A nanofluidic spiking synapse.

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.

Platelet-derived TGF-ß1 induces functional reprogramming of myeloid-derived suppressor cells in immune thrombocytopenia.

ABSTRACT: Platelet α-granules are rich in transforming growth factor ß1 (TGF-ß1), which is associated with myeloid-derived suppressor cell (MDSC) biology. Responders to thrombopoietin receptor agonists (TPO-RAs) revealed a parallel increase in the number of both platelets and MDSCs. Here, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to establish an active murine model of immune thrombocytopenia (ITP). Subsequently, we demonstrated that TPO-RAs augmented the inhibitory activities of MDSCs by arresting plasma cells differentiation, reducing Fas ligand expression on cytotoxic T cells, and rebalancing T-cell subsets. Mechanistically, transcriptome analysis confirmed the participation of TGF-ß/Smad pathways in TPO-RA-corrected MDSCs, which was offset by Smad2/3 knockdown. In platelet TGF-ß1-deficient mice, TPO-RA-induced amplification and enhanced suppressive capacity of MDSCs was waived. Furthermore, our retrospective data revealed that patients with ITP achieving complete platelet response showed superior long-term outcomes compared with those who only reach partial response. In conclusion, we demonstrate that platelet TGF-ß1 induces the expansion and functional reprogramming of MDSCs via the TGF-ß/Smad pathway. These data indicate that platelet recovery not only serves as an end point of treatment response but also paves the way for immune homeostasis in immune-mediated thrombocytopenia.

Two-fluid dynamics and micron-thin boundary layers shape cytoplasmic flows in early Drosophila embryos.

Cytoplasmic flows are widely emerging as key functional players in development. In early Drosophila embryos, flows drive the spreading of nuclei across the embryo. Here, we combine hydrodynamic modeling with quantitative imaging to develop a two-fluid model that features an active actomyosin gel and a passive viscous cytosol. Gel contractility is controlled by the cell cycle oscillator, the two fluids being coupled by friction. In addition to recapitulating experimental flow patterns, our model explains observations that remained elusive and makes a series of predictions. First, the model captures the vorticity of cytosolic flows, which highlights deviations from Stokes' flow that were observed experimentally but remained unexplained. Second, the model reveals strong differences in the gel and cytosol motion. In particular, a micron-sized boundary layer is predicted close to the cortex, where the gel slides tangentially while the cytosolic flow cannot slip. Third, the model unveils a mechanism that stabilizes the spreading of nuclei with respect to perturbations of their initial positions. This self-correcting mechanism is argued to be functionally important for proper nuclear spreading. Fourth, we use our model to analyze the effects of flows on the transport of the morphogen Bicoid and the establishment of its gradients. Finally, the model predicts that the flow strength should be reduced if the shape of the domain is more round, which is experimentally confirmed in Drosophila mutants. Thus, our two-fluid model explains flows and nuclear positioning in early Drosophila, while making predictions that suggest novel future experiments.

An Ultrasensitive and Efficient microRNA Nanosensor Empowered by the CRISPR/Cas Confined in a Nanopore.

This work presents a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas-nanopipette nano-electrochemistry (Cas = CRISPR-associated proteins) capable of ultrasensitive microRNA detection. Nanoconfinement of the CRISPR/Cas13a within a nanopipette leads to a high catalytic efficacy of ca. 169 times higher than that in bulk electrolyte, contributing to the amplified electrochemical responses. CRISPR/Cas13a-enabled detection of representative microRNA-25 achieves a low limit of detection down to 10 aM. Practical application of this method is further demonstrated for single-cell and real human serum detection. Its general applicability is validated by addressing microRNA-141 and the SARS-CoV-2 RNA gene fragment. This work introduces a new CRISPR/Cas-empowered nanotechnology for ultrasensitive nano-electrochemistry and bioanalysis.

Single-Cell Caspase-3 Measurement Using a Biomimetic Nanochannel.

Direct single-cell caspase-3 (Casp-3) analysis has remained challenging. A study of single-cell Casp-3 could contribute to revealing the fundamental pathogenic mechanisms in Casp-3-associated diseases. Here, a biomimetic nanochannel capable of single-cell sampling and ionic detection of intracellular Casp-3 is devised, which is established upon the installment of target-specific organic molecules (luc-DEVD) within the orifice of a glass nanopipette. The specific cleavage of luc-DEVD by Casp-3 could induce changes of inner-surface chemical groups and charge properties, thus altering the ionic response of the biomimetic nanochannel for direct Casp-3 detection. The practical applicability of this biomimetic nanochannel is confirmed by probing intracellular Casp-3 fluctuation upon drug stimulation and quantifying the Casp-3 evolution during induced apoptosis. This work realizes ionic single-cell Casp-3 analysis and provides a different perspective for single-cell protein analysis.

Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury.

BACKGROUND: Neuropathic pain (NP) is a kind of intractable pain. The pathogenesis of NP remains a complicated issue for pain management practitioners. SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (SPOCK2) are members of the SPOCK family that play a significant role in the development of the central nervous system. In this study, we investigated the role of SPOCK2 in the development of NP in a rat model of chronic constriction injury (CCI). METHODS: Sprague-Dawley rats were randomly grouped to establish CCI models. We examined the effects of SPOCK2 on pain hpersensitivity and spinal astrocyte activation after CCI-induced NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to reflects the pain behavioral degree. Molecular mechanisms involved in SPOCK2-mediated NP in vivo were examined by western blot analysis, immunofluorescence, immunohistochemistry, and co-immunoprecipitation. In addition, we examined the SPOCK2-mediated potential protein-protein interaction (PPI) in vitro coimmunoprecipitation (Co-IP) experiments. RESULTS: We founded the expression level of SPOCK2 in rat spinal cord was markedly increased after CCI-induced NP, while SPOCK2 downregulation could partially relieve pain caused by CCI. Our research showed that SPOCK2 expressed significantly increase in spinal astrocytes when CCI-induced NP. In addition, SPOCK2 could act as an upstream signaling molecule to regulate the activation of matrix metalloproteinase-2 (MMP-2), thus affecting astrocytic ERK1/2 activation and interleukin (IL)-1ß production in the development of NP. Moreover, in vitro coimmunoprecipitation (Co-IP) experiments showed that SPOCK2 could interact with membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14) to regulate MMP-2 activation by the SPARC extracellular (SPARC_EC) domain. CONCLUSIONS: Research shows that SPOCK2 can interact with MT1-MMP to regulate MMP-2 activation, thus affecting astrocytic ERK1/2 activation and IL-1ß production to achieve positive promotion of NP.

High-Precision Single-Cell microRNA Therapy by a Functional Nanopipette with Sensitive Photoelectrochemical Feedback.

This work proposes the concept of single-cell microRNA (miR) therapy and proof-of-concept by engineering a nanopipette for high-precision miR-21-targeted therapy in a single HeLa cell with sensitive photoelectrochemical (PEC) feedback. Targeting the representative oncogenic miR-21, the as-functionalized nanopipette permits direct intracellular drug administration with precisely controllable dosages, and the corresponding therapeutic effects can be sensitively transduced by a PEC sensing interface that selectively responds to the indicator level of cytosolic caspase-3. The experimental results reveal that injection of ca. 4.4 × 10-20 mol miR-21 inhibitor, i.e., 26488 copies, can cause the obvious therapeutic action in the targeted cell. This work features a solution to obtain the accurate knowledge of how a certain miR-drug with specific dosages treats the cells and thus provides an insight into futuristic high-precision clinical miR therapy using personalized medicine, provided that the prerequisite single-cell experiments are courses of personalized customization.

A novel mouse model of familial combined hyperlipidemia and atherosclerosis.

Within the context of residual cardiovascular risk in post-statin era, emerging evidence from epidemiologic and human genetic studies have demonstrated that triglyceride (TG)-rich lipoproteins and their remnants are causally related to cardiovascular risk. While, carriers of loss-of-function mutations of ApoC3 have low TG levels and are protected from cardiovascular disease (CVD). Of translational significance, siRNAs/antisense oligonucleotide (ASO) targeting ApoC3 is beneficial for patients with atherosclerotic CVD. Therefore, animal models of atherosclerosis with both hypercholesterolemia and hypertriglyceridemia are important for the discovery of novel therapeutic strategies targeting TG-lowering on top of traditional cholesterol-lowering. In this study, we constructed a novel mouse model of familial combined hyperlipidemia through inserting a human ApoC3 transgene (hApoC3-Tg) into C57BL/6 J mice and injecting a gain-of-function variant of adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-D377Y concurrently with high cholesterol diet (HCD) feeding for 16 weeks. In the last 10 weeks, hApoC3-Tg mice were orally treated with a combination of atorvastatin (10 mg·kg-1·d-1) and fenofibrate (100 mg·kg-1·d-1). HCD-treated hApoC3-Tg mice demonstrated elevated levels of serum TG, total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). Oral administration of atorvastatin and fenofibrate significantly decreased the plaque sizes of en face aorta, aortic sinus and innominate artery accompanied by improved lipid profile and distribution. In summary, this novel mouse model is of considerable clinical relevance for evaluation of anti-atherosclerotic drugs by targeting both hypercholesterolemia and hypertriglyceridemia.

Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans.

Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in prokaryotes and eukaryotes is the mismatch repair pathway, which blocks recombination between divergent DNA sequences. Previous studies illuminated the role of the mismatch repair component Msh2 in blocking genetic recombination between divergent DNA during meiosis. Loss of Msh2 results in increased interspecific genetic recombination in bacterial and yeast models, and increased viability of progeny derived from yeast hybrid crosses. Hybrid isolates of two pathogenic fungal Cryptococcus species, Cryptococcus neoformans and Cryptococcus deneoformans, are isolated regularly from both clinical and environmental sources. In the present study, we sought to determine if loss of Msh2 would relax the species boundary between C. neoformans and C. deneoformans. We found that crosses between these two species in which both parents lack Msh2 produced hybrid progeny with increased viability and high levels of aneuploidy. Whole-genome sequencing revealed few instances of recombination among hybrid progeny and did not identify increased levels of recombination in progeny derived from parents lacking Msh2. Several hybrid progeny produced structures associated with sexual reproduction when incubated alone on nutrient-rich medium in light, a novel phenotype in Cryptococcus. These findings represent a unique, unexpected case where rendering the mismatch repair system defective did not result in increased meiotic recombination across a species boundary. This suggests that alternative pathways or other mismatch repair components limit meiotic recombination between homeologous DNA and enforce species boundaries in the basidiomycete Cryptococcus species.

Dual Functional Conjugated Acetylenic Polymers: High-Efficacy Modulation for Organic Photoelectrochemical Transistors and Structural Evolution for Bioelectronic Detection.

Conjugated acetylenic polymers (CAPs) have emerged as a unique class of metal-free semiconductors with tunable electrical and optical properties yet their full potential remains largely unexplored. Organic bioelectronics is envisioned to create more opportunities for innovative biomedical applications. Herein, we report a poly(1,4-diethynylbenzene) (pDEB)/NiO gated enhancement-mode poly(ethylene dioxythiophene)-poly(styrene sulfonate) organic photoelectrochemical transistor (OPECT) and its structural evolution toward bioelectronic detection. pDEB was synthesized via copper-mediated Glaser polycondensation of DEB monomers on the NiO/FTO substrate, and the as-synthesized pDEB/NiO/FTO can efficiently modulate the enhancement-mode device with a high current gain. Linking with a sandwich immunoassay, the labeled alkaline phosphatase can catalyze sodium thiophosphate to generate H2S, which will react with the diacetylene group in pDEB through the Michael addition reaction, resulting in an altered molecular structure and thus the transistor response. Exemplified by HIgG as the model target, the developed biosensor achieves highly sensitive detection with a linear range of 70 fg mL-1-10 ng mL-1 and a low detection limit of 28.5 fg mL-1. This work features the dual functional CAP-gated OPECT, providing not only a novel gating module but also a structurally new rationale for bioelectronic detection.

Alkaline Phosphatase-Mediated Bioetching of CoOOH/BiVO4 for Signal-On Organic Photoelectrochemical Transistor Bioanalysis.

Organic photoelectrochemical transistor (OPECT) bioanalytics has recently appeared as a promising route for biological measurements, which has major implications in both next-generation photoelectrochemical (PEC) bioanalysis and futuristic biorelated implementations. Via biological dissociation of materials, bioetching is a useful technique for bio-manufacturing and bioanalysis. The intersection of these two domains is expected to be a possible way to achieve innovative OPECT bioanalytics. Herein, we validate such a possibility, which is exemplified by alkaline phosphatase (ALP)-mediated bioetching of a CoOOH/BiVO4 gate for a signal-on OPECT immunoassay of human immunoglobulin G (HIgG) as the model target. Specifically, target-dependent bioetching of the upper CoOOH layer could result into an enhanced electrolyte contact and light accessibility to BiVO4, leading to the modulated response of the polymeric poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) channel that could be monitored by the channel current. The introduced biosensor achieves sensitive detection of HIgG with high selectivity and sensitivity. This work features bioetching-enabled high-efficacy OPECT bioanalysis and is anticipated to serve as a generic protocol, considering the diverse bioetching routes.

