Roles of inflammasomes in viral myocarditis.

Viral myocarditis (VMC), characterized by viral infection-induced inflammation, is a life-threatening disease associated with dilated cardiomyopathy or heart failure. Innate immunity plays a crucial role in the progression of inflammation, in which inflammasomes provide a platform for the secretion of cytokines and mediate pyroptosis. Inflammasomes are rising stars gaining increasing attention. The nucleotide oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, the caspase recruitment domain-containing protein 8 (CARD8) inflammasome, and the caspase-11 inflammasome are three inflammasomes that were reported to affect the process and prognosis of VMC. These inflammasomes can be activated by a wide range of cellular events. Accumulating evidence has suggested that inflammasomes are involved in different stages of VMC, including the trigger and progression of myocardial injury and remodeling after infection. In this review, we summarized the pathways involving inflammasomes in VMC and discussed the potential therapies targeting inflammasomes and related pathways.

Radionuclide-Labeled Microspheres for Radio-Immunotherapy of Hepatocellular Carcinoma.

Brachytherapy, including radioactive seed implantation (RSI) and transarterial radiation therapy embolization (TARE), is an important treatment modality for advanced hepatocellular carcinoma (HCC), but the inability of RSI and TARE to treat tumor metastasis and recurrence limits their benefits for patients in the clinic. Herein, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors-loaded alginate microspheres (IMs) are developed as radionuclide carriers with immunomodulatory functions to achieve effective radio-immunotherapy. The size and swelling properties of IMs can be facilely tailored by adjusting the calcium source during emulsification. Small/large IMs(SIMs/LIMs) are biocompatible and available for RSI and TARE, respectively, after 177 Lu labeling. Among them, 177 Lu-SIMs completely eliminated subcutaneous HCC in mice after intratumoral RSI. Moreover, in combination with anti-PD-L1, 177 Lu-SIMs not only eradicate primary tumors by RSI but also effectively inhibit the growth of distant tumors, wherein the potent abscopal effect can be ascribed to the immune stimulation of RSI and the modulation of the tumor immune microenvironment (TIME) by IDO1 inhibitors. In parallel, LIMs demonstrate excellent embolization efficiency, resulting in visible necrotic lesions in the central auricular artery of rabbits, which are promising for TARE in future studies. Collectively, a versatile therapeutic agent is provided to synchronously modulate the TIME during brachytherapy for efficient radio-immunotherapy of advanced HCC.

Nattokinase-Mediated Regulation of Tumor Physical Microenvironment to Enhance Chemotherapy, Radiotherapy, and CAR-T Therapy of Solid Tumor.

The therapy of solid tumors is always hampered by the intrinsic tumor physical microenvironment (TPME) featured with compact and rigid extracellular matrix (ECM) microstructures. Herein, we introduce nattokinase (NKase), a thrombolytic healthcare drug, to comprehensively regulate the TPME for versatile enhancement of various therapy modalities. Intratumoral injection of NKase not only degrades the major ECM component fibronectin but also inhibits cancer-associated fibroblasts (CAFs) in generating fibrosis, resulting in decreased tumor stiffness, enhanced perfusion, and hypoxia alleviation. The NKase-mediated regulation of the TPME significantly promotes the tumoral accumulation of therapeutic agents, leading to efficient chemotherapy without inducing side effects. Additionally, the enhancement of tumor radiotherapy based on radiosensitizers was also achieved by the pretreatment of intratumorally injected NKase, which could be ascribed to the elevated oxygen saturation level in NKase-treated tumors. Moreover, a xenografted human breast MDB-MA-231 tumor model is established to evaluate the influence of NKase on chimeric antigen receptor (CAR)-T cell therapy, illustrating that the pretreatment of NKase could boost the infiltration of CAR-T cells into tumors and thus be a benefit for tumor inhibition. These findings demonstrate the great promise of the NKase-regulated TPME as a translational strategy for universal enhancement of therapeutic efficacy in solid tumors by various treatments.

