Molecular adaptations underlying high-frequency hearing in the brain of CF bats species.

BACKGROUND: The majority of bat species have developed remarkable echolocation ability, especially for the laryngeally echolocating bats along with high-frequency hearing. Adaptive evolution has been widely detected for the cochleae in the laryngeally echolocating bats, however, limited understanding for the brain which is the central to echolocation signal processing in the auditory perception system, the laryngeally echolocating bats brain may also undergo adaptive changes. RESULT: In order to uncover the molecular adaptations related with high-frequency hearing in the brain of laryngeally echolocating bats, the genes expressed in the brain of Rhinolophus ferrumequinum (CF bat) and Myotis pilosus (FM bat) were both detected and also compared. A total of 346,891 genes were detected and the signal transduction mechanisms were annotated by the most abundant genes, followed by the transcription. In hence, there were 3,088 DEGs were found between the two bat brains, with 1,426 highly expressed in the brain of R. ferrumequinum, which were significantly enriched in the neuron and neurodevelopmental processes. Moreover, we found a key candidate hearing gene, ADCY1, playing an important role in the R. ferrumequinum brain and undergoing adaptive evolution in CF bats. CONCLUSIONS: Our study provides a new insight to the molecular bases of high-frequency hearing in two laryngeally echolocating bats brain and revealed different nervous system activities during auditory perception in the brain of CF bats.

Stripe rust effector Pst21674 compromises wheat resistance by targeting transcription factor TaASR3.

Pathogens compromise host defense responses by strategically secreting effector proteins. However, the molecular mechanisms by which effectors manipulate disease-resistance factors to evade host surveillance remain poorly understood. In this study, we characterized a Puccinia striiformis f. sp. tritici (Pst) effector Pst21674 with a signal peptide. Pst21674 was significantly upregulated during Pst infections in wheat (Triticum aestivum L.) and knocking down Pst21674 by host-induced gene silencing led to reduced Pst pathogenicity and restricted hyphal spread in wheat. Pst21674 interaction with the abscisic acid-, stress-, and ripening-induced protein TaASR3 was validated mainly in the nucleus. Size exclusion chromatography, bimolecular fluorescence complementation, and luciferase complementation imaging assays confirmed that TaASR3 could form a functional tetramer. Virus-induced gene silencing and overexpression demonstrated that TaASR3 contributes to wheat resistance to stripe rust by promoting accumulation of reactive oxygen species and cell death. Additionally, transcriptome analysis revealed that the expression of defense-related genes was regulated in transgenic wheat plants overexpressing TaASR3. Interaction between Pst21674 and TaASR3 interfered with the polymerization of TaASR3 and suppressed TaASR3-mediated transcriptional activation of defense-related genes. These results indicate that Pst21674 serves as an important virulence factor secreted into the host nucleus to impede wheat resistance to Pst, possibly by targeting and preventing polymerization of TaASR3.

Polyacetylene-Based Asymmetric Bicyclic Polymer by Blocking-Cyclization Technique.

A rare asymmetric bicyclic polymer containing different length of conjugated polyacetylene segments is synthesized by metathesis cyclopolymerization-mediated blocking-cyclization technique. The size of each single ring differs from each other, and the unique cyclic polymer topology is controlled by adjusting the feed ratio of monofunctional monomer to catalyst. The topological difference between linear and bicyclic polymers is confirmed by several techniques, and the visualized morphology of asymmetric bicyclic polymer is directly observed without tedious post-modification process. The photoelectric and thermal properties of polymers are investigated. This work expands the pathway for the derivation of cyclic polymers, and such unique topological structure enriches the diversity of cyclic polymer classes.

Protective effects of sulforaphane on inflammation, oxidative stress and intestinal dysbacteriosis induced by triphenyltin in Cyprinus carpio haematopterus.

