CAR directs T cell adaptation to bile acids in the small intestine.

Bile acids are lipid-emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, bile acids can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain bile acid homeostasis in hepatocytes and enterocytes3, but it is unclear how mucosal immune cells tolerate high concentrations of bile acids in the small intestine lamina propria (siLP). CD4+ T effector (Teff) cells upregulate expression of the xenobiotic transporter MDR1 (encoded by Abcb1a) in the siLP to prevent bile acid toxicity and suppress Crohn's disease-like small bowel inflammation4. Here we identify the nuclear xenobiotic receptor CAR (encoded by Nr1i3) as a regulator of MDR1 expression in T cells that can safeguard against bile acid toxicity and inflammation in the mouse small intestine. Activation of CAR induced large-scale transcriptional reprogramming in Teff cells that infiltrated the siLP, but not the colon. CAR induced the expression of not only detoxifying enzymes and transporters in siLP Teff cells, as in hepatocytes, but also the key anti-inflammatory cytokine IL-10. Accordingly, CAR deficiency in T cells exacerbated bile acid-driven ileitis in T cell-reconstituted Rag1-/- or Rag2-/- mice, whereas pharmacological activation of CAR suppressed it. These data suggest that CAR acts locally in T cells that infiltrate the small intestine to detoxify bile acids and resolve inflammation. Activation of this program offers an unexpected strategy to treat small bowel Crohn's disease and defines lymphocyte sub-specialization in the small intestine.

New progress of tuberculosis scar carcinoma.

It has been demonstrated that scar tissue and fibrosis may increase the likelihood of developing malignancies. Specifically, scar tissue has been linked to the occurrence and progression of lung cancer (LC), though the precise mechanisms necessitate further research for explanation. Lung scarring can stem from various causes, with carcinogenesis on scarring lesions in pulmonary tuberculosis (PTB) being the most frequent (accounting for approximately 75% of cases). Notably, having previously cured, PTB is the second most common risk factor for LC after smoking, with approximately 3% of PTB patients experiencing LC as a secondary condition. This essay will delve into the mechanisms, treatment, and prognosis of tuberculosis scar carcinoma (TSC).

Inhibition of RAC attenuates Adriamycin-induced podocyte injury.

Minimal Change Disease (MCD), which is associated with podocyte injury, is the leading cause of nephrotic syndrome in children. A considerable number of patients experience relapses and require prolonged use of prednisone and immunosuppressants. Multi-drug resistance and frequent relapses can lead to disease progression to focal and segmental glomerulosclerosis (FSGS). To identify potential targets for therapy of podocyte injury, we examined microarray data of mRNAs in glomerular samples from both MCD patients and healthy donors, obtained from the GEO database. Differentially expressed genes (DEGs) were used to construct the protein-protein interactions (PPI) network through the application of the search tool for the retrieval of interacting genes (STRING) tool. The most connected genes in the network were ranked using cytoHubba. 16 hub genes were selected and validated by qRT-PCR. RAC2 was identified as a potential therapeutic target for further investigation. By downregulating RAC2, Adriamycin (ADR)-induced human podocytes (HPCs) injury was attenuated. EHT-1864, a small molecule inhibitor that targets the RAC (RAC1, RAC2, RAC3) family, proved to be more effective than RAC2 silencing in reducing HPCs injury. In conclusion, our research suggests that EHT-1864 may be a promising new molecular drug candidate for patients with MCD and FSGS.

A meta-analysis of diabetes risk prediction models applied to prediabetes screening.

