Enhancing X-Ray Sensitization with Multifunctional Nanoparticles.

In the progression of X-ray-based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.

Long-Lived Phosphorescent Carbon Dots as Photosensitizers for Total Antioxidant Capacity Assay.

Free radicals and their induced oxidative damage in living organisms are related to many diseases. Natural substances with antioxidant capacity are effective in scavenging free radicals, which could slow down aging and prevent diseases. However, the existing methods for the evaluation of antioxidant activity mostly required the use of complex instruments and operations. In this work, we proposed a unique method to determine the total antioxidant capacity (TAC) in real samples through a photosensitization-mediated oxidation system. N- and P-doped long-lived phosphorescent carbon dots (NPCDs) were developed, which exhibited the effective intersystem crossing from the singlet to the triplet state under UV light irradiation. Mechanism study confirmed that the energy of excited triplet state in NPCDs generated superoxide radicals and singlet oxygen through type I and type II photoreactions, respectively. On this basis, the quantitative determination of TAC in fresh fruits was achieved using 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic bridge in the photosensitization-mediated oxidation system. This demonstration will not only provide a facile way to analyze antioxidant capacity in practical samples but also broaden the applications of phosphorescent carbon dots.

Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma.

BACKGROUND: Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS: Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS: Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS: We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).

Piceatannol Alleviates Clostridium perfringens Virulence by Inhibiting Perfringolysin O.

Clostridium perfringens (C. perfringens) is an important foodborne pathogen that can cause diseases such as gas gangrene and necrotizing enteritis in a variety of economic animals, seriously affecting public health and the economic benefits and healthy development of the livestock and poultry breeding industry. Perfringolysin O (PFO) is an important virulence factor of C. perfringens and plays critical roles in necrotic enteritis and gas gangrene, rendering it an ideal target for developing new drugs against infections caused by this pathogen. In this study, based on biological activity inhibition assays, oligomerization tests and computational biology assays, we found that the foodborne natural component piceatannol reduced pore-forming activity with an inhibitory ratio of 83.84% in the concentration of 16 µg/mL (IC50 = 7.83 µg/mL) by binding with PFO directly and changing some of its secondary structures, including 3-Helix, A-helix, bend, and in turn, ultimately affecting oligomer formation. Furthermore, we confirmed that piceatannol protected human intestinal epithelial cells from the damage induced by PFO with LDH release reduced by 38.44% at 16 µg/mL, based on a cytotoxicity test. By performing an animal experiment, we found the C. perfringens clones showed an approximate 10-fold reduction in infected mice. These results suggest that piceatannol may be a candidate for anti-C. perfringens drug development.

Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis.

PURPOSE: Cardiotoxicity affects 5-16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. METHODS: A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran's Q test and the I2 test. RESULTS: Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27-0.78), p = 0.004, [Formula: see text] = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17-1.45), p = 0.20, [Formula: see text] = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75-9.52), p < 0.001, [Formula: see text] = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82-11.68, p = 0.024, [Formula: see text] = 80.9%]. We were unable to explore publication bias due to the small number of studies. CONCLUSION: This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: PROSPERO: CRD42020140352 on 7/6/2020.

Molecular dynamics investigation on the interaction of human angiotensin-converting enzyme with tetrapeptide inhibitors.

Angiotensin-converting enzyme (ACE) is a well-known zinc metalloenzyme whose physiological functions are vital to blood pressure regulation and management of hypertension. The development of more efficient peptide inhibitors is of great significance for the prevention and treatment of hypertension. In this research, molecular dynamics (MD) simulations were implemented to study the specific binding mechanism and interaction between human ACE (hACE) and tetrapeptides, YIHP, YKHP, YLVR, and YRHP. The calculation of relative binding free energy on the one hand verified that YLVR, an experimentally identified inhibitor, has a stronger inhibitory effect and, on the other hand, indicated that YRHP is the "best" inhibitor with the strongest binding affinity. Inspection of atomic interactions discriminated the specific binding mode of each tetrapeptide inhibitor with hACE and explained the difference of their affinity. Moreover, in-depth analysis of the MD production trajectories, including clustering, principal component analysis, and dynamic network analysis, determined the dynamic correlation between tetrapeptides and hACE and obtained the communities' distribution of a protein-ligand complex. The present study provides essential insights into the binding mode and interaction mechanism of the hACE-peptide complex, which paves a path for designing effective anti-hypertensive peptides.

PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma.

Lung adenocarcinoma (LUAD), as a form of non-small cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer worldwide. To date, a few biomarkers have been reported to provide valuable information in guiding LUAD treatment. The aim of our study was to explore the functional role of pyrroline-5-carboxylate reductase 1 (PYCR1) in LUAD. Based on Oncomine database, we found that PYCR1 was highly expressed in LUAD tissues. We also confirmed an abnormal increase of PYCR1 expression in LUAD cell lines and patients' tissues. Through Kaplan-Meier plotter database, we further studied the prognostic values of PYCR1. The outcomes indicated that overexpressed PYCR1 associated with poor prognosis among LUAD patients. To further study the function of PYCR1 in LUAD, cell counting kit-8, colony-forming, scratch wound healing, and Transwell assays were conducted. The results suggested that knockdown of PYCR1 curbed cell proliferation, migration, and invasion in LUAD cell lines. Subsequently, we identified 50 top genes positively and negatively correlated with PYCR1 in LUAD, and conducted biological pathway enrichment analysis of these genes. Among those enriched pathways, we selected JAK/STAT signaling pathway for further analysis. The results of Western blot assays revealed that PYCR1 knockdown significantly increased the expression of Bcl-2 and c-Myc, and the phosphorylation level of JAK2 and STAT3. Taken together, this study unearthed that PYCR1 knockdown could inhibit tumor growth and affect the JAK/STAT signaling pathway in LUAD. This study may contribute to a better understanding of PYCR1 in LUAD and provide a potential biomarker for cancer prognosis.

Discovery of the Novel Inhibitor Against New Delhi Metallo-ß-Lactamase Based on Virtual Screening and Molecular Modelling.

New Delhi metallo-ß-lactamase (NDM-1), one of the metallo-ß-lactamases (MBLs), leads to antibiotic resistance in clinical treatments due to the strong ability of hydrolysis to almost all kinds of ß-lactam antibiotics. Therefore, there is the urgent need for the research and development of the novel drug-resistant inhibitors targeting NDM-1. In this study, ZINC05683641 was screened as potential NDM-1 inhibitor by virtual screening and the inhibitor mechanism of this compound was explored based on molecular dynamics simulation. The nitrocefin assay showed that the IC50 value of ZINC05683641 was 13.59 ± 0.52 µM, indicating that the hydrolytic activity of NDM-1 can be obviously suppressed by ZINC05683641. Further, the binding mode of ZINC05683641 with NDM-1 was obtained by molecular modeling, binding free energy calculation, mutagenesis assays and fluorescence-quenching assays. As results, ILE-35, MET-67, VAL-73, TRP-93, CYS-208, ASN-220 and HIS-250 played the key roles in the binding of NDM-1 with ZINC05683641. Interestingly, these key residues were exactly located in the catalytic activity region of NDM-1, implying that the inhibitor mechanism of ZINC05683641 against NDM-1 was the competitive inhibition. These findings will provide an available approach to research and develop new drug against NDM-1 and treatment for bacterial resistance.

Correction to: Phloretin reduces cell injury and inflammation mediated by Staphylococcus aureus via targeting sortase B and the molecular mechanism.

The images of cells under microscope in Figure 2 and Figure S2 were misused from Wang G et al. Front Cell Infect Microbiol. 2018 Nov 30;8:418. These images were generated in the same set of assays.

Phloretin reduces cell injury and inflammation mediated by Staphylococcus aureus via targeting sortase B and the molecular mechanism.

Sortase B (SrtB) is a vital virulence factor that plays a critical role in Staphylococcus aureus (S. aureus) infections, indicating that it could be a latent target for S. aureus infections. In this study, phloretin, a natural compound that primarily exists in the pericarp and velamen of apples and pears, shows little anti-S. aureus activity, but significantly inhibited SrtB activity in vitro. The results of lactate dehydrogenase release and live/dead cell assays suggested that phloretin reduced human alveolar epithelial cell damage caused by S. aureus. Additionally, an adhesion assay confirmed that phloretin lowered the colony count of S. aureus in human alveolar cells. Phloretin treatment significantly attenuated the inflammatory response in macrophage cells (J774) co-cultured with S. aureus as determined by an enzyme-linked immune-sorbent assay. Furthermore, the results of molecular dynamics simulation, site-directed mutagenesis, and fluorescence spectroscopy quenching indicated that phloretin was directly located in the active pocket of SrtB and blocked substrate binding, leading to the loss of SrtB activity. These results indicate that phloretin is a possible candidate for treatment of S. aureus infections.

