Targeting protein condensation in cGAS-STING signaling pathway.

The cGAS-STING signaling pathway plays a pivotal role in sensing cytosolic DNA and initiating innate immune responses against various threats, with disruptions in this pathway being associated with numerous immune-related disorders. Therefore, precise regulation of the cGAS-STING signaling is crucial to ensure appropriate immune responses. Recent research, including ours, underscores the importance of protein condensation in driving the activation and maintenance of innate immune signaling within the cGAS-STING pathway. Consequently, targeting condensation processes in this pathway presents a promising approach for modulating the cGAS-STING signaling and potentially managing associated disorders. In this review, we provide an overview of recent studies elucidating the role and regulatory mechanism of protein condensation in the cGAS-STING signaling pathway while emphasizing its pathological implications. Additionally, we explore the potential of understanding and manipulating condensation dynamics to develop novel strategies for mitigating cGAS-STING-related disorders in the future.

Microbial fungicides can positively affect aubergine photosynthetic properties, soil enzyme activity and microbial community structure.

Background: This study examined the effects of microbial agents on the enzyme activity, microbial community construction and potential functions of inter-root soil of aubergine (Fragaria × ananassa Duch.). This study also sought to clarify the adaptability of inter-root microorganisms to environmental factors to provide a theoretical basis for the stability of the microbiology of inter-root soil of aubergine and for the ecological preservation of farmland soil. Methods: Eggplant inter-root soils treated with Bacillus subtilis (QZ_T1), Bacillus subtilis (QZ_T2), Bacillus amyloliquefaciens (QZ_T3), Verticillium thuringiensis (QZ_T4) and Verticillium purpureum (QZ_T5) were used to analyse the effects of different microbial agents on the inter-root soils of aubergine compared to the untreated control group (QZ_CK). The effects of different microbial agents on the characteristics and functions of inter-root soil microbial communities were analysed using 16S rRNA and ITS (internal transcribed spacer region) high-throughput sequencing techniques. Results: The bacterial diversity index and fungal diversity index of the aubergine inter-root soil increased significantly with the application of microbial fungicides; gas exchange parameters and soil enzyme activities also increased. The structural and functional composition of the bacterial and fungal communities in the aubergine inter-root soil changed after fungicide treatment compared to the control, with a decrease in the abundance of phytopathogenic fungi and an increase in the abundance of beneficial fungi in the soil. Enhancement of key community functions, reduction of pathogenic fungi, modulation of environmental factors and improved functional stability of microbial communities were important factors contributing to the microbial stability of fungicide-treated aubergine inter-root soils.

Comprehensive identification and expression analysis of FAR1/FHY3 genes under drought stress in maize (Zea mays L.).

Background: FAR1/FHY3 transcription factors are derived from transposase, which play important roles in light signal transduction, growth and development, and response to stress by regulating downstream gene expression. Although many FAR1/FHY3 members have been identified in various species, the FAR1/FHY3 genes in maize are not well characterized and their function in drought are unknown. Method: The FAR1/FHY3 family in the maize genome was identified using PlantTFDB, Pfam, Smart, and NCBI-CDD websites. In order to investigate the evolution and functions of FAR1 genes in maize, the information of protein sequences, chromosome localization, subcellular localization, conserved motifs, evolutionary relationships and tissue expression patterns were analyzed by bioinformatics, and the expression patterns under drought stress were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of 24 ZmFAR members in maize genome, which can be divided into five subfamilies, with large differences in protein and gene structures among subfamilies. The promoter regions of ZmFARs contain abundant abiotic stress-responsive and hormone-respovensive cis-elements. Among them, drought-responsive cis-elements are quite abundant. ZmFARs were expressed in all tissues detected, but the expression level varies widely. The expression of ZmFARs were mostly down-regulated in primary roots, seminal roots, lateral roots, and mesocotyls under water deficit. Most ZmFARs were down-regulated in root after PEG-simulated drought stress. Conclusions: We performed a genome-wide and systematic identification of FAR1/FHY3 genes in maize. And most ZmFARs were down-regulated in root after drought stress. These results indicate that FAR1/FHY3 transcription factors have important roles in drought stress response, which can lay a foundation for further analysis of the functions of ZmFARs in response to drought stress.