The purpose of this experiment was to study the mitigation effect of sulforaphane (SFN) on fish toxicological damage caused by triphenyltin (TPT) pollution. A total of 320 healthy fish (56.9 ± 0.4g) were randomly placed into four groups, each with four duplicates. The control group was fed the basal diet, the TPT group was exposed to 10 ng/L TPT on the basis of the control group, the SFN group was fed a diet supplemented with 10 mg/kg SFN, the SFN + TPT group was exposed to 10 ng/L TPT on the basis of the SFN group. Each tank had 20 fish and the breeding lasted for 8 weeks. The present study found that the antioxidant enzyme activity in the TPT group was significantly lower than that of the control group (P < 0.05). In addition, compared with the control group, the mRNA expression of pro-inflammatory factors (IL-6, TNF-α) were significantly induced, and the anti-inflammatory factor genes (IL-10, TGF) were significantly inhibited (P < 0.05) in TPT group. SFN relieved the changes of inflammatory factors caused by TPT, ameliorated oxidative stress, improved antioxidant enzyme (include SOD, CAT, GSH, GPx) activities (P < 0.05). 16s RNA analysis indicated that exposure to TPT caused changes in intestinal microflora. The results of the study showed that after exposure to TPT, some beneficial genera of bacteria in the gut of Rhizobiaceae, Bdellovibrio and Candidatus Alysiosphaera were decreased. The bacteria associated with intestinal inflammation including Propionibacterium, Rubrobacter, Anaerorhabdus_furcosa_group, Rikenellaceae and Eubacterium_brachy were upregulated. However, the SFN treatment group significantly down-regulated the above five inflammation-related bacteria. The above results indicated that TPT caused oxidative stress and inflammation in fish intestines, changed the intestinal microflora, and dietary SFN could improve antioxidant status, regulate inflammation and intestinal health. Therefore, SFN is a promising diet additive for improving fish damage caused by TPT contamination.

Full-Length Transcriptome of the Great Himalayan Leaf-Nosed Bats (Hipposideros armiger) Optimized Genome Annotation and Revealed the Expression of Novel Genes.

The Great Himalayan Leaf-nosed bat (Hipposideros armiger) is one of the most representative species of all echolocating bats and is an ideal model for studying the echolocation system of bats. An incomplete reference genome and limited availability of full-length cDNAs have hindered the identification of alternatively spliced transcripts, which slowed down related basic studies on bats' echolocation and evolution. In this study, we analyzed five organs from H. armiger for the first time using PacBio single-molecule real-time sequencing (SMRT). There were 120 GB of subreads generated, including 1,472,058 full-length non-chimeric (FLNC) sequences. A total of 34,611 alternative splicing (AS) events and 66,010 Alternative Polyadenylation (APA) sites were detected by transcriptome structural analysis. Moreover, a total of 110,611 isoforms were identified, consisting of 52% new isoforms of known genes and 5% of novel gene loci, as well as 2112 novel genes that have not been annotated before in the current reference genome of H. armiger. Furthermore, several key novel genes, including Pol, RAS, NFKB1, and CAMK4, were identified as being associated with nervous, signal transduction, and immune system processes, which may be involved in regulating the auditory nervous perception and immune system that helps bats to regulate in echolocation. In conclusion, the full-length transcriptome results optimized and replenished existing H. armiger genome annotation in multiple ways and offer advantages for newly discovered or previously unrecognized protein-coding genes and isoforms, which can be used as a reference resource.

Unveiling characteristics and determinants of China's wind power geographies towards low-carbon transition.

The temporal and spatial patterns of wind power installation and the evaluation of carbon emission reduction potentials are of great significance to promoting China's wind power development planning and dual carbon targets achievement. This study analyzes the temporal and spatial characteristics, identifies main driving factors, and measures carbon emission reduction potentials of China's wind power installation by province based on spatial autocorrelation analysis and spatial econometric model. Overall, China's wind power installed capacity increased rapidly from 346 MW in 2000 to 279,550 MW in 2020, basically showing a significant positive spatial correlation during 2000 and 2020. Regarding driving factors of wind power installation, the technological factors and environmental factors were the main positive factors for wind power installation, and the economic factors and resource endowments showed positive spatial spillover effects. Regarding carbon emission reduction potentials, the carbon emission reduction potentials of China's wind power installation increased by year, among which Northwest China gradually accelerated Northeast China after 2015. Based on China's wind power evolution characteristics and carbon emission reduction potentials, this study attempts to provide quantitative supports and policy implications to promote sustainable development of wind power industry and the achievement of carbon peak and carbon neutrality within China.

Full-Length Transcriptome of Myotis pilosus as a Reference Resource and Mining of Auditory and Immune Related Genes.