AIM: To provide a systematic overview of diabetes risk prediction models used for prediabetes screening to promote primary prevention of diabetes. METHODS: The Cochrane, PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for a comprehensive search period of 30 August 30, 2023, and studies involving diabetes prediction models for screening prediabetes risk were included in the search. The Quality Assessment Checklist for Diagnostic Studies (QUADAS-2) tool was used for risk of bias assessment and Stata and R software were used to pool model effect sizes. RESULTS: A total of 29 375 articles were screened, and finally 20 models from 24 studies were included in the systematic review. The most common predictors were age, body mass index, family history of diabetes, history of hypertension, and physical activity. Regarding the indicators of model prediction performance, discrimination and calibration were only reported in 79.2% and 4.2% of studies, respectively, resulting in significant heterogeneity in model prediction results, which may be related to differences between model predictor combinations and lack of important methodological information. CONCLUSIONS: Numerous models are used to predict diabetes, and as there is an association between prediabetes and diabetes, researchers have also used such models for screening the prediabetic population. Although it is a new clinical practice to explore, differences in glycaemic metabolic profiles, potential complications, and methods of intervention between the two populations cannot be ignored, and such differences have led to poor validity and accuracy of the models. Therefore, there is no recommended optimal model, and it is not recommended to use existing models for risk identification in alternative populations; future studies should focus on improving the clinical relevance and predictive performance of existing models.

Sb2Se3/CdS/ZnO photodetectors based on physical vapor deposition for color imaging applications.

The reported antimony selenide (Sb2Se3) photodetectors (PDs) are still far away from color camera applications mainly due to the high operation temperature required in chemical vapor deposition (CVD) and the lack of high-density PD arrays. In this work, we propose a Sb2Se3/CdS/ZnO PD created by physical vapor deposition (PVD) operated at room temperature. Using PVD, a uniform film can be obtained, so the optimized PD has excellent photoelectric performance with high responsivity (250 mA/W), high detectivity (5.6 × 1012 Jones), low dark current (∼10-9 A), and short response time (rise: < 200 µs; decay: < 200 µs). With the help of advanced computational imaging technology, we successfully demonstrate color imaging applications by the single Sb2Se3 PD; thus, we expect this work can bring Sb2Se3 PDs in color camera sensors closer.

Self-powered and broadband CuSCN/Si heterojunction photodetector for multi-color imaging based on diffuse reflection mode.

Copper thiocyanate (CuSCN) has been widely used in photodetectors (PDs). However, the reported CuSCN-based PDs are suffered from narrow operating wavelength range and relatively low photodetection performance. Here, we fabricate an CuSCN/Si heterojunction PD by a simple low-temperature solution spin-coating method achieving excellent performance. Our designed CuSCN/Si PD exhibits a broadband response range covering ultraviolet-visible-infrared, a high detectivity of 2.26 × 1012Jones coming from an ultralow dark current of 23 pA, and a decent responsivity of 11 mA W-1, a high linear dynamic range of 122 dB, and short response time of 25/150µ(rise and decay time). Moreover, we demonstrate multi-color imaging across the wide wavelength range, indicating the CuSCN/Si PD has a promising potential in the imaging field. This work may pave the way for fabricating low-cost, nontoxicity, and high-performance CuSCN-based PD and broadening its applications.

Circular RNA hsa_circ_0098181 inhibits metastasis in hepatocellular carcinoma by activating the Hippo signaling pathway via interaction with eEF2.

INTRODUCTION AND OBJECTIVES: The development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA. MATERIALS AND METHODS: Ten pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA. RESULTS: CircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis. CONCLUSIONS: Our study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.

Comparison of clinical outcomes of frozen-thawed D5 and D6 blastocysts undergoing preimplantation genetic testing.

BACKGROUND: This study aimed to analyze the clinical outcomes of blastocyst which undergo the preimplantation genetic testing (PGT) transplantation from frozen-thawed D5 and D6. In addition, the effect of blastocyst grade on clinical and neonatal outcomes was also investigated in this study. METHODS: The pregnancy and miscarriage rates of 1130 cycles of frozen embryo transfer, including 784 D5 frozen embryos and 346 D6 frozen embryos in the Reproductive Hospital of Shandong University from January to December 2020 were analyzed. Gardner blastocyst scoring was used for blastocyst evaluation. RESULTS: The pregnancy rate of D5 blastocyst was significantly higher, whereas the miscarriage rate of D5 blastocyst was lower, than that of D6 blastocyst tissue biopsy. No significant difference was observed in birth weight and low birth weight of D5 blastocyst and D6 blastocyst, preterm birth, gestational age, and neonatal sex. Frozen-thawed D5 blastocysts have higher pregnancy success rates and lower miscarriage rates compared to D6 blastocysts. CONCLUSION: Therefore, both blastocyst grade and embryo biopsy date must be considered when transferring frozen embryos.