Chiral Jahn-Teller Distortion in Quasi-Planar Boron Clusters.

In this work, we have observed that some chiral boron clusters (B16-, B20-, B24-, and B28-) can simultaneously have helical molecular orbitals and helical spin densities; these seem to be the first compounds discovered to have this intriguing property. We show that chiral Jahn-Teller distortion of quasi-planar boron clusters drives the formation of the helical molecular spin densities in these clusters and show that elongation/enhancement in helical molecular orbitals can be achieved by simply adding more building blocks via a linker. Aromaticity of these boron clusters is discussed. Chiral boron clusters may find potential applications in spintronics, such as molecular magnets.

Fragment-Based Deep Learning for Simultaneous Prediction of Polarizabilities and NMR Shieldings of Macromolecules and Their Aggregates.

Simultaneous prediction of the molecular response properties, such as polarizability and the NMR shielding constant, at a low computational cost is an unresolved issue. We propose to combine a linear-scaling generalized energy-based fragmentation (GEBF) method and deep learning (DL) with both molecular and atomic information-theoretic approach (ITA) quantities as effective descriptors. In GEBF, the total molecular polarizability can be assembled as a linear combination of the corresponding quantities calculated from a set of small embedded subsystems in GEBF. In the new GEBF-DL(ITA) protocol, one can predict subsystem polarizabilities based on the corresponding molecular wave function (thus electron density and ITA quantities) and DL model rather than calculate them from the computationally intensive coupled-perturbed Hartree-Fock or Kohn-Sham equations and finally obtain the total molecular polarizability via a linear combination equation. As a proof-of-concept application, we predict the molecular polarizabilities of large proteins and protein aggregates. GEBF-DL(ITA) is shown to be as accurate enough as GEBF, with mean absolute percentage error <1%. For the largest protein aggregate (>4000 atoms), GEBF-DL(ITA) gains a speedup ratio of 3 compared with GEBF. It is anticipated that when more advanced electronic structure methods are used, this advantage will be more appealing. Moreover, one can also predict the NMR chemical shieldings of proteins with reasonably good accuracy. Overall, the cost-efficient GEBF-DL(ITA) protocol should be a robust theoretical tool for simultaneously predicting polarizabilities and NMR shieldings of large systems.

Some Recent Advances in Density-Based Reactivity Theory.

Establishing a chemical reactivity theory in density functional theory (DFT) language has been our intense research interest in the past two decades, exemplified by the determination of steric effect and stereoselectivity, evaluation of electrophilicity and nucleophilicity, identification of strong and weak interactions, and formulation of cooperativity, frustration, and principle of chirality hierarchy. In this Featured Article, we first overview the four density-based frameworks in DFT to appreciate chemical understanding, including conceptual DFT, use of density associated quantities, information-theoretic approach, and orbital-free DFT, and then present a few recent advances of these frameworks as well as new applications from our studies. To that end, we will introduce the relationship among these frameworks, determining the entire spectrum of interactions with Pauli energy derivatives, performing topological analyses with information-theoretic quantities, and extending the density-based frameworks to excited states. Applications to examine physiochemical properties in external electric fields and to evaluate polarizability for proteins and crystals are discussed. A few possible directions for future development are followed, with the special emphasis on its merger with machine learning.

A Phase 1b Clinical Trial of Neoadjuvant Radio-immunotherapy for Esophageal Squamous Cell Cancer.