Rickett's big-footed bat, Myotis pilosus, which belongs to the family Vespertilionida, is the only known piscivorous bat in East Asia. Accurate whole genome and transcriptome annotations are essential for the study of bat biological evolution. The lack of a whole genome for M. pilosus has limited our understanding of the molecular mechanisms underlying the species' evolution, echolocation, and immune response. In the present work, we sequenced the entire transcriptome using error-corrected PacBio single-molecule real-time (SMRT) data. Then, a total of 40 GB of subreads were generated, including 29,991 full-length non-chimeric (FLNC) sequences. After correction by Illumina short reads and de-redundancy, we obtained 26,717 error-corrected isoforms with an average length of 3018.91 bp and an N50 length of 3447 bp. A total of 1528 alternative splicing (AS) events were detected by transcriptome structural analysis. Furthermore, 1032 putative transcription factors (TFs) were identified, with additional identification of several long non-coding RNAs (lncRNAs) with high confidence. Moreover, several key genes, including PRL-2, DPP4, Glul, and ND1 were also identified as being associated with metabolism, immunity, nervous system processes, and auditory perception. A multitude of pattern recognition receptors was identified, including NLR, RLR, SRCR, the antiviral molecule IRF3, and the IFN receptor subunit IFNAR1. High-quality reference genomes at the transcriptome level may be used to quantify gene or transcript expression, evaluate alternative splicing levels, identify novel transcripts, and enhance genome annotation in bats.

Bioinformatics and expression analysis of histone modification genes in grapevine predict their involvement in seed development, powdery mildew resistance, and hormonal signaling.

BACKGROUND: Histone modification genes (HMs) play potential roles in plant growth and development via influencing gene expression and chromatin structure. However, limited information is available about HMs genes in grapes (Vitis vinifera L.). RESULTS: Here, we described detailed genome-wide identification of HMs gene families in grapevine. We identified 117 HMs genes in grapevine and classified these genes into 11 subfamilies based on conserved domains and phylogenetic relationships with Arabidopsis. We described the genes in terms of their chromosomal locations and exon-intron distribution. Further, we investigated the evolutionary history, gene ontology (GO) analysis, and syntenic relationships between grapes and Arabidopsis. According to results 21% HMs genes are the result of duplication (tandem and segmental) events and all the duplicated genes have negative mode of selection. GO analysis predicted the presence of HMs proteins in cytoplasm, nucleus, and intracellular organelles. According to seed development expression profiling, many HMs grapevine genes were differentially expressed in seeded and seedless cultivars, suggesting their roles in seed development. Moreover, we checked the response of HMs genes against powdery mildew infection at different time points. Results have suggested the involvement of some genes in disease resistance regulation mechanism. Furthermore, the expression profiles of HMs genes were analyzed in response to different plant hormones (Abscisic acid, Jasmonic acid, Salicylic acid, and Ethylene) at different time points. All of the genes showed differential expression against one or more hormones. CONCLUSION: VvHMs genes might have potential roles in grapevine including seed development, disease resistance, and hormonal signaling pathways. Our study provides first detailed genome-wide identification and expression profiling of HMs genes in grapevine.

Mode-locked Er-doped fiber laser based on PbS/CdS core/shell quantum dots as saturable absorber.

Previously, PbS/CdS core/shell quantum dots with excellent optical properties have been widely used as light-harvesting materials in solar cell and biomarkers in bio-medicine. However, the nonlinear absorption characteristics of PbS/CdS core/shell quantum dots have been rarely investigated. In this work, PbS/CdS core/shell quantum dots were successfully employed as nonlinear saturable absorber (SA) for demonstrating a mode-locked Er-doped fiber laser. Based on a film-type SA, which was prepared by incorporating the quantum dots with the polyvinyl alcohol (PVA), mode-locked Er-doped operation with a pulse width of 54 ps and a maximum average output power of 2.71 mW at the repetition rate of 3.302 MHz was obtained. Our long-time stable results indicate that the CdS shell can effectively protect the PbS core from the effect of photo-oxidation and PbS/CdS core/shell quantum dots were efficient SA candidates for demonstrating pulse fiber lasers due to its tunable absorption peak and excellent saturable absorption properties.

Photoregulating of Stretchability and Toughness of a Self-Healable Polymer Hydrogel.

Supramolecular hydrogels that are assembled through dynamic host-guest interactions have presented apparent potential in the construction of materials with promising performance. Herein, a photoregulated hydrogel cross-linked by host-guest interactions with multifunctions of high stretchability, strong toughness, and rapid self-healing property is reported. The hydrogel exhibits unique light-responsive property due to the introduction of two photoisomerized groups. For example, the stress-strain curve of the original hydrogel indicates 1020% rupture strain with the maximum tensile strain value of 214 kPa. Upon 365 nm light irradiation for an hour, its tensile strain increases to 15 times with lower tensile stress indicating a better stretchability. Moreover, the hydrogel is photochromic and surface patternable, where it can reversibly switch color between luminous yellow and brown while exposed to 365 and 440 nm light irradiation. It holds great promise for applying in self-recovering optically controlled and labeled elastic mechanical materials.