Mosaic-free compound eye camera based on multidirectional photodetectors and single-pixel imaging.

Compound-eye wide field-of-view (FOV) imaging generally faces the disadvantages of a complex system, low resolution, and complicated image mosaic. Single-pixel imaging has proven to very beneficial in building a high-resolution and simple wide-FOV camera, but its ability to overcome the problem of image mosaics still needs to be demonstrated. In this Letter, we propose a novel, to the best of our knowledge, kind of artificial compound eye based on multidirectional photodetectors (PDs) and demonstrate theoretically and experimentally that mosaics are unnecessary in multidirectional PD-based single-pixel imaging. In addition, we show experimentally that only nine multidirectional PDs are needed to obtain wide-angle images in a hemisphere to realize wide-FOV mosaic-free imaging. This work greatly simplifies the concept of compound-eye cameras and is very enlightening for detector design in wide-FOV single-pixel imaging, plausibly leading to the development of single-pixel endoscopic imaging.

BMSCs improve TNBS-induced colitis in rats by inducing Treg differentiation by expressing PD-L1.

OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BMSCs) show promise in treating inflammatory bowel disease. We tested if BMSCs improve Trinitro-benzene-sulfonic acid (TNBS)-induced colitis by inducing Treg differentiation by modulating programmed cell death 1 ligand 1(PD-L1). RESULTS: BMSCs were isolated and transfected with PD-L1 siRNA. Sprague-Dawley rats were randomly divided into 4 groups: normal, model, BMSC control, and PD-L1 siRNA BMSC. Colitis was induced by TNBS, except in the normal group. On d4, the BMSC control and PD-L1 siRNA BMSC groups were intravenously injected with BMSCs at a dose of 5 × 106 cells in phosphate-buffered saline (PBS; volume matched). BMSCs were later verified to have reached the colon tissue. BMSC control showed significantly better clinical symptoms and reduced histopathological colitis severity; PD-L1 siRNA BMSC group showed no difference. PD-L1 siRNA reduced: spleen and mesenteric lymph node Tregs, PD-L1, interleukin-10 (IL10), phosphate and tension homology deleted on chromosome ten (PTEN); colon p-Akt and p-mTOR were increased. CONCLUSIONS: We found that BMSCs can induce Treg differentiation by inhibiting the Akt/mTOR pathway via PD-L1; this significantly improved symptoms and pathology in our ulcerative colitis rat models.

Enhancing the photodetection performance of MAPbI3 perovskite photodetectors by a dual functional interfacial layer for color imaging.

The color imaging capacity of recently developed perovskite photodetectors (PDs) has not been fully explored. In this Letter, we fabricate a CH3NH3PbI3 (MAPbI3) PD as a color imaging sensor mainly due to its almost flat spectral response in a full visible light region. To enhance the photodetection performance, we introduce a dual functional interfacial TiO2 layer by atomic layer deposition, reducing the dark current to 12 pA from 13 nA and improving the photocurrent to 1.87 µA from 20 nA, resulting in a ∼105 fold enhancement of the ON/OFF ratio. Since we obtained satisfactory color images, we believe that the MAPbI3 perovskite PD is an ideal photosensitive device for color imaging.

Enhanced carrier mobility and tunable electronic properties in α-tellurene monolayer via an α-tellurene and h-BN heterostructure.