PURPOSE: Neoadjuvant chemoradiotherapy is the recommended treatment for patients with resectable esophageal cancer but is associated with a higher incidence of adverse effects. Given the efficacy of immunotherapy, we propose a chemotherapy-free regimen of neoadjuvant radio-immunotherapy (NRIT) to balance therapeutic efficacy and potential side effects or overtreatment. METHODS AND MATERIALS: In this phase 1b clinical trial, we assessed the safety and efficacy of NRIT in esophageal squamous cell cancer. The enrolled patients received 41.4 Gy of radiation and 4 cycles of 240 mg of toripalimab injection before surgery. The primary endpoint was treatment-related adverse events and the secondary endpoints were pathologic complete response and major pathologic response. Immunohistochemistry and multiplex immunofluorescence staining were used to evaluate the tumor microenvironment before and after neoadjuvant treatment. RESULTS: Of the 22 patients enrolled, 19 underwent R0 surgery. One patient discontinued neoadjuvant immune therapy due to experiencing a grade 3 treatment-related adverse event. Three patients did not undergo surgery due to tumor progression or side effects. Among the patients who underwent surgery, 3 patients experienced serious complications shortly after surgery. Upon pathologic evaluation, the pathologic complete response and major pathologic response rates were 47.4% and 68.4%, respectively. CONCLUSIONS: The NRIT regimen is safe and feasible for patients with esophageal squamous cell cancer.

Simultaneous identification of strong and weak interactions with Pauli energy, Pauli potential, Pauli force, and Pauli charge.

Strong and weak interatomic interactions in chemical and biological systems are ubiquitous, yet how to identify them on a unified theoretical foundation is still not well established. Recently, we proposed employing Pauli energy-based indexes, such as strong covalent interaction and bonding and noncovalent interaction indexes, in the framework of density functional theory for the purpose. In this work, we extend our previous theoretical work by directly employing Pauli energy, Pauli potential, Pauli force, and Pauli charge to simultaneously identify both strong covalent bonding and weak noncovalent interactions. Our results from this work elucidate that using their signature isosurfaces, we can identify different types of interactions, either strong or weak, including single, double, triple, and quadruple covalent bonds, ionic bond, metallic bond, hydrogen bonding, and van der Waals interaction. We also discovered strong linear correlations between Pauli energy derived quantities and different covalent bond orders. These qualitative and quantitative results from our present study solidify the viewpoint that a unified approach to simultaneously identify both strong and weak interactions is possible. In our view, this work signifies one step forward towards the goal of establishing a density-based theory of chemical reactivity in density functional theory.

Directionality and additivity effects of molecular acidity and aromaticity for substituted benzoic acids under external electric fields.

Our recent study [M. Li et al.Phys. Chem. Chem. Phys., 2023, 25, 2595-2605] unveiled that the impact of an external electric field on molecular acidity and aromaticity for benzoic acid is directional, which can be understood using changes in frontier orbitals and partial charges. However, it is unclear if the effect will disappear when substituting groups are present and whether new patterns of changes will show up. In this work, as a continuation of our efforts to appreciate the impact of external electric fields on physiochemical properties, we find that the directionality effect is still in place for substituted benzoic acid derivatives and that there exists the additivity effect with respect to the number of substituent groups, regardless of the direction of the applied field and the type of substituting groups. We confirm the findings using electron-donating and electron-accepting groups with the electric field applied either parallelly or perpendicularly to the carboxyl group along the benzene ring. The directionality and additivity effects uncovered from this work should enrich the body of our knowledge about the impact of external electric fields on physiochemical properties and could be applicable to other systems and properties as well.

Accurate and Efficient Prediction of Post-Hartree-Fock Polarizabilities of Condensed-Phase Systems.

