Injury-mechanism directness as a key factor for fracture laterality in pediatric extremity fractures.

BACKGROUND: Associations between certain extremity fracture sites and laterality in pediatric trauma are well known, whereas the rationale for such laterality tendencies are unclear. We hypothesized that the laterality tendency of a specific fracture would be affected by directness of injury mechanism and not by the fracture site itself. METHODS: We retrospectively enrolled 1382 children (aged 2-16 years) who were diagnosed with extremity fractures sustained during loss-of-balance situations and investigated the laterality tendencies (dominant vs. non-dominant extremity) of specific fracture sites. Multivariate analyses were sequentially performed to adjust for potential confounding variables-with and without injury-mechanism directness as a covariate. RESULTS: In the upper extremities, the non-dominant side was more prone to fractures (p < 0.001), especially of the distal supracondylar humerus, radial and/or ulnar shaft, and distal radius. In the lower extremities, the dominant side was more frequently fractured (p < 0.001), especially at the tibial shaft and distal tibia. However, the predisposing effects of specific fracture sites on fracture laterality were not statistically significant when in analysis adjusted for injury-mechanism directness as a covariate. Fracture laterality was affected by whether the injury mechanism was direct or indirect. Indirect injury to the upper extremity was strongly associated with non-dominant arm injury (odds ratio 0.686 [95% CI 0.517-0.991]; p = 0.009), whereas indirect injury to the lower extremity was strongly associated with dominant leg injury (odds ratio 2.138 [95% CI 1.444-3.165]; p < 0.001). CONCLUSIONS: Injury-mechanism directness, rather than fracture site itself, is a key factor that affects fracture laterality in pediatric extremity fractures. These findings are helpful for improving our understanding of which factors may affect fracture laterality among children.

Forte ceramic-on-delta ceramic cementless total hip arthroplasty: an 8- to 15-year follow-up study.

INTRODUCTION: Forte ceramic head on delta ceramic liner articulation showed satisfactory midterm results without ceramic-related complication. We aimed to investigate the clinical and radiological outcomes of cementless total hip arthroplasty (THA) with forte ceramic head on delta ceramic liner articulation. MATERIALS AND METHODS: Overall, 107 patients (57 men, 50 women; 138 hips) who underwent cementless THA with forte ceramic head on delta ceramic liner articulation were enrolled. The mean follow-up duration was 11.6 years. For the clinical assessments, Harris hip score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), presence of thigh pain, and presence of squeaking were evaluated. Radiographs were assessed to search for osteolysis, stem subsidence, loosening of implants. Kaplan-Meier survival curves were evaluated. RESULTS: The mean HHS and WOMAC improved from 57.1 and 28.1 preoperatively to 81.4 and 13.1 at the final follow-up, respectively. Nine revisions (6.5%) were performed; 5 hips for stem loosening, 1 hip for ceramic liner fracture, 2 hips for periprosthetic fracture, and 1 hip for progressive osteolysis around cup and stem. Thirty-two patients (37 hips) complained squeaking, in which 4 cases (2.9%) were identified as ceramic-related noises. After a mean follow-up period of 11.6 years, 91% (95% CI 87.8-94.2) were free from revision of both femoral and acetabular components due to any reason. CONCLUSIONS: Cementless THA with forte ceramic-on-delta ceramic articulation showed acceptable clinical and radiological results. Serial surveillance of these patients should be performed due to the possibility of cerami- related complications such as squeaking, osteolysis, and ceramic liner fracture.

Phosphoproteome Profiling Using an Isobaric Carrier without the Need for Phosphoenrichment.

Phosphorylation is a crucial component of cellular signaling cascades. It controls a variety of biological cellular functions, including cell growth and apoptosis. Owing to the low stoichiometry of phosphorylated proteins, the enrichment of phosphopeptides prior to LC-MS/MS is necessary for comprehensive phosphoproteome analysis, and quantitative phosphoproteomic workflows are typically limited by the amount of sample required. To address this issue, we developed an easy-to-establish, widely applicable, and reproducible strategy to increase phosphoproteomic signals from a small amount of sample without a phosphoenrichment step. By exploiting the multiplexing nature of isobaric labeling to generate a merged signal from multiple samples, and using a larger amount of enriched phosphopeptides as a carrier, we were able to increase trace amounts of phosphopeptides in the unpurified sample to an identifiable level and perform quantification using the reporter ion intensity of the isobaric tag. Our results showed that >1400 phosphopeptides were quantified from 250 ng of tryptic peptides prepared from cells. In a proof-of-concept of our strategy, we distinguished three types of lung cancer cell lines based on their quantitative phosphoproteomic data and identified changes in the phosphoproteome induced by drug treatment.

