Research trends in lipid-lowering therapies for coronary heart disease combined with hyperlipidemia: a bibliometric study and visual analysis.

Background: Cardiovascular disease (CVD) poses a significant global health and economic challenge, with atherosclerosis being a primary cause. Over the past 40 years, substantial research has been conducted into the prevention and reversal of atherosclerosis, resulting in the development of lipid-lowering agents such as statins and fibrates. Despite the extensive literature and formulation of numerous therapeutic guidelines in this domain, a comprehensive bibliometric analysis of the current research landscape and trends has not been performed. This study aimed to elucidate the evolution and milestones of research into lipid-lowering treatments for coronary heart disease (CHD) in conjunction with hyperlipidemia through bibliometric analysis, offering insights into future directions for treatment strategies. Methods: This study examined publications from 1986 to 2023 retrieved from the Web of Science database (Core Collection). Utilizing tools such as VOSviewer, Pajek, and CiteSpace, we analyzed publication and citation numbers, H-indexes, contributions by countries and institutions, authorship, journal sources, and keyword usage to uncover research trajectories and areas of focus. Results: Our analysis of 587 publications revealed a recent surge in research output, particularly post-2003. The American Journal of Cardiology published the highest number of studies, with 40 articles, whereas Circulation received the highest number of citations (6,266). Key contributors included the United States, Japan, and China, with the United States leading in citation numbers and the H-index. Harvard University and Leiden University emerged as pivotal institutions, and Professors J. Wouter Jukema and Robert P. Giugliano were identified as leading experts. Keyword analysis disclosed five thematic clusters, indicating a shift in research towards new drug combinations and strategies, signaling future research directions. Conclusion: The last 4 decades have seen a notable rise in publications on lipid-lowering therapies for CHD and hyperlipidemia, with the United States retaining world-leading status. The increase in international collaboration aids the shift towards research into innovative lipid-lowering agents and therapeutic approaches. PCSK9 inhibitors and innovative combination therapies, including antisense oligonucleotides and angiopoietin-like protein 3 inhibitors, provide avenues for future research, intending to maximize the safety and efficacy of treatment approaches.

Advanced Glycation End Products and Health: A Systematic Review.

Advanced glycation end products (AGEs) have garnered significant attention due to their association with chronic diseases and the aging process. The prevalence of geriatric diseases among young individuals has witnessed a notable surge in recent years, potentially attributed to the accelerated pace of modern life. The accumulation of AGEs is primarily attributed to their inherent difficulty in metabolism, which makes them promising biomarkers for chronic disease detection. This review aims to provide a comprehensive overview of the recent advancements and findings in AGE research. The discussion is divided into two main sections: endogenous AGEs (formed within the body) and exogenous AGEs (derived from external sources). Various aspects of AGEs are subsequently summarized, including their production pathways, pathogenic mechanisms, and detection methods. Moreover, this review delves into the future research prospects concerning AGEs. Overall, this comprehensive review underscores the importance of AGEs in the detection of chronic diseases and provides a thorough understanding of their significance. It emphasizes the necessity for further research endeavors to deepen our comprehension of AGEs and their implications for human health.

Nanoporous Carbon Materials Derived from Zanthoxylum Bungeanum Peel and Seed for Electrochemical Supercapacitors.

In order to prepare biomass-derived carbon materials with high specific capacitance at a low activation temperature (≤700 °C), nanoporous carbon materials were prepared from zanthoxylum bungeanum peels and seeds via the pyrolysis and KOH-activation processes. The results show that the optimal activation temperatures are 700 °C and 600 °C for peels and seeds. Benefiting from the hierarchical pore structure (micropores, mesopores, and macropores), the abundant heteroatoms (N, S, and O) containing functional groups, and plentiful electrochemical active sites, the PAC-700 and SAC-600 derive the large capacities of ~211.0 and ~219.7 F g-1 at 1.0 A g-1 in 6 M KOH within the three-electrode configuration. Furthermore, the symmetrical supercapacitors display a high energy density of 22.9 and 22.4 Wh kg-1 at 7500 W kg-1 assembled with PAC-700 and SAC-600, along with exceptional capacitance retention of 99.1% and 93.4% over 10,000 cycles at 1.0 A g-1. More significantly, the contribution here will stimulate the extensive development of low-temperature activation processes and nanoporous carbon materials for electrochemical energy storage and beyond.

On the modification of plant proteins: Traditional methods and the Hofmeister effect.