To accurately and efficiently predict the molecular response properties (such as polarizability) at post-Hartree-Fock levels for condensed-phase systems under periodic boundary conditions (PBC) is still an unaccomplished and ongoing task. We demonstrate that static isotropic polarizabilities can be cost-effectively predicted at post-Hartree-Fock levels by combining the linear-scaling generalized energy-based fragmentation (GEBF) and information-theoretic approach (ITA) quantities. In PBC-GEBF, the total molecular polarizability of an extended system is obtained as a linear combination of the corresponding quantities of a series of small embedded subsystems of several monomers. Here, we show that in the PBC-GEBF-ITA framework, one can obtain the molecular polarizabilities and establish linear relations to ITA quantities. Once these relations are established for smaller subsystems, one can predict the polarizabilities of larger subsystems directly from the molecular wavefunction (or electron density) via ITA quantities. Alternatively, one can determine the total molecular polarizability via a linear combination equation in PBC-GEBF. We have corroborated that this newly proposed PBC-GEBF-ITA protocol is much more efficient than the original PBC-GEBF approach but is not much less accurate and that this conclusion holds for both many-body perturbation theory and the coupled cluster calculations. Good efficiency and transferability of the PBC-GEBF-ITA protocol are demonstrated for periodic systems with several hundred atoms in a unit cell.

Identification and analysis of differentially expressed trihelix genes in maize (Zea mays) under abiotic stresses.

Background: Trihelix transcription factors play important roles in triggering plant growth and imparting tolerance against biotic and abiotic stresses. However, a systematical analysis of the trihelix transcription factor family under heat and drought stresses in maize has not been reported. Methods: PlantTFDB and TBtools were employed to identify the trihelix domain-containing genes in the maize genome. The heat-regulated transcriptome data for maize were obtained from NCBI to screen differentially expressed ZmTHs genes through statistical analysis. The basic protein sequences, chromosomal localization, and subcellular localization were analyzed using Maize GDB, Expasy, SOMPA, TBtools, and Plant-mPLoc. The conserved motifs, evolutionary relationships, and cis-elements, were analyzed by MEME, MEGA7.0 and PlantCARE software, respectively. The tissue expression patterns of ZmTHs and their expression profiles under heat and drought stress were detected using quantitative real-time PCR (qRT-PCR). Results: A total of 44 trihelix family members were discovered, and members were distributed over 10 chromosomes in the maize genome. A total of 11 genes were identified that were regulated by heat stress; these were unevenly distributed on chromosomes 1, 2, 4, 5, and 10. ZmTHs encoded a total of 16 proteins, all of which were located in the nucleus; however, ZmTH04.1 was also distributed in the chloroplast. The protein length varied from 206 to 725 amino acids; the molecular weight ranged from 22.63 to 76.40 kD; and the theoretical isoelectric point (pI) ranged from 5.24 to 11.2. The protein's secondary structures were mainly found to be random coils and α-helices, with fewer instances of elongation chains and ß-rotations. Phylogenetic relationship analysis showed that these can be divided into five sub-groups. The conserved domain of ZmTHs was GT1 or MyB_DNA-Bind_4. The protein and gene structure of ZmTHs differed greatly among the subfamilies, while the structures within the subfamilies were similar. The promoter of ZmTHs contained abundant tissue-specific expression cis-acting elements and abiotic stress response elements. qRT-PCR analysis showed that ZmTHs expression levels were significantly different in different tissues. Furthermore, the expression of ZmTH08 was dramatically up-regulated by heat stress, while the expression of ZmTH03, ZmTH04, ZmTH05, ZmTH06, ZmTH07, ZmTH09, ZmTH10, and ZmTH11 were down-regulated by heat stress. Upon PEG-simulated drought stress, ZmTH06 was significantly up-regulated, while ZmTH01 and ZmTH07 were down-regulated. Conclusions: We performed a genome-wide, systematic identification and analysis of differentially expressed trihelix genes under heat and drought stresses in maize.

Excited-State Polarizabilities: A Combined Density Functional Theory and Information-Theoretic Approach Study.