Autophagy-prominent cell clusters among human lens epithelial cells: integrated single-cell RNA-sequencing analysis.

BACKGROUND: Autophagy is an important process that maintains the quality of intracellular proteins and organelles. There is extensive evidence that autophagy has an important role in the lens. Human lens epithelial cells (HLECs) play a key role in the internal homeostasis of the lens. HLEC subtypes have been identified, but autophagy-prominent cell clusters among HLECs have not been characterized. PURPOSE: To explore the existence of autophagy-prominent cell clusters in HLECs. METHODS: Three donated lenses (HLECs from two whole lenses and HLECs from one lens without the anterior central 6-mm zone) were used for single-cell RNA sequencing (scRNA-seq). AUCell and AddModuleScore analysis were used to identify potential autophagy-prominent cell clusters. Transmission electron microscopy (TEM) was used to confirm the results. RESULTS: High-quality transcripts from 18,120 cells were acquired by scRNA-seq of the two intact lenses. Unsupervised clustering classified the cells into four clusters. AUCell and AddModuleScore analysis revealed cluster 1 is autophagy-prominent. scRNA-seq analysis of HLECs from the lens capsule lacking the central zone confirmed the cluster 1 HLECs was located in the central capsule zone. The TEM result showed that greater autophagy activity was observed in the HLECs in central capsule zone, which further supported the above conclusions based on scRNA-seq analysis that autophagy was prominent in the central zone where the cluster 1 HLECs located. CONCLUSIONS: We identified an autophagy-prominent cell cluster among HLECs and revealed that it was localized in the central zone of the lens capsule. Our findings will aid investigations of autophagy in HLECs and provide insights to guide related research.

Electrochemical Single-Cell Protein Therapeutics Using a Double-Barrel Nanopipette.

Single-cell protein therapeutics is expected to promote our in-depth understanding of how a specific protein with a therapeutic dosage treats the cell without population averaging. However, it has not yet been tackled by current single-cell nanotools. We address this challenge by the use of a double-barrel nanopipette, in which one lumen was used for electroosmotic cytosolic protein delivery and the other was customized for ionic evaluation of the consequence. Upon injection of protein DJ-1 through the delivery lumen, upregulation of the antioxidant protein could protect neural PC-12 cells against oxidative stress from phorbol myristate acetate exposure, as deduced by targeting of the cytosolic hydrogen peroxide by the detecting lumen. The nanotool developed in this study for single-cell protein therapeutics provides a perspective for future single-cell therapeutics involving different therapeutic modalities, such as peptides, enzymes and nucleic acids.

An Integrated Dual-Functional Nanotool Capable of Studying Single-Cell Epigenetics and Programmable Gene Regulation.

Single-cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single-cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6-methyladenine (m6 A)-bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m6 A-modifying enzyme, fat mass and obesity-associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m6 A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO-mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single-cell epigenetics and programmable gene regulation.

Upregulation of KLHL17 promotes the proliferation and migration of non-small cell lung cancer by activating the Ras/MAPK signaling pathway.

Analysis of the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that Kelch-like 17 (KLHL17) is overexpressed in non-small cell lung cancer (NSCLC) including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We therefore explored the role of KLHL17 in the development and progression of NSCLC. Immunohistochemistry and western blotting showed that KLHL17 expression was significantly higher in the tumor tissues from 173 patients with NSCLC, compared with the corresponding non-neoplastic tissue. In addition, upregulated KLHL17 expression was positively correlated with tumor size, lymph node metastasis and tumor node metastasis (TNM) stage, and affected the overall survival (OS) of patients with NSCLC. Consistent with clinical samples, in vitro studies demonstrated that KLHL17 expression was higher in various cell lines of NSCLC (A549, H1299, H460 and SK cells) as compared to normal human bronchial epithelial cells (HBE cells). Overexpression of KLHL17 in the cell lines of NSCLC with KLHL17-Flag plasmid promoted the proliferation and migration of tumor cells, which was associated with elevated activation of Rat sarcoma/Mitogen-activated protein kinases (Ras/MAPK) signaling and increased expression of cyclin D1, cyclin D-dependent kinases 4 (CDK4), matrix metalloproteinase 2 (MMP2) and Ras homolog gene family member A (RhoA). In contrast, knockdown of KLHL17 in the cell lines of NSCLC using KLHL17 small interfering RNA suppressed the proliferation and migration of tumor cells, in association with reduced activation of Ras/MAPK signaling and decreased expression of cyclin D1, CDK4, MMP2 and RhoA. Moreover, treatment of tumor cells with Ras inhibitor salirasib prevented KLHL17-induced Ras/MAPK activity as well as tumor proliferation and migration. These results suggest that upregulated KLHL17 in NSCLC promotes the proliferation and migration of tumor by activating Ras/MAPK signaling pathway. Therefore, KLHL17 may be a novel therapeutic target for the treatment of NSCLC.