Metabolic Homeostasis-Regulated Nanoparticles for Antibody-Independent Cancer Radio-Immunotherapy.

The special metabolic traits of cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) are promising targets for developing novel cancer therapy strategies, especially the glycolysis and mitochondrial energy metabolism. However, therapies targeting a singular metabolic pathway are always counteracted by the metabolic reprogramming of cancer, resulting in unsatisfactory therapeutic effect. Herein, this work employs poly(ethylene glycol)-coated (PEGylated) liposomes as the drug delivery system for both mannose and levamisole hydrochloride to simultaneously inhibit glycolysis and restrain mitochondrial energy metabolism and thus inhibit tumor growth. In combination with radiotherapy, the liposomes can not only modulate the immunosuppressive TME by cellular metabolism regulation to achieve potent therapeutic effect for local tumors, but also suppress the M2 macrophage proliferation triggered by X-ray irradiation and thus enhance the immune response to inhibit metastatic lesions. In brief, this work provides a new therapeutic strategy targeting the special metabolic traits of cancer cells and immunosuppressive TAMs to enhance the abscopal effect of radiotherapy for cancer.

Pleiotropic Immunomodulatory Functions of Radioactive Inactivated Bacterial Vectors for Enhanced Cancer Radio-immunotherapy.

Biomaterial-based pleiotropic immune activation may effectively improve the response rate of immunotherapy and enhance the therapeutic effect of the tumor. Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and immune activation of the body. Herein, we construct an inactivated bacteria vector with 125I/131I labeling (125I-VNP/131I-VNP), which could retain radioiodine at the tumor site for a long time and deliver it into tumor cells and a tumor-associated macrophage (TAM), thus achieving efficient internal radioisotope therapy (IRT) of the primary tumor with good biosafety. More importantly, 131I-VNP-mediated local IRT could further stimulate robust systemic antitumor immune responses via activation of the cGAS-STING pathway of innate immunity and promotion of the maturation of DC cells for T-cell-dominated adaptive immunity. After combination with systemic checkpoint blockade therapy (αPD-L1), 131I-VNP, which induces the up-regulation of PD-L1 expression in the distant tumor, could lead to the inhibition of in situ colon cancer and protection against tumor rechallenge. Our strategy pioneers the use of an inactivated bacteria vector as a bridge to cleverly connect radiotherapy and immunotherapy and provide an enlightening idea for radio-immunotherapy mediated by pleiotropic immune activation functions of bacterial vectors.

Discovery of the Biosynthetic Pathway of Beticolin 1 Reveals a Novel Non-Heme Iron-Dependent Oxygenase for Anthraquinone Ring Cleavage.

This study used light-mediated comparative transcriptomics to identify the biosynthetic gene cluster of beticolin 1 in Cercospora. It contains an anthraquinone moiety and an unusual halogenated xanthone moiety connected by a bicyclo[3.2.2]nonane. During elucidation of the biosynthetic pathway of beticolin 1, a novel non-heme iron oxygenase BTG13 responsible for anthraquinone ring cleavage was discovered. More importantly, the discovery of non-heme iron oxygenase BTG13 is well supported by experimental evidence: (i) crystal structure and the inductively coupled plasma mass spectrometry revealed that its reactive site is built by an atypical iron ion coordination, where the iron ion is uncommonly coordinated by four histidine residues, an unusual carboxylated-lysine (Kcx377) and water; (ii) Kcx377 is mediated by His58 and Thr299 to modulate the catalytic activity of BTG13. Therefore, we believed this study updates our knowledge of metalloenzymes.

131I-αPD-L1 immobilized by bacterial cellulose for enhanced radio-immunotherapy of cancer.