Using first-principles calculations within density functional theory, we explore the electronic properties of the α-tellurene/h-BN (Te/BN) heterostructure. We find that the type-I van der Waals (vdW) Te/BN bilayer exhibits an indirect semiconductor property with a bandgap of 0.59 eV, in which both the valence band maximum and conduction band minimum originate from the tellurene monolayer. The very weak interaction between α-tellurene and h-BN monolayers is demonstrated by the small charge transfer between the interlayer. More strikingly, we find that the carrier mobilities in the Te/BN bilayer can reach up to 104 cm2 s-1 V-1, one order of magnitude larger than those in tellurene. The underlying physics is that the Te/BN bilayer dramatically increases the in-plane stiffness as well as reducing the deformation potential compared with the tellurene monolayer. Additionally, we also show that the electronic properties of the Te/BN bilayer can easily be tuned by introducing defects or dopants in the BN monolayer. For instance, the B vacancy makes the Te/BN bilayer undergo the transition from semiconductor to half-metal. Our findings will broaden the potential application of tellurene and provide theoretical guidance for the relative experimental studies on 2D heterobilayers.

Atomic-Layer Deposition-Assisted Double-Side Interfacial Engineering for High-Performance Flexible and Stable CsPbBr3 Perovskite Photodetectors toward Visible Light Communication Applications.

Self-powered photodetectors (PDs) based on inorganic metal halide perovskites are regarded as promising alternatives for the next generation of photodetectors. However, uncontrollable film growth and sluggish charge extraction at interfaces directly limit the sensitivity and response speed of perovskite-based photodetectors. Herein, by assistance of an atomic layer deposition (ALD) technique, CsPbBr3 perovskite thin films with preferred orientation and enlarged grain size are obtained on predeposited interfacial modification layers. Thanks to improved film quality and double side interfacial engineering, the optimized CsPbBr3 (Al2 O3 /CsPbBr3 /TiO2 , ACT) perovskite PDs exhibit outstanding performance with ultralow dark current of 10-11 A, high detectivity of 1.88 × 1013 Jones and broad linear dynamic range (LDR) of 172.7 dB. Significantly, excellent long-term environmental stability (ambient conditions >100 d) and flexibility stability (>3000 cycles) are also achieved. The remarkable performance is credited to the synergistic effects of high carrier conductivity and collection efficiency, which is assisted by ALD modification layers. Finally, the ACT PDs are successfully integrated into a visible light communication system as a light receiver on transmitting texts, showing a bit rate as high as 100 kbps. These results open the window of high performance all-inorganic halide perovskite photodetectors and extends to rational applications for optical communication.

Dual expression of CXCR4 and IL-35 enhances the therapeutic effects of BMSCs on TNBS-induced colitis in rats through expansion of Tregs and suppression of Th17 cells.

Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for the treatment of inflammatory bowel disease owing to their immunosuppressive property and tissue healing potential. The balance between regulatory T cells (Tregs) and T helper (Th)17 cells plays a crucial role in BMSC-mediated immunosuppression. Interleukin (IL)-35 is a newly identified anti-inflammatory cytokine required for the expansion of Tregs and suppression of Th17 cell differentiation. IL-35 can amplify the immunosuppressive property of BMSCs when overexpressed in these cells. However, the reparative capability of BMSCs in vivo is limited, partly due to the poor homing efficiency of BMSCs to inflamed colons. Up-regulation of CXC chemokine receptor 4 (CXCR4) expression in BMSCs may affect the directional homing of implanted BMSCs via stromal-derived factor-1. In this study, by lentivirus-mediated introduction of CXCR4 and IL-35 genes to modify rat BMSCs, we observed enhanced migration and strengthened immunomodulatory activities of the genetically engineering BMSCs. These results suggest that modification of BMSCs by dual expression of CXCR4 and IL-35 may provide an effective therapeutic strategy for inflammatory bowel disease.

MiR-155 contributes to Th17 cells differentiation in dextran sulfate sodium (DSS)-induced colitis mice via Jarid2.