Novel Inhibitor Discovery of Staphylococcus aureus Sortase B and the Mechanism Confirmation via Molecular Modeling.

SortaseB (SrtB) plays a critical role in Staphylococcus aureus (S. aureus) infections. According to the reports in the literature, SrtB can anchor the IsdC to the cell wall to capture iron from the host to achieve a successful invasion. On the other hand, SrtB could also affect the adhesion of S. aureus to host cells based on previous studies. Here, we report about a novel SrtB inhibitor, coptisine, a natural compound that does not exhibit antibacterial activity but can inhibit the SrtB activity in vitro. A cytotoxicity test indicated that coptisine protects human lung epithelial cells from S. aureus. In addition, coptisine can reduce the adhesion of S. aureus to human lung epithelial cells based on the result of plate colony counting assay. Molecular dynamics simulation revealed that coptisine can bind to the active pocket of SrtB, leading to its activity loss. Through the calculation of binding free energy between ligand and protein, site-directed mutagenesis and fluorescence spectroscopy quenching methods, it was confirmed that residues of Arg115, Asn116, and Ile182 played a vital role in the interaction of SrtB with coptisine. These data provide the theoretical basis for the therapy option to the infections caused by S. aureus.

Serum high-density lipoprotein correlates with serum apolipoprotein M and A5 in obstructive sleep apnea hypopnea syndrome.

PURPOSE: The purpose of this study was to investigate the correlation between serum levels of serum apolipoprotein M (ApoM), A5 (ApoA5), and high-density lipoprotein (HDL) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and study the effects of nasal continuous positive airway pressure treatment on these serum biomarkers. METHODS: Thirty OSAHS patients and 15 non-OSAHS probands as control were selected for the study. Serum HDL, ApoM, and ApoA5 levels in two groups were detected; differences and association among them were analyzed. Patients with moderate and severe OSAHS underwent 3-month auto-continuous positive airway pressure treatment, and a comparative study was conducted to investigate the changes in blood lipids, serum ApoM, and ApoA5. RESULTS: In comparison to the control group, the HDL, ApoM, and ApoA5 serum levels were lower (P < 0.05). HDL was positively correlated to ApoM and ApoA5 (P < 0.001), and ApoM was positively correlated to ApoA5 (r = 0.536, P < 0.001). HDL, ApoM, and ApoA5 were significantly increased in the patients of moderate and severe OSAHS after auto-continuous positive airway pressure treatment for 3 months (P < 0.05). CONCLUSIONS: The HDL level was significantly lower in OSAHS patients. The decrease in serum ApoM and ApoA5 in OSAHS patients was correlated to the severity of OSAHS and HDL levels. Auto-continuous positive airway pressure treatment increased serum levels of ApoM, ApoA5, and HDL in OSAHS patients.

[Mechanisms for inhibitory effect of ALDH2 on doxorubicin-induced cytotoxicity in C2C12 myogenic cell line].

OBJECTIVE: To investigate the mechanisms for inhibitory effect of aldehyde dehydrogenase 2 (ALDH2) on doxorubicin (DOX)-induced cytotoxicity in C2C12 myogenic cell line.
 METHODS: Cell apoptosis was evaluated by flow cytometry and the activity of capase-3/7. The relative content of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) were detected by chemical fluorometric enzyme immunoassay. The protein and mRNA expression of ALDH2, Bcl-2, NADPH oxidase 2 (NOX2) and the cytoplasmic subunit p-p47PHOX were evaluated by Western blot and quantitative PCR, respectively. 
 RESULTS: Overexpression of ALDH2 attenuated DOX-induced cell toxicity (increase in apoptosis and inhibition of proliferation), which were reversed by downregulation of ALDH2. Overexpression of ALDH2 reduced p47PHOX phosphorylation levels, and suppressed activation of NOX2 and ROS production, which were reversed by downregulation of ALDH2. Moreover, apocynin, an inhibitor of NOX, reduced the cytotoxicity of DOX concomitantly with a decrease in phosphorylation of p47PHOX, ROS production and caspase-3/7 activity, and an increase in the activity and expression of ALDH2. 
 CONCLUSION: DOX-induced cytotoxicity is related to increase of intracellular oxidative stress, which is involved in unregulation of NOX2 and downregulation of ALDH2. Activation of ALDH2 could exert cytoprotection via inhibiting NOX2-dependent ROS production.