Accurate and efficient determination of excited-state polarizabilities (α) is an open problem both experimentally and computationally. Following our previous work, (Phys. Chem. Chem. Phys. 2023, 25, 2131-2141), in which we employed simple ground-state (S0) density-related functions from the information-theoretic approach (ITA) to accurately and efficiently evaluate the macromolecular polarizabilities, in this work we aimed to predict the lowest excited-state (S1) polarizabilities. The philosophy is to use density-based functions to depict excited-state polarizabilities. As a proof-of-principle application, employing 2-(2'-hydroxyphenyl)benzimidazole (HBI), its substituents, and some other commonly used ESIPT (excited-state intramolecular proton transfer) fluorophores as model systems, we verified that either with S0 or S1 densities as an input, ITA quantities can be strongly correlated with the excited-state polarizabilities. When transition densities are considered, both S0 and S1 polarizabilities are in good relationships with some ITA quantities. The transferability of the linear regression model is further verified for a series of molecules with little or no similarity to those molecules in the training set. Furthermore, the excitation energies can be predicted based on multivariant linear regression equations of ITA quantities. This study also found that the nature of both the ground-state and excited-state polarizabilities of these species are due to the spatial delocalization of the electron density.

Efficient and accurate density-based prediction of macromolecular polarizabilities.

Accurately and efficiently predicting macromolecules' polarizabilities is an open problem. In this work, we employ a few simple density-based quantities from the information-theoretic approach (ITA) to predict polarizability of proteins. We first build quantitative structure/property relationships between molecular polarizabilities and ITA quantities. We then verify the broad applicability of ITA quantities for polarizability prediction for inorganic, organic, and biological systems with both localized and delocalized electronic structure. As a proof-of-concept application, we predict the molecular polarizabilities of complex proteins. Based on the linear regression equations for 20 natural amino acid residues, 400 dipeptides, and 8000 tripeptides, one then predicts the molecular polarizability of a larger peptide or even a protein once the molecular wavefunction is obtained. Because it is extremely costly to determine the wavefunction for a macromolecule like a protein, we propose to combine the ITA with the linear-scaling generalized energy-based fragmentation (GEBF) method to predict the macromolecular polarizability. In GEBF, the total molecular polarizability is obtained as a linear combination of the corresponding quantities from a series of small subsystems. We can predict them based on the subsystem wavefunction and linear regression equations rather than compute them from the nearly-intractable coupled-perturbed Hartree-Fock or Kohn-Sham equations for the whole macromolecule. Computational results showcase that the GEBF-ITA protocol should be an inexpensive yet accurate theoretical tool for predicting macromolecular polarizabilities.

Biocompatible carboxymethyl cellulose-based super-elastic hierarchical sponge via a novel templating and plasticizing method.

Herein, a facile method to fabricate hierarchical super-elastic (SE) sponge using a water-soluble cellulose derivative, carboxymethyl cellulose (CMC), is reported. The method includes ice templating and porogen leaching steps which facilitate to generate macro-sized pores as well as pore wall structures that can dissipate stress effectively. By controlling the porogen content, the specific surface area and the morphology of the sponges can be tuned. Furthermore, a plasticizing method was used before vacuum drying to reduce the deformation of the inner structure. The derived hierarchical SE CMC sponges exhibit excellent fatigue resistance, fast shape recovery, high-water absorption, biosafeness, and fast degradation. Thus, our strategy provides a novel method for the construction of SE sponges which show great potential in green elastic wound dressing, tissue engineering, and absorbent materials.

SES1 is vital for seedling establishment and post-germination growth under high-potassium stress conditions in Arabidopsis thaliana.