With increasing consumer health awareness and demand from some vegans, plant proteins have received a lot of attention. Plant proteins have many advantages over animal proteins. However, the application of plant proteins is limited by a number of factors and there is a need to improve their functional properties to enable a wider range of applications. This paper describes the advantages and disadvantages of traditional methods of modifying plant proteins and the appropriate timing for their use, and collates and describes a method with fewer applications in the food industry: the Hofmeister effect. It is extremely simple but efficient in some respects compared to traditional methods. The paper provides theoretical guidance for the further development of plant protein-based food products and a reference value basis for improving the functional properties of proteins to enhance their applications in the food industry, pharmaceuticals and other fields.

Chemical constituents from uncaria laevigata and their vasodilatory activities in vitro and action mechanism.

A new triterpenoid compound 1* (scandine A1) was obtained from 95% ethanol extract of Uncaria laevigata. Meanwhile, eleven described compounds were also isolated for the first time from Uncaria laevigata. Herein, compound 2 exhibited strong diastolic cardio-cerebrovascular activity (EC50BA = 9.22 µM and EC50CA = 14.65 µM), which was not been previously described. Compound 1* also showed certain diastolic cardio-cerebrovasculary activity. Network pharmacology indicated that the diastolic cardio-cerebrovascular activity of compound 2 was most correlated with the Ras signalling pathway. Molecular docking confirmed that it exhibited strong binding activity with target protein (matrix metalloproteinase inhibitor-1). Moreover, compound 2 demonstrated significant potential on cardio-cerebrovascular activity in vitro. Overall, compounds 1* and 2 with good diastolic cardio-cerebrovascular activity were discovered in this work.

Achieving Highly Stable Zn Metal Anodes at Low Temperature via Regulating Electrolyte Solvation Structure.

Zinc metal is an attractive anode material for rechargeable aqueous Zn-ion batteries (ZIBs). However, the dendrite growth, water-induced parasitic reactions, and freezing problem of aqueous electrolyte at low temperatures are the major roadblocks that hinder the widely commercialization of ZIBs. Herein, tetrahydrofuran (THF) is proposed as the electrolyte additive to improve the reversibility and stability of Zn anode. Theoretical calculation and experimental results reveal that the introduction of THF into the aqueous electrolyte can optimize the solvation structure which can effectively alleviate the H2O-induced side reactions and protect the Zn anode from corrosion. Moreover, THF can act as a hydrogen bond acceptor to interact with H2O, which can greatly reduce the activity of free H2O in electrolytes and improve the low-temperature electrochemical performance of Zn anode. As a result, the Zn anodes demonstrate high cyclic stability for 2800 h at 27 °C and over 4000 h at -10 °C at 1.0 mA cm-2 /1.0 mAh cm-2. The full cell exhibits excellent cyclic stability and rate capability at 27 and -10 °C. This work is expected to provide a new approach to regulate the aqueous electrolyte and Zn anode interface chemistry for highly stable and reversible Zn anodes.

SLC27A2 is a potential immune biomarker for hematological tumors and significantly regulates the cell cycle progression of diffuse large B-cell lymphoma.

BACKGROUND: Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported. METHOD: This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors. RESULT: This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells. CONCLUSION: In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.

A Novel NIR Fluorescence Probe with AIE Property to Image Viscosity in Nystatin-Induced Cell Model.

As one of the most significant parameters in cellular microenvironment, viscosity levels could be used to determine the metabolic process of bioactive substances within cells. Abnormal viscosity levels are closely associated with a series of diseases. Therefore, the design and synthesis of fluorescent probes that can monitor changes of intracellular viscosity in real-time is of great significance for the study of disease development process. Here, a new viscosity-recognized NIR fluorescence probe W1 based on quinoline-malonitrile is synthesized, and it is not susceptible to interference substances. Besides, AIE probe W1 shows fast response, excellent photostability, low cytotoxicity, good linear relationship between fluorescence intensity value and viscosity. Based on the above advantages, probe W1 is used to image the change of viscosity level in the cell model induced by nystatin.

Contact-electro-catalysis (CEC).

Contact-electro-catalysis (CEC) is an emerging field that utilizes electron transfer occurring at the liquid-solid and even liquid-liquid interfaces because of the contact-electrification effect to stimulate redox reactions. The energy source of CEC is external mechanical stimuli, and solids to be used are generally organic as well as in-organic materials even though they are chemically inert. CEC has rapidly garnered extensive attention and demonstrated its potential for both mechanistic research and practical applications of mechanocatalysis. This review aims to elucidate the fundamental principle, prominent features, and applications of CEC by compiling and analyzing the recent developments. In detail, the theoretical foundation for CEC, the methods for improving CEC, and the unique advantages of CEC have been discussed. Furthermore, we outline a roadmap for future research and development of CEC. We hope that this review will stimulate extensive studies in the chemistry community for investigating the CEC, a catalytic process in nature.