A hydrogen-bonded curdlan-chitosan/polyvinyl alcohol edible dual functional hydrogel bandage against MRSA promotes wound healing.

The most prevalent complication arising from skin injuries is bacterial infection, where pathogenic bacteria proliferate significantly at the wound site, leading to subsequent complications like septic shock and sepsis. Although antibiotics presently effectively manage wound infections caused by common bacteria, the escalating prevalence of antibiotic-resistant strains necessitates urgent novel approaches for addressing such infections. Here, we present CS9P1-RA, a dual functional hydrogel dressing, based on polyvinyl alcohol (PVA) matrix crosslinked through hydrogen bonding. CS9P1-RA combines chitosan (CS), a food-derived antibacterial agent, with the natural compound rosmarinic acid (RA) to specifically target skin injuries caused by MRSA. Computational and molecular biology assays illustrate RA's ability to selectively inhibit the activity of Staphylococcus aureus (S. aureus) serine/threonine phosphatase (Stp1), reducing the S. aureus pathogenicity. CS9P1-RA showcases exceptional antibacterial efficacy (MIC = 1 mg/mL) and demonstrates potency in reducing virulence (IC50 = 7.424 µM on Stp1). Notably, it effectively curbs bacterial growth and accelerates wound healing in the mice model, thereby fulfilling the practical requirements for clinical applications. Moreover, the mechanical properties of CS9P1-RA ensure user comfort during treatment. This work introduces a fresh design paradigm for dressing materials, offering a promising solution for treating skin injuries inflicted by antibiotic-resistant bacterial infections.

Isolation, Virtual Screening, and Evaluation of Hazelnut-Derived Immunoactive Peptides for the Inhibition of SARS-CoV-2 Main Protease.

The aim of this study is to validate the activity of hazelnut (Corylus avellana L.)-derived immunoactive peptides inhibiting the main protease (Mpro) of SARS-CoV-2 and further unveil their interaction mechanism using in vitro assays, molecular dynamics (MD) simulations, and binding free energy calculations. In general, the enzymatic hydrolysis components, especially molecular weight < 3 kDa, possess good immune activity as measured by the proliferation ability of mouse splenic lymphocytes and phagocytic activity of mouse peritoneal macrophages. Over 866 unique peptide sequences were isolated, purified, and then identified by nanohigh-performance liquid chromatography/tandem mass spectrometry (NANO-HPLC-MS/MS) from hazelnut protein hydrolysates, but Trp-Trp-Asn-Leu-Asn (WWNLN) and Trp-Ala-Val-Leu-Lys (WAVLK) in particular are found to increase the cell viability and phagocytic capacity of RAW264.7 macrophages as well as promote the secretion of the cytokines nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). Fluorescence resonance energy transfer assay elucidated that WWNLN and WAVLK exhibit excellent inhibitory potency against Mpro, with IC50 values of 6.695 and 16.750 µM, respectively. Classical all-atom MD simulations show that hydrogen bonds play a pivotal role in stabilizing the complex conformation and protein-peptide interaction. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculation indicates that WWNLN has a lower binding free energy with Mpro than WAVLK. Furthermore, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions illustrate favorable drug-likeness and pharmacokinetic properties of WWNLN compared to WAVLK. This study provides a new understanding of the immunomodulatory activity of hazelnut hydrolysates and sheds light on peptide inhibitors targeting Mpro.

Tissue-Resident Memory T Cells in Allergy.

Tissue-resident memory T (TRM) cells constitute a distinct subset within the memory T cell population, serving as the vanguard against invading pathogens and antigens in peripheral non-lymphoid tissues, including the respiratory tract, intestines, and skin. Notably, TRM cells adapt to the specific microenvironment of each tissue, predominantly maintaining a sessile state with distinctive phenotypic and functional attributes. Their role is to ensure continuous immunological surveillance and protection. Recent findings have highlighted the pivotal contribution of TRM cells to the modulation of adaptive immune responses in allergic disorders such as allergic rhinitis, asthma, and dermatitis. A comprehensive understanding of the involvement of TRM cells in allergic diseases bears profound implications for allergy prevention and treatment. This review comprehensively explores the phenotypic characteristics, developmental mechanisms, and functional roles of TRM cells, focusing on their intricate relationship with allergic diseases.