Background: The potassium ion (K+) plays an important role in maintaining plant growth and development, while excess potassium in the soil can cause stress to plants. The understanding of the molecular mechanism of plant's response to high KCl stress is still limited. Methods: At the seed stage, wild type (WT) and SENSITIVE TO SALT1 (SES1) mutants were exposed to different concentrations of potassium treatments. Tolerance was assayed as we compared their performances under stress using seedling establishment rate and root length. Na+content, K+content, and K+/Na+ ratio were determined using a flame atomic absorption spectrometer. In addition, the expressions of KCl-responding genes and ER stress-related genes were also detected and analyzed using qRT-PCR. Results: SES1 mutants exhibited seedling establishment defects under high potassium concentration conditions and exogenous calcium partially restored the hypersensitivity phenotype of ses1 mutants. The expression of some K+ transporter/channel genes were higher in ses1-2, and the ratio of potassium to sodium (K+/Na+) in ses1-2 roots decreased after KCl treatment compared with WT. Further analysis showed that the ER stress marker genes were dramatically induced by high K+ treatment and much higher expression levels were detected in ses1-2, indicating ses1-2 suffers a more serious ER stress than WT, and ER stress may influence the seedling establishment of ses1-2 under high KCl conditions. Conclusion: These results strongly indicate that SES1 is a potassium tolerance relevant molecule that may be related to maintaining the seedling K+/Na+ balance under high potassium conditions during seedling establishment and post-germination growth. Our results will provide a basis for further studies on the biological roles of SES1 in modulating potassium uptake, transport, and adaptation to stress conditions.

Development and Applications of the Density-Based Theory of Chemical Reactivity.

Density functional theory, which is well-recognized for its accuracy and efficiency, has become the workhorse for modeling the electronic structure of molecules and extended materials in recent decades. Nevertheless, establishing a density-based conceptual framework to appreciate bonding, stability, function, reactivity, and other physicochemical properties is still an unaccomplished task. In this Perspective, we at first provide an overview of the four pathways currently available in the literature to tackle the matter, including orbital-free density functional theory, conceptual density functional theory, direct use of density-associated quantities, and the information-theoretic approach. Then, we highlight several recent advances of employing these approaches to realize new understandings for chemical concepts such as covalent bonding, noncovalent interactions, cooperation, frustration, homochirality, chirality hierarchy, electrophilicity, nucleophilicity, regioselectivity, and stereoselectivity. Finally, we provide a few possibilities for the future development of this relatively uncharted territory. Opportunities are abundant, and they are all ours for the taking.

A Density Functional Theory and Information-Theoretic Approach Study of Interaction Energy and Polarizability for Base Pairs and Peptides.

Using density functional theory (DFT) and the information-theoretic approach (ITA) quantities to appreciate the energetics and properties of biopolymers is still an unaccomplished and ongoing task. To this end, we studied the building blocks of nucleic acid base pairs and small peptides. For base pairs, we have dissected the relative importance of energetic components by using two energy partition schemes in DFT. Our results convincingly show that the exchange-correlation effect predominantly governs the molecular stability of base pairs while the electrostatic potential plays a minor but indispensable role, and the steric effect is trivial. Furthermore, we have revealed that simple density-based ITA functions are in good relationships with molecular polarizabilities for a series of 30 hydrogen-bonded base pairs and all 20 natural α-amino acids, 400 dipeptides, and 8000 tripeptides. Based on these lines, one can easily predict the molecular polarizabilities of larger peptides, even proteins as long as the total molecular wavefunction is available, rather than solving the computationally demanding coupled-perturbed Hartree-Fock (CPHF) equation or its DFT counterpart coupled-perturbed Kohn-Sham (CPKS) equation.

Bone marrow-derived mesenchymal stem cells ameliorate severe acute pancreatitis by inhibiting oxidative stress in rats.