Opportunities and perspectives of small molecular phosphodiesterase inhibitors in neurodegenerative diseases.

Phosphodiesterase (PDE) is a superfamily of enzymes that are responsible for the hydrolysis of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). PDE inhibition promotes the gene transcription by activating cAMP-response element binding protein (CREB), initiating gene transcription of brain-derived neurotrophic factor (BDNF). The procedure exerts neuroprotective profile, and motor and cognitive improving efficacy. From this point of view, PDE inhibition will provide a promising therapeutic strategy for treating neurodegenerative disorders. Herein, we summarized the PDE inhibitors that have entered the clinical trials or been discovered in recent five years. Well-designed clinical or preclinical investigations have confirmed the effectiveness of PDE inhibitors, such as decreasing Aß oligomerization and tau phosphorylation, alleviating neuro-inflammation and oxidative stress, modulating neuronal plasticity and improving long-term cognitive impairment.

Phthalate ester (PAEs) accumulation in wheat tissues and dynamic changes of rhizosphere microorganisms in the field with plastic-film residue.

Phthalates acid esters (PAEs) have accumulated in soil and crops like wheat as a result of the widespread usage of plastic films. It is yet unclear, nevertheless, how these dynamic variations in PAE accumulation in wheat tissues relate to rhizosphere bacteria in the field. In this work, a field root-bag experiment was conducted to examine the changes of PAEs accumulation in the rhizosphere soil and wheat tissues under film residue conditions at four different growth stages of wheat, and to clarify the roles played by the microbial community in the alterations. Results showed that the plastic film residues significantly increased the concentrations of PAEs in soils, wheat roots, straw and grains. The maximum ΣPAEs concentration in soils and different wheat tissues appeared at the maturity, with the ΣPAEs concentration of 1.57 mg kg-1, 4.77 mg kg-1, 5.21 mg kg-1, 1.81 mg kg-1 for rhizosphere soils, wheat roots, straw and grains, respectively. The plastic film residues significantly changed the functions and components of the bacterial community, increased the stochastic processes of the bacterial community assembly, and reduced the complexity and stability of the bacterial network. In addition, the present study identified some bacteria associated with plastic film residues and PAEs degradation in key-stone taxa, and their relative abundances were positive related to the ΣPAEs concentration in soils. The PAEs content and key-stone taxa in rhizosphere soil play a crucial role in the formation of rhizosphere soil bacterial communities. This field study provides valuable information for better understanding the role of microorganisms in the complex system consisting of film residue, soil and crops.

The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions.

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human-induced pluripotent stem cells (hiPSCs), reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signaling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism that cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration.

The protective effects of ligustrazine on ischemic stroke: a systematic review and meta-analysis of preclinical evidence and possible mechanisms.

Introduction: The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action. Materials and Methods: The intervention of ligustrazine in ischemic diseases research on stroke model animals was searched in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP Database (VIP), Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and Embase databases. The quality of the included literature was evaluated using the Cochrane risk of bias tool. The evaluation included measures such as neurological deficit score (NDS), percentage of cerebral infarction volume, brain water content, inflammation-related factors, oxidative stress-related indicators, apoptosis indicators (caspase-3), and blood-brain barrier (BBB) permeability (Claudin-5). Results: A total of 32 studies were included in the analysis. The results indicated that ligustrazine significantly improved the neurological function scores of ischemic stroke animals compared to the control group (SMD = -1.84, 95% CI -2.14 to -1.55, P < 0.00001). It also reduced the percentage of cerebral infarction (SMD = -2.97, 95% CI -3.58 to -2.36, P < 0.00001) and brain water content (SMD = -2.37, 95% CI -3.63 to -1.12, P = 0.0002). In addition, ligustrazine can significantly improve various inflammatory factors such as TNF-α (SMD = -7.53, 95% CI -11.34 to -3.72, P = 0.0001), IL-1ß (SMD = -2.65, 95% CI -3.87 to -1.44, P < 0.0001), and IL-6 (SMD = -5.55, 95% CI -9.32 to -1.78, P = 0.004). It also positively affects oxidative stress-related indicators including SOD (SMD = 4.60, 95% CI 2.10 to 7.10, P = 0.0003), NOS (SMD = -1.52, 95% CI -2.98 to -0.06, P = 0.04), MDA (SMD = -5.31, 95% CI -8.48 to -2.14, P = 0.001), and NO (SMD = -5.33, 95% CI -8.82 to -1.84, P = 0.003). Furthermore, it shows positive effects on the apoptosis indicator caspase-3 (SMD = -5.21, 95% CI -7.47 to -2.94, P < 0.00001) and the expression level of the sex-related protein Claudin-5, which influences BBB permeability (SMD = 7.38, 95% CI 3.95 to 10.82, P < 0.0001). Conclusion: Ligustrazine has been shown to have a protective effect in animal models of cerebral ischemic injury. Its mechanism of action is believed to be associated with the reduction of inflammation and oxidative stress, the inhibition of apoptosis, and the repair of BBB permeability. However, further high-quality animal experiments are required to validate these findings.