MicroRNAs (miRNAs) play an important role in regulating immune system function by mRNA destabilisation or inhibition of translation. Recently, miR-155 was detected to be significantly up-regulated in colonic tissues of patients with active UC. However, it is unknown whether miR-155 is involved in the pathogenesis of UC and how it influences immune response in dextran sulfate sodium (DSS)-induced colitis mice. Here, we investigated the role of miR-155 in UC. Firstly, through bioinformatics analysis and luciferase report assay, we found Jarid2 was a direct target of miR-155; then, we carried out in situ hybridization, immunofluorescence and flow cytometry, and revealed that miR-155 levels were increased, Jarid2 levels were decreased and the frequency of Th17 cells was elevated in DSS-induced mice; we also used lentiviral vector to deliver miR-155 inhibition sequences to silence miR-155 that was effectively taken up by epithelial cells. MiR-155 inhibition attenuated DSS-induced colonic damage and inhibited Th17 cells differentiation. This study suggests that miR-155 plays a host-damaging role during DSS-induced colitis mice and induces Th17 differentiation by targeting Jarid2.

Mach-Zehnder Interferometer Biochemical Sensor Based on Silicon-on-Insulator Rib Waveguide with Large Cross Section.

A high-sensitivity Mach-Zehnder interferometer (MZI) biochemical sensing platform based on Silicon-in-insulator (SOI) rib waveguide with large cross section is proposed in this paper. Based on the analyses of the evanescent field intensity, the mode polarization and cross section dimensions of the SOI rib waveguide are optimized through finite difference method (FDM) simulation. To realize high-resolution MZI read-out configuration based on the SOI rib waveguide, medium-filled trenches are employed and their performances are simulated through two-dimensional finite-difference-time domain (2D-FDTD) method. With the fundamental EH-polarized mode of the SOI rib waveguide with a total rib height of 10 µm, an outside rib height of 5 µm and a rib width of 2.5 µm at the operating wavelength of 1550 nm, when the length of the sensitive window in the MZI configuration is 10 mm, a homogeneous sensitivity of 7296.6%/refractive index unit (RIU) is obtained. Supposing the resolutions of the photoelectric detectors connected to the output ports are 0.2%, the MZI sensor can achieve a detection limit of 2.74 × 10(-6) RIU. Due to high coupling efficiency of SOI rib waveguide with large cross section with standard single-mode glass optical fiber, the proposed MZI sensing platform can be conveniently integrated with optical fiber communication systems and (opto-) electronic systems, and therefore has the potential to realize remote sensing, in situ real-time detecting, and possible applications in the internet of things.

Design of a High-Performance Micro Integrated Surface Plasmon Resonance Sensor Based on Silicon-On-Insulator Rib Waveguide Array.

Based on silicon-on-insulator (SOI) rib waveguide with large cross-section, a micro integrated surface plasmon resonance (SPR) biochemical sensor platform is proposed. SPR is excited at the deeply etched facet of the bend waveguide by the guiding mode and a bimetallic configuration is employed. With the advantages of SOI rib waveguide and the silicon microfabrication technology, an array of the SPR sensors can be composed to implement wavelength interrogation of the sensors' output signal, so the spectrometer or other bulky and expensive equipment are not necessary, which enables the SPR sensor to realize the miniaturization and integration of the entire sensing system. The performances of the SPR sensor element are verified by using the two-dimensional finite-different time-domain method. The parameters of the sensor element and the array are optimized for the achievement of high performance for biochemical sensing application. As a typical example, a single bimetallic SPR sensor with 3 nm Au over 32 nm Al possesses a high sensitivity of 3.968 × 104 nm/RIU, a detection-accuracy of 14.7 µm(-1). For a uniparted SPR sensor, it can achieve a detection limit of 5.04 × 10(-7) RIU. With the relative power measurement accuracy of 0.01 dB, the refractive index variation of 1.14 × 10(-5) RIU can be detected by the SPR sensor array.

Association of glutathione S-transferase M1, T1, and P1 polymorphisms with renal cell carcinoma: evidence from 11 studies.