Radioisotope therapy (RIT) of cancer is restrained by the nonspecific distribution of radioisotope and ineptitude for metastatic tumors. Meanwhile, the clinical application of immune checkpoint blockade (ICB) confronts problems such as low responsive rate, multiple administration requirements and immune-related adverse events (irAE). To address these challenges, we prepared an injectable suspension by immobilizing 131I-labeled anti-programmed cell death-ligand 1 antibody (αPD-L1) in bacterial cellulose for precise and durable radio-immunotherapy of cancer. The crisscross network structure of bacterial cellulose nanofibers would contribute to the long-term retention of 131I-labeled αPD-L1 within tumors, which could reduce the side effect stemmed from the nonspecific 131I distribution in normal tissues. The potent long-term RIT of 131I, combined with ICB by αPD-L1, could effectively restrain the growth of primary tumor in mice. In addition to the direct killing effect, 131I-αPD-L1 immobilized by bacterial cellulose could enhance the immunogenic cell death (ICD) of cancer cells, activating the maturation of multiple immune cells to induce a systemic anti-tumor immune effect. Our therapeutic strategy could suppress spontaneous cancer metastasis and prolong the survival time of tumor-bearing mice. This study proposed a new approach for combined radio-immunotherapy and a novel solution for tumor metastasis in advanced-stage cancers.

A real-time 3D electromagnetic navigation system for percutaneous transforaminal endoscopic discectomy in patients with lumbar disc herniation: a retrospective study.

BACKGROUND: In this study, we present a novel electromagnetic navigation (EMN) system for percutaneous transforaminal endoscopic discectomy (PTED) procedure. The objective of this study was to investigate the safety and effectiveness of the PTED with the assistance of the EMN system and compare it with the conventional PTED with the assistance of fluoroscopic guidance (C-arm). METHODS: The clinical data of 79 patients (32 in EMN group and 47 in C-arm group) undergoing PTED for lumbar disc herniation (LDH) from January to September of 2019 were analyzed retrospectively. The radiation time, puncture time, operation time, visual analog scale (VAS), Oswestry disability index (ODI), modified MacNab criteria, and radiological parameters were recorded in both groups. RESULTS: Radiation time, puncture time, and operation time were significantly reduced in the EMN group compared with the C-arm group (P < 0.05). Compared with the C-arm group, a steeper learning curve was observed in the EMN group. There were no significant differences between the two groups regarding VAS and ODI scores at different time points (P > 0.05). The satisfaction rates of the EMN and C-arm groups were 90.63 and 87.23%, respectively, but no significant difference was found between the two groups (P > 0.05). There was no significant difference regarding translation and angular motion between the two groups at preoperation and postoperation (P > 0.05). CONCLUSIONS: The EMN system can be applied to facilitate the PETD procedure. It can significantly reduce the intraoperative radiation time, puncture time, and operation time, and reshape the learning curve of PTED. Due to limitations of a retrospective study, results may need validation with larger prospective randomized clinical trials.

Cell Proliferation and Tumor Induction by Ochratoxin A in Mouse Skin and Evaluation of Cyclin D1 and Cyclooxygenase-2 Expressions.

Motivation. Skin tumor is one of the frequent occurring forms of cancer where 2-3 million instances are reported worldwide. The ultraviolet rays along with the environmental pollutants and other contaminants can be the potential factors of skin cancer. Cyclin D1 is a serious gene included in controlling the development through the G1 phase of the cell cycle. Ochratoxin A (OTA) is a naturally existing mycotoxin which majorly occurs in food like grains. It is responsible for producing the splitting of single-strand DNA and is identified to be cancer-causing. It is established as a critical risk factor towards reproductive health in both males and females. Methodology. A single dose of ochratoxin A was used for topical application for assessment of skin tumor promotion activity, hyperplasia, ornithine decarboxylase activity, and expression of cyclin D1 and COX-2 in mouse skin. Enhancement in the synthesis of DNA, activation of the epidermal growth factor receptor, and overexpression of cyclin D1 and COX-2 were noted. Primary murine keratinocyte cell culture was cultured with Waymouth's medium. Western blot analysis and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of cyclin D1 and COX-2. Chromatin immunoprecipitation (ChIP) assays were used to the association between AP-1 transcription and nuclear factor-kappaB (NF-κB) with COX-2 and cyclin D1 promoters. Results. The results found that cyclin D1 and COX-2 were responsible for stimulating OTA-induced PMK proliferation and hyperplasia. Implications. EGFR-mediated pathways were also responsible for tumor promotion due to OTA.