Effect of Placental Transfusion on Long-Term Neurodevelopmental Outcomes in Premature Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. METHODS: We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. RESULTS: A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. CONCLUSIONS: From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.

Optimization of Bear Oil Extraction Process and Hair Growth Activity.

According to ancient Chinese books, bear grease has the effects of strengthening muscles and bones, which is beneficial for weakness, but there is relatively little research on it. Thus, the extraction of it is beneficial for compensating for research in this area. In this study, a uniform experimental design method was used to optimize the extraction process of bear grease by enzymatic hydrolysis extraction, and the extraction rate can reach 81.89% under optimized extraction conditions. Furthermore, the components of bear grease obtained by this study were analyzed by GC-MS, and the results showed that ursolic oil was rich in unsaturated fatty acids (67.51%), which was higher than that of the traditional method (66.92%). The composition of bear grease extracted by the enzymatic method was also better than that extracted by the traditional method. In addition, bear grease obtained in this study had the obvious activity of promoting hair growth. The length, weight, and number of hair follicles in the depilation area of mice in the high-dose group were significantly different from those in the blank group (p < 0.01). This study optimized the extraction process of bear grease and conducted a preliminary analysis of its fatty acid composition, which is expected to provide some reference for the development of the medicinal value of bear grease.

The Influence of Mindful Parenting on Children's Creative Tendencies: The Chain Mediating Effect of Parent-Child Intimacy and Connectedness to Nature.

(1) Objectives: The aim of this study was to examine the relationship between mindful parenting and children's creative tendencies and to investigate the mediating role of parent-child intimacy and connectedness to nature in the relationship between mindful parenting and children's creative tendencies. (2) Methods: In this cross-sectional study, nearly 800 mothers of children aged 3-6 were enrolled. General sociodemographic data, the Mindfulness in Parenting Questionnaire (MIPQ), the Creativity Assessment Packet (CAP), the Child-Parent Relationship Scale-Short Form (CPRS-SF), and the Connectedness to Nature Index-Parents of Preschool Children (CNI-PPC) were all included in the questionnaire survey. (3) Results: There were significant positive correlations among mindful parenting, parent-child intimacy, connectedness to nature, and children's creative tendencies. Mindful parenting had a positive predictive effect on children's creative tendencies. Parent-child intimacy played a mediating role between mindful parenting and children's creative tendencies. Connectedness to nature played a mediating role between mindful parenting and children's creative tendencies. The correlation between mindful parenting and children's creative tendencies may be impacted by the chain mediation effects of parent-child intimacy and connectedness to nature. (4) Conclusions: By promoting parent-child intimacy and connectedness to nature, and by utilizing the chain mediating effects of both, mindful parenting positively impacted children's creative tendencies.

Achieving high selectivity and activity of CO2 electroreduction to formate by in-situ synthesis of single atom Pb doped Cu catalysts.

Exploring highly selective and stable electrocatalysts is of great significance for the electrochemical conversion of CO2 into fuel. Herein, a three-dimensional (3D) nanostructure catalyst was developed by doping Pb single-atom (PbSA) in-situ on carbon paper (PbSA100-Cu/CP) through a low-energy and economical method. The designed catalyst exhibited abundant active sites and was beneficial to CO2 adsorption, activation, and subsequent conversion to fuel. Interestingly, PbSA100-Cu/CP showed a prominent Faraday efficiency (FE) of 97 % at -0.9 V versus reversible hydrogen electrode (vs. RHE) and a high partial current density of 27.9 mA·cm-2 for formate. Also, the catalyst remained significantly stable for 60 h during the durability test. The reaction mechanism was investigated by density functional theory (DFT), demonstrating that the doping PbSA induced the electrons redistribution, promoted the formate generation, reduced the rate-determining step (RDS) energy barrier, and inhibited the hydrogen evolution reaction. The study aims to provide a new strategy for developing of single-atom catalysts with high selectivity and stability, which will help reduce environmental pressure and alleviate energy problems.

