predict poor 3-month outcome (mRS score of 3-6) in acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT) therapy. METHODS: We retrospectively analyzed data from Trial of Revascularization Treatment for Acute Ischemic Stroke study. The Supra-Blan2 t score was derived using the data on age, the National Institutes of Health Stroke Scale score, history of atrial fibrillation, blood sugar level, neutrophil count, direct bilirubin level, platelet-lymphocyte ratio, and TnI level in the derivation cohort of 433 patients, and validated in a cohort of 525 patients. Furthermore, we compared the performance of the Supra-Blan2 t score with DRAGON, TURN, and SPAN-100 scores. RESULTS: The discrimination capacity in the derivation and validation cohorts was good for poor 3-month outcome (the area under the curve was 0.821 and 0.843, respectively). The cumulative incidence of poor 3-month outcome significantly increased across risk categories in the derivation (low-risk, 9.2%; medium-risk, 17.4%; and high-risk, 58.8%) and validation cohorts (12.7%, 36.5%, and 73.6%, respectively). The performance of the Supra-Blan2 t score was similar to or superior to DRAGON, TURN, and SPAN-100 scores. CONCLUSION: The Supra-Blan2 t score, based on easily available multisystem laboratory and clinical variables, reliably predicted poor 3-month functional outcome in AIS patients treated with IVT therapy featuring good calibration and discrimination.

Long-term in vivo chimeric cells tracking in non-human primate.

Non-human primates (NHPs) are increasingly used in preclinical trials to test the safety and efficacy of biotechnology therapies. Nonetheless, given the ethical issues and costs associated with this model, it would be highly advantageous to use NHP cellular models in clinical studies. However, developing and maintaining the naïve state of primate pluripotent stem cells (PSCs) remains difficult as does in vivo detection of PSCs, thus limiting biotechnology application in the cynomolgus monkey. Here, we report a chemically defined, xeno-free culture system for culturing and deriving monkey PSCs in vitro. The cells display global gene expression and genome-wide hypomethylation patterns distinct from monkey-primed cells. We also found expression of signaling pathways components that may increase the potential for chimera formation. Crucially for biomedical applications, we were also able to integrate bioluminescent reporter genes into monkey PSCs and track them in chimeric embryos in vivo and in vitro. The engineered cells retained embryonic and extra-embryonic developmental potential. Meanwhile, we generated a chimeric monkey carrying bioluminescent cells, which were able to track chimeric cells for more than 2 years in living animals. Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models for clinical studies.

Molecular comparison of organic matter removal from shale gas flowback wastewater: Ozonation versus Fenton process.

Shale gas extraction process generates a large amount of shale gas flowback wastewater (SGFW) containing refractory organic compounds, which can pose serious environmental threats if not properly treated. However, the extremely complex compositions of organics in SGFW are still unknown and their transformation pathways in O3- and •OH-dominated systems are not well recognized, which restrain the selection of treatment technology and optimization of operational parameters. The removal characteristics and reaction mechanism of dissolved organic matter (DOM) in SGFW treated by ozonation and Fenton processes were comparatively investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The results showed that both processes could degrade low-oxygen highly unsaturated and phenolic organics, polyphenolics and polycyclic aromatics, and transform them into aliphatic organics and high-oxygen highly unsaturated and phenolic organics. With increasing action of reactive oxygen species (O3 for ozonation and •OH for Fenton process), the degradation products (mainly aliphatic organics) increased during ozonation. However, in Fenton process, a wider range of DOM was removed without aliphatic organics accumulation. The degradation mechanisms of DOM during ozonation and Fenton processes included oxygen addition reactions (+3O, +H2O2, and +2O) as dominant pathways. However, ozonation showed more violent oxygenation, hydroxylation, and carboxylation, while Fenton process presented more violent chain-breaking reactions. These results revealed the selective oxidation of ozone and nonselective oxidation of •OH during SGFW treatment, and provided theoretical support for selecting SGFW treatment approaches.

C9orf72 poly(PR) aggregation in nucleus induces ALS/FTD-related neurodegeneration in cynomolgus monkeys.