Diagnosis of pulmonary nodules by DNA methylation analysis in bronchoalveolar lavage fluids.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality. The alteration of DNA methylation plays a major role in the development of lung cancer. Methylation biomarkers become a possible method for lung cancer diagnosis. RESULTS: We identified eleven lung cancer-specific methylation markers (CDO1, GSHR, HOXA11, HOXB4-1, HOXB4-2, HOXB4-3, HOXB4-4, LHX9, MIR196A1, PTGER4-1, and PTGER4-2), which could differentiate benign and malignant pulmonary nodules. The methylation levels of these markers are significantly higher in malignant tissues. In bronchoalveolar lavage fluid (BALF) samples, the methylation signals maintain the same differential trend as in tissues. An optimal 5-marker model for pulmonary nodule diagnosis (malignant vs. benign) was developed from all possible combinations of the eleven markers. In the test set (57 tissue and 71 BALF samples), the area under curve (AUC) value achieves 0.93, and the overall sensitivity is 82% at the specificity of 91%. In an independent validation set (111 BALF samples), the AUC is 0.82 with a specificity of 82% and a sensitivity of 70%. CONCLUSIONS: This model can differentiate pulmonary adenocarcinoma and squamous carcinoma from benign diseases, especially for infection, inflammation, and tuberculosis. The model's performance is not affected by gender, age, smoking history, or the solid components of nodules.

Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression.

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, in vitro and in vivo tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1 expression.

Phytoactinopolyspora limicola sp. nov., an alkaliphilic actinomycete isolated from a soda alkali-saline soil.

An alkaliphilic actinomycete, designated HAJB-30 T, was isolated from a soda alkali-saline soil in Heilongjiang, Northeast China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain HAJB-30 T was most closely related to type strains of the genus Phytoactinopolyspora with sequence similarities ranging between 93.5 and 98.9%. Strain HAJB-30 T grew at pH 8.0-11.0 (optimum pH 9.5-10.0) and in the presence of 0-7.0% NaCl (optimum 1.0-3.0%). Whole-cell hydrolysates of the isolate contained LL-diaminopimelic acid as the diagnostic diamino acid and mannose and rhamnose as diagnostic sugars. The major fatty acids identified were iso-C14:0, iso-C15:0, anteiso-C15:0, iso-C16:0 and anteiso-C17:0, while the menaquinone was MK-9(H4). The genome (6,589,901 bp), composed of 50 contigs, had a G + C content of 66.8%. Out of the 6074 predicted genes, 6020 were protein-coding genes, and 54 were ncRNAs. Digital DNA-DNA hybridization (dDDH) estimation and average nucleotide identity (ANI) of strain HAJB-30 T against genomes of the type strains of related species in the same family ranged between 19.7 and 22.0% and between 71.5 and 76.8%, respectively. From these results, it was concluded that strain HAJB-30 T possesses sufficient characteristics differentiated from all recognized Phytoactinopolyspora species, it is considered to be a novel species for which the name Phytoactinopolyspora limicola sp. nov. is proposed. The type strain is HAJB-30 T (= CGMCC 4.7591 T, = JCM 33694 T).

A Comparison of Efficacy and Safety of Fractional Carbon Dioxide Laser and Fractional Er:YAG Laser for the Treatment of Xanthelasma Palpebrarum: A Two-Center Randomized Split-Face Controlled Trial.