Novel metallo-ß-lactamases inhibitors restore the susceptibility of carbapenems to New Delhi metallo-lactamase-1 (NDM-1)-harbouring bacteria.

BACKGROUND AND PURPOSE: The production of metallo-ß-lactamases is a major mechanisms adopted by bacterial pathogens to resist carbapenems. Repurposing approved drugs to restore the efficacy of carbapenems represents an efficient and cost-effective approach to fight infections caused by carbapenem resistant pathogens. EXPERIMENTAL APPROACH: The nitrocefin hydrolysis assay was employed to screen potential New Delhi metallo-lactamase-1 (NDM-1) inhibitors from a commercially available U.S. Food and Drug Administration (FDA) approved drug library. The mechanism of inhibition was clarified by metal restoration, inductively coupled plasma mass spectrometry (ICP-MS) and molecular dynamics simulation. The in vitro synergistic antibacterial effect of the identified inhibitors with meropenem was determined by the checkerboard minimum inhibitory concentration (MIC) assay, time-dependent killing assay and combined disc test. Three mouse infection models were used to further evaluate the in vivo therapeutic efficacy of combined therapy. KEY RESULTS: Twelve FDA-approved compounds were initially screened to inhibit the ability of NDM-1 to hydrolyse nitrocefin. Among these compounds, dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid were demonstrated to inhibit all tested metallo-ß-lactamases and showed an in vitro synergistic bactericidal effect with meropenem against metallo-ß-lactamases-producing bacteria. Dexrazoxane, embelin and candesartan cilexetil are metal ion chelating agents, while the inhibition of NDM-1 by nordihydroguaiaretic acid involves its direct binding to the active region of NDM-1. Furthermore, these four drugs dramatically rescued the treatment efficacy of meropenem in three infection models. CONCLUSIONS AND IMPLICATIONS: Our observations indicated that dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid are promising carbapenem adjuvants against metallo-ß-lactamases-positive carbapenem resistant bacterial pathogens.

Identification of a novel prognostic signature based on vitamin metabolism clustering-related genes in lung adenocarcinoma.

Background: Vitamins, and their metabolic processes play essential regulatory roles in controlling proliferation, differentiation, and growth in carcinogenesis. However, the role of vitamin metabolism in lung adenocarcinoma (LUAD) has rarely been reported. Here, we established a novel prognostic model based on vitamin metabolism-related genes in LUAD. Methods: In this research, we aimed to identify vitamin metabolism associated with differentially expressed genes (DEGs) in LUAD utilizing The Cancer Genome Atlas (TCGA)-LUAD, GSE68465 and GSE72094 data. Unsupervised clustering classified patients into distinct subgroups. By utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis, vitamin metabolism-related genes could be used to construct prognostic model. Then the vitamin metabolism gene-related risk score (VRS) was calculated based on best cut-off splitting. Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) analysis, univariate and multivariate Cox analyses, chemotherapeutic drugs sensitivity analysis, immune infiltration analysis and nomogram were conducted to verify our models' accuracy. Finally, CPS1 was identified as a relevant diagnostic marker using Random Forests algorithms, single-cell RNA sequencing data was used to confirm its expression. Results: We investigated the relationship between vitamin metabolism patterns, overall survival (OS), and immune infiltration levels of patients with LUAD. A prognostic signature consisting of 11 genes was developed, which was able to classify patients into high and low VRS groups. Through gene enrichment analysis, cell cycle was mainly enriched. Compared to the low VRS group, the high VRS group exhibited poorer OS, as demonstrated by the Kaplan-Meier survival analysis. Furthermore, VRS was identified as an independent predictor of poor prognosis and poor OS, as indicated by both univariate and multivariate Cox regression analyses. Additionally, a nomogram was constructed to improve the accuracy of survival predictions in LUAD patients. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs. CPS1 was identified as a relevant diagnostic marker and the expression was also as confirmed by single-cell RNA sequencing data. Conclusions: Overall, our findings suggest that vitamin metabolism can influence the prognosis of LUAD patients, and our prognostic signature represents a potentially helpful resource for predicting patient outcomes and informing clinical decision-making.