The glutathione S-transferases (GSTs) are a gene superfamily of phase II metabolic enzymes that has attracted a considerable attention as a candidate gene for renal cell carcinoma (RCC) based on its enzyme function as a key factor in biotransformation pathways. In the past decade, a number of case-control studies were conducted to investigate the association of GST genetic polymorphisms and RCC risk. However, studies on the association between GST (GSTM1, GSTT1, and GSTP1) polymorphisms and RCC remain to be conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 2,189 cases and 3,817 controls from 11 case-control studies was performed. Overall, the summarized odds ratio for RCC of the GSTM1 null and GSTT1 null polymorphisms was 1.02 (95% confidence interval (CI) 0.91-1.15, P = 0.70) and 1.28 (95% CI 0.96-1.72, P = 0.09), respectively. No significant results were observed in heterozygous and homozygous genotypes when compared with wild-type genotype for GSTP1 I105V polymorphism. However, the GSTM1-GSTT1 interaction analysis showed that the dual null genotype of GSTM1/GSTT1 was significantly associated with an increased RCC risk (odds ratio (OR) = 1.42, 95% CI 1.14-1.76, P = 0.001). In the stratified analyses by ethnicity, significant gene-disease association was obtained among Asians for GSTT1 and GSTP1 polymorphisms. In our meta-analysis, the associations between variations of GSTs and RCC may vary in different ethnic populations, and the interaction between unfavorable GST genotypes may exist.

Bronchial artery chemoembolization in the treatment of refractory central lung cancer with atelectasis.

Objective: This study aims to explore the clinical application of bronchial artery chemoembolization (BACE) in managing refractory central lung cancer with atelectasis. Methods: The retrospective case series includes patients diagnosed with refractory central lung cancer and atelectasis who underwent BACE treatment at Yueyang Integrated Traditional Chinese and Western Medicine Hospital, affiliated with Shanghai University of Traditional Chinese Medicine, from January 2012 to December 2021. Results: All 30 patients with lung cancer successfully underwent BACE procedures. Their ages ranged from 62 to 88 years, with an average age of 67.53. The treatment interval was 21 days, and the treatment cycle ranged from 2 to 12 times, averaging 4.13 times. During the BACE procedures, the Karnofsky Performance Status (KPS) score after 2 to 3 BACE cycles showed a significant improvement (82.0 ± 10.1 vs 68.3 ± 14.0, P < 0.001) than that of before BACE. Only nutritional support and symptomatic treatment were performed after BACE, and no major hemoptysis were observed. During follow-up, 23 cases resulted in mortality, while seven survived. The median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% CI: 4.6-9.4) and 10.0 (95% CI: 6.2-13.8) months, respectively, with 1-, 2-, and 3-year survival rates of 84.0%, 53.5%, and 11.3%, respectively. Eight cases exhibited bronchial recanalization and relief of atelectasis. According to the RECIST scale, there were 4 cases of complete response (CR), 16 cases of partial response (PR), 9 cases of stable disease (SD), and 1 case of progressive disease (PD). No serious adverse events were reported. Conclusion: BACE might be a safe intervention for refractory central lung cancer accompanied by atelectasis. The procedure exhibits satisfactory outcomes in tumor control, atelectasis relief, and enhancement of quality of life, warranting further investigation.

Promising preclinical models for lung cancer research-lung cancer organoids: a narrative review.

Background and Objective: Traditional cell line models are the commonly used preclinical models for lung cancer research. However, cell lines cannot recapitulate the complex tumor heterogeneity and cannot mimic the microenvironment of human cancer. Recently, 3D multicellular in vitro self-assembled models called "organoids" have been developed at a fast pace in the field of research, which can mimic the actual primary tumor. At present, several studies have reported on protocols of lung cancer organoids (LCOs) generation, and using LCOs can provide novel insight into the basic and translational research of lung cancer. However, the establishment of the LCO models remains challenging due to the complexity of lung cancer and the immaturity of organoid technology, so it is necessary to understand the influences of different methodologies on LCO generation and review the applications and limitations of LCO models. Methods: In this review, we searched the literature in the recent ten years in the field of LCOs. Key Content and Findings: We summarized the methodology, the problems, and the solutions in the LCOs generation, its application and limitations, as well as proposing future challenges and perspectives. Conclusions: Currently, LCOs are successfully generated via exploring the methodology by the researchers. Though there are still challenges in clinical application, LCOs are applied in some cancer studies including investigation of anti-cancer treatment response in vitro, modeling tumor immune microenvironment, and construction of organ chips, which are forging a promising path towards precision medicine.