Background: Xanthelasma palpebrarum (XP) is a form of cutaneous xanthoma that presents as collections of yellowish papules or plaques around the eyelids or canthus, affecting patients cosmetically. Objective: This study aimed to compare the efficacy and safety of fractional carbon dioxide (CO2) laser to that of fractional Er:YAG laser for the treatment of XP. Methods: Two centers recruited patients diagnosed with XP of bilaterally symmetrical lesions. The lesion on one side was randomly assigned to be treated with fractional CO2 laser while the lesion on the other side was treated with fractional Er:YAG laser. All subjects received up to five treatments, with a 4-week interval between each treatment. Results: Thirty-nine patients completed the study and a total of 82 lesions were available for final assessment. The percentage of "Excellent Improvement" on third and fourth visit was 60.98% versus 39.02% and 90.24% versus 63.41%, respectively, p < 0.05. In a follow-up for 12 to 25 months, the number of lesions recurred on the side treated with fractional CO2 laser and fractional Er:YAG laser are 9 (22%) and 10 (24%), respectively. Conclusions: In this study, fractional CO2 laser therapy appears superior since a fewer treatments are required for patients to show significant clinical improvement.

Alcanivorax limicola sp. nov., isolated from a soda alkali-saline soil.

An alkaliphilic and aerobic bacterium, designated as strain JB21T, was isolated from a soda alkali-saline soil sample in Heilongjiang, Northeast China. Strain JB21T is a Gram-stain-negative, rod-shaped, non-motile and amylase-positive bacterium. Growth occurred at 15-45 °C (optimum, 35-37 °C), in the presence of 0-15.0% (w/v) NaCl (optimum, 1.0%) and at pH 6.5-10.5 (optimum, pH 8.5-9.5). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain JB21T was most closely related to type strains of the genus Alcanivorax, with the highest sequence similarity to Alcanivorax indicus SW127T (96.3%), and shared 95.4-93.1% sequence identity with other valid type strains of this genus. The major cellular fatty acids identified were C16:0 and summed feature 8 (C18:1ω6c and/or C18:1ω7c). The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol and one unidentified phospholipid. The genomic G + C content of strain JB21T was 61.3 mol%. The digital DNA-DNA hybridization (dDDH) estimation and average nucleotide identity (ANI) between strain JB21T and type strains of the genus Alcanivorax were 18.3-23.2% and 69.2-79.0%, respectively. On the basis of its phenotypic and phylogenetic characteristics, we suggest the creation of a new species within the Alcanivorax genus, named Alcanivorax limicola sp. nov., type strain JB21T (= CGMCC 1.16632T = JCM 33717T).

Effect of different designs of interspinous process devices on the instrumented and adjacent levels after double-level lumbar decompression surgery: A finite element analysis.

Recently, various designs and material manufactured interspinous process devices (IPDs) are on the market in managing symptomatic lumbar spinal stenosis (LSS). However, atraumatic fracture of the intervening spinous process has been reported in patients, particularly, double or multiple level lumbar decompression surgery with IPDs. This study aimed to biomechanically investigate the effects of few commercial IPDs, namely DIAMTM, CoflexTM, and M-PEEK, which were implanted into the L2-3, L3-4 double-level lumbar spinal processes. A validated finite element model of musculoskeletal intact lumbar spinal column was modified to accommodate the numerical analysis of different implants. The range of motion (ROM) between each vertebra, stiffness of the implanted level, intra stress on the intervertebral discs and facet joints, and the contact forces on spinous processes were compared. Among the three implants, the Coflex system showed the largest ROM restriction in extension and caused the highest stress over the disc annulus at the adjacent levels, as well as the sandwich phenomenon on the spinous process at the instrumented levels. Further, the DIAM device provided a superior loading-sharing between the two bridge supports, and the M-PEEK system offered a superior load-sharing from the superior spinous process to the lower pedicle screw. The limited motion at the instrumented segments were compensated by the upper and lower adjacent functional units, however, this increasing ROM and stress would accelerate the degeneration of un-instrumented segments.

Mutant BCL11B in a Patient With a Neurodevelopmental Disorder and T-Cell Abnormalities.