Responsiveness and Morphology Study of Dual Stimuli-Controlled Supramolecular Polymer.

The synthesis and characterization of a linear supramolecular polymer formed by dual host-guest recognitions is presented. The polymer linked by the orthogonal interactions of azobenzene with ß-cyclodextrin and methyl viologen with sulfonatocalix[4]arene is constructed, and the morphology change along with the formation and vanishment of host-guest interaction is investigated. The reversible disassembly-reassembly of the polymer induced by light and the redox process are monitored by UV-vis and cyclic voltammetry, respectively. The interesting morphology differences between the monomer guest (G), supramolecular polymer (P), and light dissembled product pseudorotaxane (D1) are observed and analyzed. G conducts self-assembly into a short rod with average width of 83 nm due to the molecular amphipathy and π-π interaction between naphthalene nucleuses, while P exhibits 20 nm wide line morphology. Irradiating P with 365 nm light, the corresponding aggregation D1 shows as 35 nm wide short rod.

Branched 1,2,3-Triazolium-Functionalized Polyacetylene with Enhanced Conductivity.

Metathesis cyclopolymerization of mono- or bissubstituted 1,6-heptadiynes is undergone to generate the ionic polyacetylenes (iPAs) with branched 1,2,3-ttriazolium pendants, which possess relatively high intrinsic ionic conductivities of 1.4 × 10-5 -2.1 × 10-5 S cm-1 at 30 °C. The doping treatment with lithium bis(trifluoromethanesulfonyl)imide endows iPAs with enhanced ionic conductivities of 2.5 × 10-5 -4.3 × 10-5 S cm-1 . Further doping with iodine, iPAs show ionic and electronic dual conductivities of 4.5 × 10-5 -7.1 × 10-4 and 1.5 × 10-6 -4.5 × 10-6 S cm-1 , respectively. Therefore, the doped iPAs demonstrate the potential in the area of conducting polymers and polymeric electronics.

Impact of preoperative urodynamic testing for urinary incontinence and pelvic organ prolapse on clinical management in Chinese women.

AIM: To assess the impact of preoperative urodynamic testing on the clinical management of urinary incontinence and pelvic organ prolapse. METHODS: Urodynamic testing was performed prior to surgery in 307 patients with pelvic organ prolapse or urinary incontinence. The resulting changes to planned treatment were recorded and retrospectively assessed. RESULTS: Results of urodynamic testing prompted changes to the treatment plan in 136 cases (44.2%), including 86 cases of no or slight-stress urinary incontinence, 28 cases of bladder outlet obstruction, 12 cases of occult stress urinary incontinence and 10 cases of detrusor overactivity and urge urinary incontinence. Urodynamic testing excluded disadvantageous factors in 69 cases (22.4%), including 46 cases of overactive bladder and 23 cases of voiding dysfunction. The information provided to patients when seeking informed consent was augmented by the results of urodynamic testing in 63 cases (20.5%). Urodynamic testing was of no value in 39 cases (12.7%). CONCLUSIONS: Preoperative urodynamic testing for urinary incontinence and pelvic organ prolapse can result in changes to treatment plans, exclusion of disadvantageous factors, and augmentation of information provided to patients when seeking informed consent.

Neuroprotective role of FOXA1 in Parkinson's disease: Involvements of NF1 transcription activation and MAPK signaling pathway inhibition.

Forkhead box A1 (FOXA1), a member of the forkhead family of transcription factors, plays a crucial role in the development of various organ systems and exhibits neuroprotective properties. This study aims to investigate the effect of FOXA1 on Parkinson's disease (PD) and unravel the underlying mechanism. Transcriptome analysis of PD was conducted using three GEO datasets to identify aberrantly expressed genes. A mouse model of PD was generated by injecting neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), resulting in reduced FOXA1 expression. FOXA1 decline was also observed in 1-methyl-4-phenylpyridinium-treated SH-SY5Y cells. Artificial upregulation of FOXA1 improved motor abilities of mice according to rotarod and pole tests, and it mitigated tissue damage, cell loss, and neuronal damage in the mouse substantia nigra or in vitro. FOXA1 was found to bind to the neurofibromin 1 (NF1) promoter, thereby inducing its transcription and inactivating the mitogen-activated protein kinase (MAPK) signaling pathway. Further experimentation revealed that silencing NF1 in mice or SH-SY5Y cells counteracted the neuroprotective effects of FOXA1. In conclusion, this research suggests that FOXA1 activates NF1 transcription and inactivates the MAPK signaling pathway, ultimately ameliorating neuronal damage and motor disability in PD. The findings may offer novel ideas in the field of PD management.