Super-enhancer mediated upregulation of MYEOV suppresses ferroptosis in lung adenocarcinoma.

Super-enhancers (SEs) exerted a crucial role in regulating the transcription of oncogenes across various malignancies while the roles of SEs driven genes and the core regulatory elements remain elusive in LUAD. In this study, cancer-specific-SE-genes of lung adenocarcinoma (LUAD) were profiled through H3K27ac ChIP-seq data of cancer cell lines and normal lung tissues, which enriched in in biological processes and pathways integral to the pathophysiology of LUAD. Based on this study, LUAD cells were susceptible to SEs inhibitors, with a reduction of cell proliferation as well as an elevation of apoptosis upon JQ1 or THZ1 intervention. Moreover, the integration of SEs landscapes, CRISPRi, ChIP-PCR, Hi-C data analysis and dual-luciferase reporter assays revealed that myeloma overexpressed gene (MYEOV) was aberrantly overexpressed in LUAD via transcriptional activation by the core SE elements. Functionally, the knockdown of MYEOV undermined cell proliferation in vitro and tumor growth in vivo. In addition, the knockdown of MYEOV generated a prominent ferroptotic phenotype, characterized by elevation of intracellular ferrous iron, reactive oxygen species and lipid peroxidation, together with alteration in marker proteins (SLC7A11, GPX4, FTH1, and ACSL4). Instead, the overexpression of MYEOV accelerated cell proliferation and abrogated ferroptosis. Clinically, the overexpression of MYEOV was observed in LUAD tissues indicating a poor prognosis in patients with LUAD. Mechanistically, SMPD1-induced autophagic degradation of GPX4 assumed a crucial role in the process of ferroptosis triggered by MYEOV knockdown. Serving as an oncogene repressing ferroptosis, promoting proliferation as well as shortening survival in LUAD, SEs-mediated activation of MYEOV might distinguish as a promising therapeutic target.

Low expression of lysosome-related genes KCNE1, NPC2, and SFTPD promote cancer cell proliferation and tumor associated M2 macrophage polarization in lung adenocarcinoma.

Background: Recent research has shown that lysosomes play a critical role in the onset and progression of malignancy by regulating tumor cell death through several mechanisms. Nevertheless, the involvement of lysosome-associated genes (LSAGs) in lung adenocarcinoma (LUAD) is still not well understood. Methods: LSAGs were identified in malignant lung epithelial cells, as well as biologically and functionally annotated by the comprehensive integration of single-cell and bulk RNA-sequencing data. Prognostic characterization of LSAGs was established, of which the accuracy and reliability were assessed by one-way Cox and LASSO regression. Correlations between LSAG properties and immune cell infiltration, chemotherapy, and immunotherapy were analyzed by integrated omics data. Finally, we characterized the expression of three LSAGs (KCNE1, NPC2, and SFTPD) in malignant lung epithelium and assessed their impact on tumor malignancy related phenotypes. Results: We identified 18 LSAGs associated with prognosis, of which 3 LSAGs were used to construct prognostic models. High-risk patients had worse survival and the model predicted it better than other clinical indicators. Based on the functional enrichment analyses, LSAGs were associated with binding and molecular activity functions, inhibition of DNA damage repair and tumor growth, IL7 signaling pathway, and glycolysis. M0 macrophages and M1 macrophages were substantially enriched in high-risk patients. Conversely, there was a considerable enrichment of resting dendritic cells and M2 macrophages in patients at low risk. We also found that risk scores predicted the outcome of immunotherapy. In vitro, we found that KCNE1, NPC2, and SFTPD were lowly expressed in malignant epithelial cells and patients with low expression of KCNE1, NPC2, and SFTPD had a higher percentage of M2 macrophage infiltration. Overexpression of KCNE1, NPC2, and SFTPD suppressed the proliferation and invasion of malignant cells, and M0 macrophages remarkably reduced M2 macrophage polarization and cellular secretion of pro-tumor cytokines. Conclusions: We used three LASGs-KCNE1, NPC2, and SFTPD-to develop and validate a predictive signature for LUAD patients. Furthermore, we found that low expression of KCNE1, NPC2, and SFTPD promotes lung cancer cell proliferation and invasion and M2 macrophage polarization. Our study may provide fresh perspectives for customized immunotherapy.