To investigate whether bone marrow mesenchymal stem cells (BMSCs) attenuate pancreatic injury via mediating oxidative stress in severe acute pancreatitis (SAP). The SAP model was established in rats. Phosphate buffered saline (PBS) or BMSCs were injected into the rats by tail veins. ML385 was used to down-regulate Nrf2 expression in rats. Pancreatic pathological score was used to evaluated pancreatic injury. Inflammatory-associated cytokines, serum lipase and amylase, levels of myeloperoxidase, malondialdehyde, reactive oxygen species and superoxide dismutase, as well as catalase activity were measured for injury severity evaluation. ML385 aggravates oxidative stress in SAP + ML385 group, compared with SAP + PBS group. BMSCs transplantation alleviated pancreatic injury and enhance antioxidant tolerance in SAP + BMSCs group, while ML385 administration weakened this efficacy in SAP + BMSCs + ML385 group. In addition, BMSCs promoted Nrf2 nuclear translocation via PI3K/AKT signaling pathway. Besides, BMSCs reduced inflammatory response by inhibiting NF-κB signaling pathway in SAP. BMSCs can inhibit oxidative stress and reduce pancreatic injury via inducing Nrf2 nuclear translocation in SAP.

Revisiting the trapping of noble gases (He-Kr) by the triatomic H3+ and Li3+ species: a density functional reactivity theory study.

Small atomic clusters with exotic stability, bonding, aromaticity, and reactivity properties can be made use of for various purposes. In this work, we revisit the trapping of noble gas atoms (He-Kr) by the triatomic H3+ and Li3+ species by using some analytical tools from density functional theory, conceptual density functional theory, and the information-theoretic approach. Our results showcase that though similar in geometry, H3+ and Li3+ exhibit markedly different behavior in bonding, aromaticity, and reactivity properties after the addition of noble gas atoms. Moreover, the exchange-correlation interaction and steric effect are key energy components in stabilizing the clusters. This study also finds that the origin of the molecular stability of these species is due to the spatial delocalization of the electron density distribution. Our work provides an additional arsenal towards a better understanding of small atomic clusters capturing noble gases.

The Effect of Extracellular Superoxide Dismutase (SOD3) Gene in Lung Cancer.

Background: The recognition of new diagnostic and prognostic biological markers for lung cancer, the most severe malignant tumor, is an essential and eager study. In a microenvironment, superoxide dismutase 3 (SOD3) can adjust active oxygen, and it refers to a secreted antioxidant enzyme. It was also found to be cancer-related, and in lung cancer, it was remarkably down-regulated. More and more new cancer research focuses on the function of SOD3. Despite this, there is no good description of SOD3 function in the LC progression. Methods: Through bioinformatics analysis, we found that SOD3 was a possible novel lung cancer gene in this study. We analyzed data sets from Gene Expression Comprehensive Database (GEO) and the Cancer Genome Atlas (TCGA), and SOD3 expression was studied in lung cancer. This study estimated the SOD3 diagnosis and prognosis through gene expression differential display, gene set enrichment analysis (GSEA), enrichment and genomes (KEGG) analysis, and gene ontology (GO). Then in order to investigate the SOD3 presentation in lung cancer cells, we used Western Blot and also applied Flow cytometry to detect the impact of anti-tumor medicine on tumor cell apoptosis. Results: We found that the expression level of SOD3 in lung cancer was low (P = 4.218E-29), while the survival of lung cancer patients with high SOD3 expression was shorter (LUSC p =0.00086, LUAD p=0.00038). According to the result of western blot, the expression of SOD3 in tumor cells was higher than that in normal cells. The ratio of early apoptosis induced by anti-cancer drugs was 10.5% in normal cells, 35.1% in squamous cell carcinoma and 36.9% in adenocarcinoma.The SOD3 high expression was associated with poor survival probability by multivariate analysis (HR: 1.006, 95% CI 1.002-1.011, p=0.006). Moreover, SOD3 high expression group had higher ESTIMATE scores, and larger amount of immune infiltrating cells. SOD3 expression is correlated with PDCD1 and CTLA4 expression. Conclusions: SOD3 gene can be used as a prognostic gene in lung cancer patients, and lung cancer patients with high expression of this gene can reap worse prognostic outcome. It can be used as a new clinical method and prognosticator for lung cancer patients.