Facile Preparation of Tough, Puncture-Resistant Antibacterial Polyrotaxane Hydrogel.

Slide-ring hydrogels containing polyrotaxane structures have been widely developed, but current methods are more complex, in which modified cyclodextrins, capped polyrotaxanes, and multistep reactions are often needed. Here, a simple one-pot method dissolving the pseudopolyrotaxane (pPRX) in a mixture of acrylamide and boric acid to form a slide-ring hydrogel by UV light is used to construct a tough, puncture-resistant antibacterial polyrotaxane hydrogel. As a new dynamic ring cross-linking agent, boric acid effectively improves the mechanical properties of the hydrogel and involves the hydrogel with fracture toughness. The polyrotaxane hydrogel can withstand 1 MPa compression stress and maintain the morphology integrity, showing 197.5 mJ puncture energy under a sharp steel needle puncture. Meanwhile, its significant antibacterial properties endow the hydrogel with potential applications in the biomedical field.

The effects of bisphenol S exposure on the growth, physiological and biochemical indices, and ecdysteroid receptor gene expression in red swamp crayfish, Procambarus clarkii.

The experiment was conducted to investigate the effects of Bisphenol S (BPS) on growth, physiological and biochemical indices, and the expression of ecdysteroid receptor (ECR) of the red swamp crayfish (Procambarus clarkii). The gene encoding ECR was isolated from red swamp crayfish by homologous cloning and rapid amplification of cDNA ends (RACE). The ECR transcripts were 1757 bp long and encoded proteins of 576 amino acids. The quantitative real-time PCR (qRT-PCR) analysis showed that the ECR gene was expressed in various tissues under normal conditions, and the highest level was observed in the ovary and the lowest level was observed in the muscle (P < 0.05). Then, the experiment was designed with four different BPS concentrations (0, 1, 10, and 100 µg/L), BPS exposure for 14 days, three parallel groups, and a total of 240 red swamp crayfish. At 100 µg/L BPS, the survival rate, weight gain rate, and relative length rate were decreased significantly (P < 0.05). Malonaldehyde (MDA) content reached the highest level at 100 µg/L BPS. When BPS concentration was higher than 10 µg/L, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly lower than those of the control group (P < 0.05). The expression levels of the ECR gene in ovary, intestinal, gill, and hepatopancreas tissues were significantly increased after BPS exposure (P < 0.05). The ECR gene expression in ovaries and Y-organs was significantly higher than other groups in 10 µg/L BPS (P < 0.05). The expressions of the tumor necrosis factor -α (TNF-α) and interleukin-6 (IL-6) genes in the hepatopancreas gradually increased, and the highest expression was observed exposed in 100 µg/L BPS (P < 0.05). This research will provide novel insights into the health risk assessment of BPS in aquatic organisms.

Light-driven linear helical supramolecular polymer formed by molecular-recognition-directed self-assembly of bis(p-sulfonatocalix[4]arene) and pseudorotaxane.

A light-driven, linear, chiral supramolecular polymer was constructed in water by host-guest molecular recognition between bis(p-sulfonatocalix[4]arene) and the α-cyclodextrin-based pseudo[3]rotaxane containing axially chiral 1,1'-binaphthyl and photoresponsive azobenzene moieties. The successful supramolecular polymerization by non-covalent host-guest molecular recognition was confirmed by (1)H NMR spectroscopy and dynamic light scattering (DLS) measurements, and its photoresponsive behavior was investigated by UV-vis absorption spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The chirality of this supramolecular polymer was confirmed by circular dichroism spectroscopy. The dramatic morphology change of this chiral polymer driven by light was observed in SEM, AFM and TEM images. More interestingly, dynamically self-assembled, light-driven, single-helical linear supramolecular polymer molecules with lengths of hundreds of nanometers to micrometers in water were directly observed in their native state using cryo-TEM measurements. The observation of considerably lengthy individual supramolecular polymer molecules indicates that the molecular self-assembly in water by non-covalent host-guest molecular recognition is sufficiently strong to form the supramolecular polymer. Moreover, preliminary molecular modeling was performed to substantiate this interesting photoresponsive supramolecular structure.