Poly(PR) is a dipeptide repeat protein comprising proline and arginine residues. It is one of the translational product of expanded G4C2 repeats in the C9orf72 gene, and its accumulation is contributing to the neuropathogenesis of C9orf72-associated amyotrophic lateral sclerosis and/or frontotemporal dementia (C9-ALS/FTD). In this study, we demonstrate that poly(PR) protein alone is sufficient to induce neurodegeneration related to ALS/FTD in cynomolgus monkeys. By delivering poly(PR) via AAV, we observed that the PR proteins were located within the nucleus of infected cells. The expression of (PR)50 protein, consisting of 50 PR repeats, led to increased loss of cortical neurons, cytoplasmic lipofuscin, and gliosis in the brain, as well as demyelination and loss of ChAT positive neurons in the spinal cord of monkeys. While, these pathologies were not observed in monkeys expressing (PR)5, a protein comprising only 5 PR repeats. Furthermore, the (PR)50-expressing monkeys exhibited progressive motor deficits, cognitive impairment, muscle atrophy, and abnormal electromyography (EMG) potentials, which closely resemble clinical symptoms seen in C9-ALS/FTD patients. By longitudinally tracking these monkeys, we found that changes in cystatin C and chitinase-1 (CHIT1) levels in the cerebrospinal fluid (CSF) corresponded to the phenotypic progression of (PR)50-induced disease. Proteomic analysis revealed that the major clusters of dysregulated proteins were nuclear-localized, and downregulation of the MECP2 protein was implicated in the toxic process of poly(PR). This research indicates that poly(PR) expression alone induces neurodegeneration and core phenotypes associated with C9-ALS/FTD in monkeys, which may provide insights into the mechanisms of disease pathogenesis.

Fenton oxidation system for treating petroleum-contaminated solid waste: Advances and prospects.

Both normal activities and accidental spills in the petroleum industry generate solid waste that contain petroleum-contaminated pollutants (referred to as "petroleum-contaminated solid waste"), which mainly include petroleum-contaminated soil, petroleum sludge, and petroleum-based drill cuttings. At present, most relevant studies focus solely on the treatment effects of the Fenton system alone in treating a specific type of petroleum-contaminated solid waste, and systematic studies on the influencing factors, degradation pathways, and applicability of the system are lacking. For this reason, this paper reviews the application and development of the Fenton system to treat petroleum-contaminated solid waste in the period from 2010 to 2021 and summarizes its basic properties. It also compares the influencing factors (e.g., Fenton reagent dosage, initial pH, and catalyst properties), degradation mechanisms, and reagent costs of conventional Fenton, heterogeneous Fenton, chelate-modified Fenton, and electro-Fenton systems for the treatment of petroleum-contaminated solid waste. In addition, the main degradation pathways and intermediate toxicities of typical petroleum hydrocarbons in Fenton systems are analyzed and evaluated, and development directions for the further application of Fenton systems in treating petroleum-contaminated solid waste are proposed.

Sesquiterpenoids from the fruits of Alpinia oxyphylla Miq. and their neuroprotective effect.

The purpose of this study was to identify sesquiterpenoids from Alpinia oxyphylla Miq. fruits under the guidance of LC-MS, and to evaluate their neuroprotective effects on the H2O2-induced SH-SY5Y cells. A total of 35 sesquiterpenoids, including 10 previously unreported ones, were isolated from A. oxyphylla fruits. The neuroprotective effect studies showed that compounds 2, 3, 12, 13, 20, 22, 25, 26, and 35 can improve the viability rates of the H2O2-induced SH-SY5Y cells whose viability rates were ≥ 80% and were higher than that of the positive control. Furthermore, thorough activity studies showed that compounds 3, 13, 22, and 35 can inhibit the production of ROS (reactive oxygen species), and that compounds 13, 22, and 35 can reduce both MDA (Malondialdehyde) and NO levels in the damaged cells in displaying a neuroprotective effect. This study confirmed that the fruits of A. oxyphylla contained abundant sesquiterpenoids with potential neuroprotective effect.

Characterization and expression profiles of the B-box gene family during plant growth and under low-nitrogen stress in Saccharum.

BACKGROUND: B-box (BBX) zinc-finger transcription factors play crucial roles in plant growth, development, and abiotic stress responses. Nevertheless, little information is available on sugarcane (Saccharum spp.) BBX genes and their expression profiles. RESULTS: In the present study, we characterized 25 SsBBX genes in the Saccharum spontaneum genome database. The phylogenetic relationships, gene structures, and expression patterns of these genes during plant growth and under low-nitrogen conditions were systematically analyzed. The SsBBXs were divided into five groups based on phylogenetic analysis. The evolutionary analysis further revealed that whole-genome duplications or segmental duplications were the main driving force for the expansion of the SsBBX gene family. The expression data suggested that many BBX genes (e.g., SsBBX1 and SsBBX13) may be helpful in both plant growth and low-nitrogen stress tolerance. CONCLUSIONS: The results of this study offer new evolutionary insight into the BBX family members in how sugarcane grows and responds to stress, which will facilitate their utilization in cultivated sugarcane breeding.

Electronic structure and correlations in planar trilayer nickelate Pr4Ni3O8.

The discovery of superconductivity in planar nickelates raises the question of how the electronic structure and correlations of Ni1+ compounds compare to those of the Cu2+ cuprate superconductors. Here, we present an angle-resolved photoemission spectroscopy (ARPES) study of the trilayer nickelate Pr4Ni3O8, revealing a Fermi surface resembling that of the hole-doped cuprates but with critical differences. Specifically, the main portions of the Fermi surface are extremely similar to that of the bilayer cuprates, with an additional piece that can accommodate additional hole doping. We find that the electronic correlations are about twice as strong in the nickelates and are almost k-independent, indicating that they originate from a local effect, likely the Mott interaction, whereas cuprate interactions are somewhat less local. Nevertheless, the nickelates still demonstrate the strange-metal behavior in the electron scattering rates. Understanding the similarities and differences between these two families of strongly correlated superconductors is an important challenge.