Correction of Familial LCAT Deficiency by AAV-hLCAT Prevents Renal Injury and Atherosclerosis in Hamsters-Brief Report.

[Figure: see text].

PCGF3 promotes the proliferation and migration of non-small cell lung cancer cells via the PI3K/AKT signaling pathway.

The Polycomb Group Ring Finger 3 (PCGF3) protein has been reported to be significantly upregulated in pancreatic islet tumors and related to signal transduction; however, its detailed mechanisms and biological roles in other tumors, including non-small cell lung cancer (NSCLC), remain unclear. This study investigated the function of PCGF3 in NSCLC and further elucidated its mechanism of action. The immunohistochemical analysis of 86 selected lung cancer tissues revealed that PCGF3 was highly expressed in NSCLC tissues and positively correlated with lymph node metastasis and p-TNM staging. Additionally, PCGF3 promoted cell proliferation in lung cancer by regulating CyclinB1, CyclinD1, and CDK4 expression, and also promoting their migration by regulating RhoA, RhoC, and CDC42. Furthermore, PCGF3 affected both the proliferation and migration of lung cancer cells by regulating the PI3K/AKT pathway, as verified by inhibiting this pathway using LY294002. The findings of this study suggested that PCGF3 is associated with poor prognosis in patients with NSCLC and could therefore be an important biomarker for treating and preventing NSCLC.

A Photoelectrochemical Nanoreactor for Single-Cell Sampling and Near Zero-Background Faradaic Detection of Intracellular microRNA.

Rational utilization of the rich light-bio-matter interplay taking place in single-cell analysis represents a new technological direction in the field. The light-fueled operation is expected to achieve advanced photoelectrochemical (PEC) single-cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single-cell sampling and near zero-background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target-triggered hybridization chain reaction for binding the metallointercalator of [Ru(bpy)2 (dppz)]2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero-biased and near zero-background PEC method toward Faradaic detection of non-electrogenic miR at the single-cell level. Using this nanotool, lower miR concentration in the near-nucleus region than that in the main cytosol was revealed.

TBC1 domain family member 23 interacts with Ras-related protein Rab-11A to promote poor prognosis of non-small-cell lung cancer via ß1-integrin.

Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases. TBC1D23, a member of the TBC/RABGAP family, is widely expressed in human tissues; however, its role in NSCLC is currently unknown. Immunohistochemical analysis was conducted on 173 paraffin-embedded lung tissue sections from patients with NSCLC from 2014 to 2018 at the First Affiliated Hospital of China Medical University. MTT, colony formation assay, cell cycle assay, scratch assay, transwell assay, Western blotting and real-time PCR were employed on multiple NSCLC cell lines modified to knock down or overexpress TBC1D23/RAB11A. Immunoprecipitation, immunoprecipitation-mass spectrometry, immunofluorescence and flow cytometry were performed to explore the interaction between TBC1D23 and RAB11A and TBC1D23 involvement in the interaction between RAB11A and ß1 integrin in the para-nucleus. TBC1D23 was correlated with tumour size, differentiation degree, metastasis, TNM stage and poor prognosis. TBC1D23 was involved in the interaction between RAB11A and ß1 integrin in the para-nucleus, thus activating the ß1 integrin/FAK/ERK signalling pathway to promote NSCLC. Furthermore, TBC1D23 promoted NSCLC progression by inducing cell proliferation, migration and invasion. This study indicated the relationship between TBC1D23 expression and the adverse clinicopathological characteristics of patients with NSCLC, suggesting that TBC1D23 may be an important target for NSCLC treatment.