Characterization of the Secretome of a Specific Cell Expressing Mutant Methionyl-tRNA Synthetase in Co-Culture Using Click Chemistry.

Co-culture system, in which two or more distinct cell types are cultured together, is advantageous in that it can mimic the environment of the in vivo niche of the cells. In this study, we presented a strategy to analyze the secretome of a specific cell type under the co-culture condition in serum-supplemented media. For the cell-specific secretome analysis, we expressed the mouse mutant methionyl-tRNA synthetase for the incorporation of the non-canonical amino acid, azidonorleucine into the newly synthesized proteins in cells of which the secretome is targeted. The azidonorleucine-tagged secretome could be enriched, based on click chemistry, and distinguished from any other contaminating proteins, either from the cell culture media or the other cells co-cultured with the cells of interest. In order to have more reliable true-positive identifications of cell-specific secretory bodies, we established criteria to exclude any identified human peptide matched to bovine proteins. As a result, we identified a maximum of 719 secreted proteins in the secretome analysis under this co-culture condition. Last, we applied this platform to profile the secretome of mesenchymal stem cells and predicted its therapeutic potential on osteoarthritis based on secretome analysis.

tipNrich: A Tip-Based N-Terminal Proteome Enrichment Method.

The mass spectrometry-based analysis of protein post-translational modifications requires large amounts of sample, complicating the analysis of samples with limited amounts of proteins such as clinical biopsies. Here, we present a tip-based N-terminal analysis method, tipNrich. The entire procedure is processed in a single pipette tip to minimize sample loss, which is so highly optimized to analyze small amounts of proteins, even femtomole-scale of a single protein. With tipNrich, we investigated various single proteins purified from different organisms using a low-resolution mass spectrometer and identified several N-terminal peptides with different Nt-modifications such as ragged N-termini. Furthermore, we applied matrix-assisted laser desorption ionization time-of-flight mass spectrometry to our method for shortening the analysis time. Moreover, we showed that our method could be utilized in disease diagnosis as exemplified by the characterization of wild-type transthyretin amyloidosis patients compared to the healthy individuals based on N-terminome profiling. In summary, tipNrich will satisfy the need of identifying N-terminal peptides even with highly scarce amounts of proteins and of having faster processing time to check the quality of protein products or to characterize N-terminal proteoform-related diseases.

Postoperative Pain Control After Arthroscopic Rotator Cuff Repair: Arthroscopy-Guided Continuous Suprascapular Nerve Block Versus Ultrasound-Guided Continuous Interscalene Block.

PURPOSE: To compare the clinical efficacy and safety of arthroscopy-guided continuous suprascapular nerve block and ultrasound-guided continuous interscalene block in postoperative analgesia in patients undergoing arthroscopic rotator cuff repair. METHODS: A prospective study was performed between March and November 2020. In total, 76 patients were enrolled and divided into 2 groups: in the 38 patients of group 1 (arthroscopy-guided continuous suprascapular nerve block), an indwelling catheter was introduced via the Neviaser portal under arthroscopic view before closing the portal at the end of the surgery; and in the 38 patients of group 2 (ultrasound-guided continuous interscalene block), an indwelling catheter was inserted and directed toward the interscalene brachial plexus prior to the surgery under ultrasound guidance. The primary outcome was the pain score measured by the visual analog scale at postoperative 24 hours during admission. Comparisons were conducted at different time points (postoperative 4, 8, 24, and 48 hours). The secondary outcome was any of these events: neurologic complications, such as sensory/motor change in the upper extremities; hemidiaphragmatic paresis; dyspnea; dysphonia; and Horner's syndrome. Opioid usage until postoperative 3 weeks was compared between the groups. RESULTS: The visual analog scale scores in groups 1 and 2 were comparable at each postoperative time point (analysis of variance, P = .919; trends, P = .132). Neurologic deficits were more common in group 2 than in group 1 (8 vs 32 patients, P < .001). Decreased excursion of the diaphragm was more common in group 2 (partial or complete paresis of the hemidiaphragm: 1 vs 29 patients, P < .001). Opioid consumption was similar in both groups (morphine milligram equivalents per kilogram; 1.75 vs 1.55, P = .195). CONCLUSIONS: Our findings show that arthroscopy-guided continuous suprascapular nerve block is not inferior to ultrasound-guided continuous interscalene block for postoperative pain control after arthroscopic rotator cuff repair while showing fewer temporary neurologic complications. LEVEL OF EVIDENCE: Level II, prospective cohort study, interventional study.