Fullerene [60] encapsulated water-soluble supramolecular cage for prevention of oxidative stress-induced myocardial injury.

A water-soluble cube-like supramolecular cage was constructed by an engagement of six molecules through a hydrophobic effect in the water. The obtained cage could perfectly encapsulate one fullerene C60 molecule inside of the cavity and significantly improve the water-solubility of the C60 without changing the original structure. The water-soluble complex was further applied to reduce the reactive oxygen species (R.O.S.) in cardiomyocytes (FMC84) through Akt/Nrf2/HO-1 pathway. Furthermore, in the mouse model of myocardial ischemia-reperfusion injury, the application of C60 was found to be effective in reducing myocardial injury and improving cardiac function. It also reduced the levels of R.O.S. in myocardial tissue, inhibited myocardial apoptosis, and mitigated myocardial inflammatory responses. The present study provides a new guideline for constructing water-soluble C60 and verifies the important role of C60 in preventing oxidative stress-related cardiovascular disease injury.

Untargeted metabolomics of the cochleae from two laryngeally echolocating bats.

High-frequency hearing is regarded as one of the most functionally important traits in laryngeally echolocating bats. Abundant candidate hearing-related genes have been identified to be the important genetic bases underlying high-frequency hearing for laryngeally echolocating bats, however, extensive metabolites presented in the cochleae have not been studied. In this study, we identified 4,717 annotated metabolites in the cochleae of two typical laryngeally echolocating bats using the liquid chromatography-mass spectroscopy technology, metabolites classified as amino acids, peptides, and fatty acid esters were identified as the most abundant in the cochleae of these two echolocating bat species, Rhinolophus sinicus and Vespertilio sinensis. Furthermore, 357 metabolites were identified as significant differentially accumulated (adjusted p-value <0.05) in the cochleae of these two bat species with distinct echolocating dominant frequencies. Downstream KEGG enrichment analyses indicated that multiple biological processes, including signaling pathways, nervous system, and metabolic process, were putatively different in the cochleae of R. sinicus and V. sinensis. For the first time, this study investigated the extensive metabolites and associated biological pathways in the cochleae of two laryngeal echolocating bats and expanded our knowledge of the metabolic molecular bases underlying high-frequency hearing in the cochleae of echolocating bats.

Detection of serum HE4 levels contributes to the diagnosis of lung cancer.

Lung cancer (LC) is the most frequently diagnosed cancer and is the leading cause of cancer-associated death. Serum markers that exhibit high sensitivity and specificity for LC may assist in the diagnosis and prognosis of LC. The banked serum samples from 599 individuals, including 201 healthy controls, 124 patients with benign lung diseases, and 274 LC cases, were used. The serum concentrations of biomarkers were determined by electrochemiluminescence immunoassay and chemiluminescence immunoassay. The results showed that the serum human epididymis secretory protein 4 (HE4) levels in the LC group were significantly higher than in the healthy and benign lung disease groups. The serum levels of HE4, NSE, and CYFRA21-1 were significantly higher in patients with LC compared to those in the benign lung disease group. The area under the area under the curve (AUC) of HE4 for discriminating LC from healthy controls was 0.851 (95% CI, 0.818-0.884) and 0.739 (95% CI, 0.695-0.783), 0.747 (95% CI, 0.704-0.790), 0.626 (95% CI, 0.577-0.676), and 0.700 (95% CI, 0.653-0.747) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 combined with NSE, CYFRA21-1, SCC, and proGRP for cancer diagnosis was 0.896 (95% CI, 0.868-0.923). In early LC, the AUC value of HE4 for discriminating early LC from healthy controls was 0.802 (95% CI, 0.758-0.845), 0.728 (95% CI, 0.679-0.778), 0.699 (95% CI, 0.646-0.752), 0.605 (95% CI, 0.548-0.662), and 0.685 (95% CI, 0.630-0.739) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 with NSE, CYFRA21-1, SCC, and proGRP for early LC was 0.867 (95% CI, 0.831-0.903). Serum HE4 is a promising LC biomarker, particularly for early-stage LC. Measuring serum HE4 levels may improve the diagnostic efficiency of LC.