Sr(Ag1-x Lix )2 Se2 and [Sr3 Se2 ][(Ag1-x Lix )2 Se2 ] Tunable Direct Band Gap Semiconductors.

Synthesizing solids in molten fluxes enables the rapid diffusion of soluble species at temperatures lower than in solid-state reactions, leading to crystal formation of kinetically stable compounds. In this study, we demonstrate the effectiveness of mixed hydroxide and halide fluxes in synthesizing complex Sr/Ag/Se in mixed LiOH/LiCl. We have accessed a series of two-dimensional Sr(Ag1-x Lix )2 Se2 layered phases. With increased LiOH/LiCl ratio or reaction temperature, Li partially substituted Ag to form solid solutions of Sr(Ag1-x Lix )2 Se2 with x up to 0.45. In addition, a new type of intergrowth compound [Sr3 Se2 ][(Ag1-x Lix )2 Se2 ] was synthesized upon further reaction of Sr(Ag1-x Lix )2 Se2 with SrSe. Both Sr(Ag1-x Lix )2 Se2 and [Sr3 Se2 ][(Ag1-x Lix )2 Se2 ] exhibit a direct band gap, which increases with increasing Li substitution (x). Therefore, the band gap of Sr(Ag1-x Lix )2 Se2 can be precisely tuned via fine-tuning x that is controlled by only the flux ratio and temperature.

Antihyperlipidemic effect of Vaccinium dunalianum buds based on biological activity screening and LC-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: The buds of Vaccinium dunalianum Wight are used as folk medicine in the Yi settlement of the Yunnan Province, China. It has long been used as herbal tea in the local area owing to its effects of lowering blood lipids and body weight. However, there are only a few studies on its antihyperlipidemic effects, effective substances and mechanisms, especially its effectiveness in diet-induced hyperlipidemia. AIM OF THE STUDY: This study aimed to elucidate the therapeutic effects, pharmacodynamic material bases, and mechanisms of V. dunalianum buds on diet-induced hyperlipidemia. MATERIALS AND METHODS: A high-fat diet-induced hyperlipidemic Sprague-Dawley (SD) rat model was established. Rats were gavaged with different doses of aqueous extract of V. dunalianum(VDW) for 8 weeks and their sera and organ samples were collected. The antihyperlipidemic effect of VDW on SD rats was evaluated based on the biochemical indices and histopathological outcomes. Liquid chromatography-mass spectrometry(LC-MS) was used to determine the main components in VDW, which were separated and purified using sequential chromatographic methods. Their chemical structures were determined using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. 6'-O-caffeoyl-arbutin, as the principal component of VDW, was also evaluated for its antihyperlipidemic activity using an approach similar to that used for VDW. Lastly, the potential targets of VDW and 6'-O-caffeoyl-arbutin in lowering blood lipids were screened out using network pharmacology, and the selected targets were docked with arbutin derivatives. The expression of target proteins was determined using western blotting to illustrate the antihyperlipidemic mechanisms of VDW and 6'-O-caffeoyl-arbutin. RESULTS: VDW reduced triglyceride, total cholesterol, low-density lipoprotein, alanine transaminase, and aspartate transaminase levels in the serum of modeled rats, and increased high-density lipoprotein levels. There was an improvement in steatoses, and lipid droplet accumulation decreased in vivo after VDW intervention. LC-MS revealed that VDW mainly contained arbutin and chlorogenic acid derivatives. Sixteen compounds were isolated and identified. 6'-O-caffeoyl-arbutin was the main compound of VDW (>21.67%) that showed obvious antihyperlipidemic effect with low hepatic damage at different doses. PTGS2, ADH1C, and MAOB were screened out using network pharmacology and they showed strong correlations with arbutin derivative through molecular docking. Results from WB showed that VDW and 6'-O-caffeoyl-arbutin could reduce blood lipid levels by reducing the protein expression of PTGS2, ADH1C, and MAOB. CONCLUSIONS: 6'-O-caffeoyl-arbutin was the main component of V. dunalianum buds. VDW and 6'-O-caffeoyl-arbutin could regulate blood lipid levels in the high-fat diet-induced rat model of hyperlipidemia without damaging their vital organs. Furthermore, they could regulate the expression of PTGS2, ADH1C, and MAOB proteins and play a role in lowering blood lipids. The findings of this study lay a foundation for the further development of V. dunalianum and 6'-O-caffeoyl-arbutin as health supplements or drugs for the management of hyperlipidemia.