Complications and safety of the transplanted organ after upper extremity surgery in patients receiving immunosuppressant therapy after solid organ transplantation.

PURPOSE: The purpose of this study was to evaluate the complications and safety of transplanted organs after upper extremity surgery in patients taking immunosuppressants after solid organ transplantation (SOT). METHODS: Seventy-two transplant recipients underwent 99 upper extremity surgeries while on immunosuppressants after SOT at our institution between January 2009 and December 2018. We retrospectively reviewed the clinical data of these patients, including their demographic information and data related to the SOT and upper extremity surgery. RESULTS: Trigger/tendon release (n = 31, 31.3%) was the most frequently performed upper extremity surgery, followed by incision and drainage for an infection (n = 16, 16.2%). Post-operative complications occurred after ten upper extremity operative procedures (10.1%), among which uncontrolled infection after surgery for an infection (n = 4) was the most common. According to the Clavien-Dindo classification, the complications of three surgical procedures were grade I, three were grade II, and four were grade III, and all were treatable. The occurrence rate of the complications was not significantly different between emergent and elective surgery. All transplanted organ-specific indicators did not worsen significantly after emergent or elective upper extremity surgery. CONCLUSIONS: Since the function of the transplanted organ was well-preserved after emergent or elective upper extremity surgery, common upper extremity procedures do not seem to be a worrisome practice for SOT patients. However, when treating hand and upper extremity infections in SOT patients, surgeons should explain the possible need for multiple operations  and the high complication rate.

iNrich, Rapid and Robust Method to Enrich N-Terminal Proteome in a Highly Multiplexed Platform.

The field of terminal proteomics is limited in that it is optimized for large-scale analysis via multistep processes involving liquid chromatography. Here, we present an integrated N-terminal peptide enrichment method (iNrich) that can handle as little as 25 µg of cell lysate via a single-stage encapsulated solid-phase extraction column. iNrich enables simple, rapid, and reproducible sample processing, treatment of a wide range of protein amounts (25 µg ∼ 1 mg), multiplexed parallel sample preparation, and in-stage sample prefractionation using a mixed-anion-exchange filter. We identified ∼5000 N-terminal peptides (Nt-peptides) from only 100 µg of human cell lysate including Nt-formyl peptides. Multiplexed sample preparation facilitated quantitative and robust enrichment of N-terminome with dozens of samples simultaneously. We further developed the method to incorporate isobaric tags such as a tandem mass tag (TMT) and used it to discover novel peptides during ER stress analysis. The iNrich facilitated high-throughput N-terminomics and degradomics at a low cost using commercially available reagents and apparatus, without requiring arduous procedures.

Common Repository of FBS Proteins (cRFP) To Be Added to a Search Database for Mass Spectrometric Analysis of Cell Secretome.

We propose to use cRFP (common Repository of FBS Proteins) in the MS (mass spectrometry) raw data search of cell secretomes. cRFP is a small supplementary sequence list of highly abundant fetal bovine serum proteins added to the reference database in use. The aim behind using cRFP is to prevent the contaminant FBS proteins from being misidentified as other proteins in the reference database, just as we would use cRAP (common Repository of Adventitious Proteins) to prevent contaminant proteins present either by accident or through unavoidable contacts from being misidentified as other proteins. We expect it to be widely used in experiments where the proteins are obtained from serum-free media after thorough washing of the cells, or from a complex media such as SILAC, or from extracellular vesicles directly.

SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.

Proteogenomic Characterization Reveals Estrogen Signaling as a Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR or ALK Alterations.

Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, particularly in women. EGFR mutations and anaplastic lymphoma kinase (ALK) fusions are major genetic alterations observed in NSLA, and NSLA with these alterations have been well studied and can be treated with targeted therapies. To provide insights into the molecular profile of NSLA without EGFR and ALK alterations (NENA), we selected 141 NSLA tissues and performed proteogenomic characterization, including whole genome sequencing (WGS), transcriptomic, methylation EPIC array, total proteomic, and phosphoproteomic analyses. Forty patients with NSLA harboring EGFR and ALK alterations and seven patients with NENA with microsatellite instability were excluded. Genome analysis revealed that TP53 (25%), KRAS (22%), and SETD2 (11%) mutations and ROS1 fusions (14%) were the most frequent genetic alterations in NENA patients. Proteogenomic impact analysis revealed that STK11 and ERBB2 somatic mutations had broad effects on cancer-associated genes in NENA. DNA copy number alteration analysis identified 22 prognostic proteins that influenced transcriptomic and proteomic changes. Gene set enrichment analysis revealed estrogen signaling as the key pathway activated in NENA. Increased estrogen signaling was associated with proteogenomic alterations, such as copy number deletions in chromosomes 14 and 21, STK11 mutation, and DNA hypomethylation of LLGL2 and ST14. Finally, saracatinib, an Src inhibitor, was identified as a potential drug for targeting activated estrogen signaling in NENA and was experimentally validated in vitro. Collectively, this study enhanced our understanding of NENA NSLA by elucidating the proteogenomic landscape and proposed saracatinib as a potential treatment for this patient population that lacks effective targeted therapies. SIGNIFICANCE: The proteogenomic landscape in never-smoker lung cancer without known driver mutations reveals prognostic proteins and enhanced estrogen signaling that can be targeted as a potential therapeutic strategy to improve patient outcomes.

LEGO-like Assembly of Fibrous Modules for Display Textiles.

Due to their promising advantages over classical rigid devices, the development of display textiles has exciting potential for various fields, including sensor technology, healthcare, and communication. To realize display textiles, it is necessary to prepare light-emitting building blocks at the fiber level and then weave or knit them to form the desired textile structures. However, from a practical viewpoint, it is difficult to continuously weave functional fibers containing light-emitting devices using conventional textile technologies. To address this issue, we introduced fibrous modules that can be assembled like LEGO blocks to realize textile displays. A unique feature of this work is that the light-emitting pixels are generated through a simple contact between modular electrochemiluminescent (ECL) fibers. Each fiber is composed of a single metallic wire coated with a gel-type ECL electrolyte that is formed by using a simple dip-coating method in ambient air. The sticky nature of the gel electrolyte enables the construction of light-emitting pixels through the simple physical contact of two or more fiber modules without the need for external pressure or heating. The diversity of this technology offers in terms of fibrous module arrangements and assembly can provide various options for designing the geometries of light-emitting pixels. We have implemented this technique to demonstrate not only a 1 × 1 pixel but also 3 × 3 pixels with an irregular shape. These results demonstrate that the unique strategy for display devices developed in this work provides a feasible approach for various electronic and optical textile applications.

Facile fabrication of gas sensors based on molybdenum disulfide nanosheets and carbon nanotubes by self-assembly.

The rising importance of gas detection has prompted rigorous research on flexible and transparent high-performance gas sensors. We demonstrated a sensor for NO2 detection at room temperature, in which our device was fabricated via screen printing on a flexible substrate, and MoS2 and single-walled carbon nanotube (SWCNT) were coated on a specific area by the self-assembly method. This fabrication process is rapid, facile, and cost-effective. The proposed sensor enables precise and stable NO2 gas sensing from 50 ppb to 100 ppm. This method should also be applicable to the selective detection of other gases.

One-STAGE Tip Method for TMT-Based Proteomic Analysis of a Minimal Amount of Cells.