Background: BCL11B encodes B-cell lymphoma/leukemia 11B, a transcription factor that participates in the differentiation and migration of neurons and lymphocyte cells. De novo mutations of BCL11B have been associated with neurodevelopmental disorder and immunodeficiency, such as immunodeficiency 49 (IMD49) and intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities (IDDSFTA). However, the pathogenesis of the neurodevelopmental disorder and T-cell deficiency is still mysterious. The strategy to distinguish these two diseases in detail is also unclear. Methods: A patient with unique clinical features was identified. Multiple examinations were applied for evaluation. Whole-exome sequencing (WES) and Sanger sequencing were also performed for the identification of the disease-causing mutation. Results: We reported a 17-month-old girl with intellectual disability, speech impairment, and delay in motor development. She presented with mild dysmorphic facial features and weak functional movement. MRI indicated the abnormal myelination of the white matter. Immunological analysis showed normal levels of RTEs and γδT cells but a deficiency of naive T cells. Genetic sequencing identified a de novo heterozygous frameshift mutation c.1192_1196delAGCCC in BCL11B. Conclusions: An IDDSFTA patient of East Asian origin was reported. The unreported neurological display, immunophenotype, and a novel disease-causing mutation of the patient extended the spectrum of clinical features and genotypes of IDDSFTA.

Macrophage polarization in atherosclerosis.

Atherosclerosis is a chronic inflammatory response that increases the risk of cardiovascular diseases. An in-depth study of the pathogenesis of atherosclerosis is critical for the treatment of atherosclerotic cardiovascular disease. The development of atherosclerosis involves many cells, such as endothelial cells, vascular smooth muscle cells, macrophages, and others. The considerable effects of macrophages in atherosclerosis are inextricably linked to macrophage polarization and the resulting phenotype. Moreover, the significant impact of macrophages on atherosclerosis depend not only on the function of the different macrophage phenotypes but also on the relative ratio of different phenotypes in the plaque. Research on atherosclerosis therapy indicates that the reduced plaque size and enhanced stability are partly due to modulating macrophage polarization. Therefore, regulating macrophage polarization and changing the proportion of macrophage phenotypes in plaques is a new therapeutic approach for atherosclerosis. This review provides a new perspective for atherosclerosis therapy by summarizing the relationship between macrophage polarization and atherosclerosis, as well as treatment targeting macrophage polarization.

Diminishing microbiome richness and distinction in the lower respiratory tract of lung cancer patients: A multiple comparative study design with independent validation.

OBJECTIVES: Current evidence suggests that microorganisms are associated with neoplastic diseases; however, the role of the airway microbiome in lung cancer remains unknown. To investigate the taxonomic profiles of the lower respiratory tract (LRT) microbiome in patients with lung cancer. MATERIALS AND METHODS: BALF samples were collected in a discovery set comprising 150 individuals, including 91 patients with lung cancer, 29 patients with nonmalignant pulmonary diseases and 30 healthy subjects, and an independent validation set including 85 participants. The samples were assessed by metagenomics analysis. Random forest regression analysis was performed to select a diagnostic panel. RESULTS: In the discovery set, richness was reduced in lung cancer patients compared with that in healthy subjects, and the microbiome of patients with nonmalignant diseases resembled that of patients with lung cancer. Interestingly, Bradyrhizobium japonicum was only found in patients with lung cancer, whereas Acidovorax was found in patients with cancer and nonmalignant pulmonary diseases. A microbiota-related diagnostic model consisting of age, pack year of smoking and eleven types of bacteria was built, and the area under the curve (AUC) for discriminating the patients with cancer was 0.882 (95%CI: 0.807-0.957) in the training set and 0.796 (95%CI: 0.673-0.920) in the independent validation set. CONCLUSION: Our study demonstrates that the LRT microbiome richness is diminished in lung cancer patients compared with that in healthy subjects and that microbiota-specific biomarkers may be useful for diagnosing patients for whom lung biopsy is not feasible.