Liquid chromatography-tandem mass spectrometry (LC-MS)-based profiling of proteomes with isobaric tag labeling from low-quantity biological and clinical samples, including needle-core biopsies and laser capture microdissection, has been challenging due to the limited amount and sample loss during preparation. To address this problem, we developed OnM (On-Column from Myers et al. and mPOP)-modified on-column method combining freeze-thaw lysis of mPOP with isobaric tag labeling of On-Column method to minimize sample loss. OnM is a method that processes the sample in one-STAGE tip from cell lysis to tandem mass tag (TMT) labeling without any transfer of the sample. In terms of protein coverage, cellular components, and TMT labeling efficiency, the modified On-Column (or OnM) displayed similar performance to the results from Myers et al. To evaluate the lower-limit processing capability of OnM, we utilized OnM for multiplexing and were able to quantify 301 proteins in a TMT 9-plex with 50 cells per channel. We optimized the method as low as 5 cells per channel in which we identified 51 quantifiable proteins. OnM method is a low-input proteomics method widely applicable and capable of identifying and quantifying proteomes from limited samples, with tools that are readily available in a majority of proteomic laboratories.

Water Washable and Flexible Light-Emitting Fibers Based on Electrochemiluminescent Gels.

Herein, a new concept of device architecture to fabricate fibrous light-emitting devices is demonstrated based on an electrochemiluminescence (ECL) material for an electronic textile system. A unique feature of this work is that instead of conventional semiconductor materials, such as organics, perovskites, and quantum dots for fibrous light emitting devices, a solid-state ECL electrolyte gel is employed as a light-emitting layer. The solid-state ECL gel is prepared from a precursor solution composed of matrix polymer, ionic liquid, and ECL luminophore. From this, we successfully realize light-emitting fibers through a simple and cost-effective single-step dip-coating method in ambient air, without complicated multistep vacuum processes. The resulting fiber devices reliably operated under applied AC bias of ±2.5 V and showed luminance of 47 cd m-2. More importantly, the light-emitting fibers exhibited outstanding water resistance without any passivation layers, owing to the water immiscible and hydrophobic nature of the ECL gel. In addition, because of their simple structure, the fiber devices can be easily deformed and woven together with commercial knitwear by hand. Therefore, these results suggest a promising strategy for the development of practical fiber displays and contribute to progress in electronic textile technology.

Impact of idiopathic pulmonary fibrosis on clinical outcomes of lung cancer patients.

The clinical characteristics of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) differ from those of lung cancer in patients without IPF. Thus, we aimed to evaluate the impact of IPF on the clinical course of patients with lung cancer. Clinical data of IPF patients with lung cancer (n = 122) were compared with those of patients with lung cancer without IPF (n = 488) matched by age, sex, histopathology, stage, and date of diagnosis of lung cancer. The median follow-up period after diagnosis of lung cancer was 16 months. Among patients with IPF, the mean age was 68 years, 95.9% were male, 93.2% were ever-smokers, and squamous cell carcinoma was the most common cancer type (48.4%). The IPF group had poorer lung function and lower lobe predominance of lung cancer than the no-IPF group. The IPF group showed a poorer prognosis than the no-IPF group (5-year survival rate: 14.5% vs. 30.1%, respectively; P < 0.001), even after adjusting for lung function and regardless of the treatment method. Among patients with IPF, 16.8% experienced acute exacerbation within 1 month after treatment of lung cancer. The treatment outcome of patients with lung cancer and IPF was generally unfavorable, and acute exacerbation triggered by treatment frequently occurred.

Electrochemiluminescent Transistors: A New Strategy toward Light-Emitting Switching Devices.

Light-emitting transistors (LETs) have attracted a significant amount of interest as multifunctional building blocks for next-generation electronics and optoelectronic devices. However, it is challenging to obtain LETs with a high carrier mobility and uniform light-emission because the semiconductor channel should provide both the electrical charge transport and optical light-emission, and typical emissive semiconductors have low, imbalanced carrier mobilities. In this work, a novel device platform that adapts the electrochemiluminescence (ECL) principle in LETs, referred to as an ECL transistor (ECLT) is proposed. ECL is a light-emission phenomenon from electrochemically excited luminophores generated by redox reactions. A solid-state ECL electrolyte consisting of a network-forming polymer, ionic liquid, luminophore, and co-reactant is employed as the light-emitting gate insulator of the ECLT. Based on this construction, high-performance LETs that make use of various conventional non-emissive semiconductors (e.g., poly(3-hexylthiophene), zinc oxide, and reduced graphene oxide) are successfully demonstrated. All the devices exhibit a high mobility (0.9-10 cm2 V-1 s-1 ) and a uniform light-emission. This innovative approach demonstrates a novel LET platform and provides a promising pathway to achieve significant breakthroughs to develop electronic circuits and optoelectronic applications.

Flexible hybrid photodetector based on silver sulfide nanoparticles and multi-walled carbon nanotubes.

Herein, we reported a wearable photodetector based on hybrid nanocomposites, such as carbon materials and biocompatible semiconductor nanocrystals (NCs), exhibiting excellent photoresponsivity and superior durability. Currently, semiconductor nanocrystal quantum dots (QDs) containing heavy metals, such as lead or cadmium (in the form of lead sulfide (PbS) and cadmium sulfide (CdS)), are known to display excellent detection properties and are thus widely employed in the fabrication of photodetectors. However, the toxic properties of these heavy metals are well known. Hence, in spite of their enormous potential, the QDs based on these heavy metals are not generally preferred in biological or biomedical applications. These limitations, though, can be overcome by the judicious choice of alternate materials such as silver sulfide (Ag2S) NCs, which are biocompatible and exhibit multiple excitons in Ag2S QDs. The other chosen component is a carbon-based material, such as the multi-walled carbon nanotube (MWCNT), which is preferred primarily due to its strong and superior mechanical durability. In this study, a hybrid nanocomposite film was synthesized from Ag2S NCs and MWCNTs by a simple one-step fabrication process using ultrasonic irradiation. Additionally, this method did not involve any chemical functionalization or post-processing step. The size of Ag2S NCs in the hybrid film was controlled by the irradiation time and the power of the ultrasonic radiation. Further, appropriate composition ratio of the hybrid composite was optimized to balance the photo-response and mechanical durability of the photodetector. Thus, using this synthetic method, an excellent photoresponsivity property of the device was demonstrated for a near-infrared (NIR) light source with various light wavelengths. Furthermore, no visible change in photoresponsivity was observed for bending motions up to 105 cycles and for a range of angles (0-60°). This novel method provides an eco-friendly alternative to existing functional composites containing toxic heavy metals and is a promising approach for the development of wearable optoelectronic devices.

Naa20, the catalytic subunit of NatB complex, contributes to hepatocellular carcinoma by regulating the LKB1-AMPK-mTOR axis.

N-α-acetyltransferase 20 (Naa20), which is a catalytic subunit of the N-terminal acetyltransferase B (NatB) complex, has recently been reported to be implicated in hepatocellular carcinoma (HCC) progression and autophagy, but the underlying mechanism remains unclear. Here, we report that based on bioinformatic analysis of Gene Expression Omnibus and The Cancer Genome Atlas data sets, Naa20 expression is much higher in HCC tumors than in normal tissues, promoting oncogenic properties in HCC cells. Mechanistically, Naa20 inhibits the activity of AMP-activated protein kinase (AMPK) to promote the mammalian target of rapamycin signaling pathway, which contributes to cell proliferation, as well as autophagy, through its N-terminal acetyltransferase (NAT) activity. We further show that liver kinase B1 (LKB1), a major regulator of AMPK activity, can be N-terminally acetylated by NatB in vitro, but also probably by NatB and/or other members of the NAT family in vivo, which may have a negative effect on AMPK activity through downregulation of LKB1 phosphorylation at S428. Indeed, p-LKB1 (S428) and p-AMPK levels are enhanced in Naa20-deficient cells, as well as in cells expressing the nonacetylated LKB1-MPE mutant; moreover, importantly, LKB1 deficiency reverses the molecular and cellular events driven by Naa20 knockdown. Taken together, our findings suggest that N-terminal acetylation of LKB1 by Naa20 may inhibit the LKB1-AMPK signaling pathway, which contributes to tumorigenesis and autophagy in HCC.