Soluble Programmed Cell Death Ligand-1 (sPD-L1) Levels in Various Cancer Types and Normal Populations.

BACKGROUND: To date, PD-L1 expression in tumor tissue, assessed by immunohistochemical stain, is clinically applicable as a predictive companion biomarker for PD-1/PD-L1 inhibitor which has been highlighted over the past several years. Before blood-based sPD-L1 enters clinical use, it is critical to establish the reference range. This study was designed to investigate soluble sPD-L1 levels in various cancer patients and normal population. METHODS: For the detection of sPD-L1, 4 cancer groups (hepatocellular carcinoma, lung cancer, bladder cancer, gastric cancer) and healthy volunteers' samples were analyzed using an ELISA kit. Using a receiver operating characteristic curve, optimal sPD-L1 cutoff levels were determined. RESULTS: The mean serum sPD-L1 level of the normal population was 59.97 pg/mL (range; 23.780 - 115.2 pg/mL). In various cancer types, serum sPD-L1 levels ranged from 38.696 pg/mL to 228.77 pg/mL, and cutoff values under AUC ranged from 60.307 pg/mL to 64.371 pg/mL. CONCLUSIONS: sPD-L1 can be used as a screening biomarker in various cancer patients referring to optimal cutoff levels suggested.

Experimental test of Babinet's principle in matter-wave diffraction.

We report on an experimental test of Babinet's principle in quantum reflection of an atom beam from diffraction gratings. The He beam is reflected and diffracted from a square-wave grating at near grazing-incidence conditions. According to Babinet's principle the diffraction peak intensities (except for the specular-reflected beam) are expected to be identical for any pair of gratings of complementary geometry. We observe conditions where Babinet's principle holds and also where it fails. Our data indicate breakdown conditions when either the incident or a diffracted beam propagates close to the grating surface. At these conditions, the incident or the diffracted He beam is strongly affected by the dispersive interaction between the atoms and the grating surface. Babinet's principle is also found to break down, when the complementary grating pair shows a large asymmetry in the strip widths. For very small strip widths, edge diffraction from half planes becomes dominant, whereas for the complementary wide strips the atom-surface interactions leads to a strong reduction of all non-specular diffraction peak intensities.

Hygroscopic Micro/Nanolenses along Carbon Nanotube Ion Channels.

Nanolenses of alkali metal halides can be a unique optical element due to their hygroscopicity, optical transparency, and high mobility of constituent ions. It has been challenging, however, to form and place such lenses in a controlled manner. Here, we report micro/nanolenses of various alkali metal halides arranged as a one-dimensional (1D) array, using the exterior of single-walled carbon nanotubes (SWNTs) as a template for forming the lenses. Applying an electrical bias to an aqueous solution of alkali metal halides placed at the end of an SWNT array causes ionic transport along the exterior of SWNTs and the subsequent formation of salt micro/nanocrystals. The crystals serve as micro/nanolenses that optically visualize individual SWNTs and amplify their Raman scattering by orders of magnitude. Molecules dissolved in the ionic solution can be electrokinetically transported along the nanotubes, captured within the lenses, and analyzed by Raman spectroscopy, which we demonstrate by detecting ∼12 attomoles of glucose and 2 femtomoles of urea. The hygroscopic salt nanolenses are robust under various ambient conditions indefinitely, by transitioning to liquid droplets above their deliquescence relative humidity, yet can be removed nondestructively by water. Our approach could have broad implications in the optical visualization of 1D nanostructures, molecular transport or chemical reactions in 1D space, and molecular spectroscopy in salty environments.

Relationship between calf muscle cross-sectional area and ankle fracture.

BACKGROUND: Whether calf muscles and peroneal muscles have a role in the occurrence of an ankle fractures remains unclear. This study aimed to quantify the calf muscle mass and peroneal muscle mass in patients with an ankle fracture and in controls, then to analyze them together with demographic factors to identify the effects of the regional muscles on the risk of developing ankle fracture. METHODS: A total of 101 ankles with computed tomography (CT) images were retrospectively reviewed. Of them, 51 ankles showed fractures (all unilateral) and 50 ankles, in controls who underwent CT for screening the other diseases, were clinically diagnosed with simple contusion. The cross-sectional areas (CSA) of the calf muscles and the peroneal muscles were measured at approximately 6 cm above the Achilles myotendinous junction in the axial plane of ankle CT. These parameters were compared between the two groups and analyzed with respect to age, sex, body mass index (BMI), laterality, and bone attenuations of the ankle. RESULTS: The demographic factors, including bone attenuation of the ankle showed no significant association with ankle fracture. The ratio of the CSA of the peroneal muscle group to the CSA of the entire calf muscle group was smaller in patients with an fracture (0.12 ± 0.03) than in controls (0.14 ± 0.02) (p = 0.027). The odds ratio for the effect of the calf muscle CSA on the risk of developing ankle fractures was 1.38 (95% confidence interval 1.12-1.69, p = 0.003), whereas that for the effect of peroneal muscle CSA on the risk of developing ankle fractures was 0.18 (95% confidence interval 0.05 to 0.66, p = 0.010). CONCLUSION: The ratio of the peroneal muscle CSA to the entire calf muscle CSA was negatively related to the occurrence of ankle fractures in this study. Further prospective studies on whether peroneal muscle-strengthening exercise are effective in preventing ankle fractures may be needed. LEVEL OF EVIDENCE: III, case-control study.

Interaction between the tumor microenvironment and resection margin in different gross types of hepatocellular carcinoma.

BACKGROUND AND AIM: There is no consensus regarding the safe resection margin in hepatocellular carcinoma (HCC). Several studies reported that different gross types require different resection margins. We investigated the changes in the tumor microenvironment (TME) in different gross types of HCC. METHODS: We selected tumor tissue and normal tissue 1 and 2 cm away from the HCC. We analyzed the expression status of TME genes and the correlation between TME genes and the effective resection margin. We further divided the patients into two groups: group 1 included expanding and vaguely nodular types, whereas group 2 included nodular with perinodular extension, multinodular confluent, and infiltrative types. RESULTS: Group 2 showed 27% and 45% 5-year disease-free survival (DFS) and overall survival (OS) rates, respectively. Group 2 was a significant prognostic factor for DFS and OS. In cases with a resection margin of less than 1 cm or more than 2 cm, there were no differences in recurrence and survival rate between the two groups. Group 1 patients who had a resection margin that ranged from 1 to 2 cm showed significantly better DFS and OS rates. ß-Catenin and matrix metalloproteinase 9 expression was significantly decreased and that of E-cadherin was significantly increased according to the resection margin in group 1. CONCLUSIONS: Patients with expanding and vaguely nodular HCC may safely undergo surgical resection with a narrow resection margin, and patients with the other gross types must undergo surgical resection with more than a 2-cm resection margin because of their TME conditions.

Matter-Wave Diffraction from a Periodic Array of Half Planes.

We report on reflection and diffraction of beams of He and D_{2} from square-wave gratings of a 400-µm period and strip widths ranging from 10 to 200 µm at grazing-incidence conditions. In each case we observe fully resolved matter-wave diffraction patterns including the specular reflection and diffracted beams up to the second diffraction order. With decreasing strip width, the observed diffraction efficiencies exhibit a transformation from the known regime of quantum reflection from the grating strips to the regime of edge diffraction from a half-plane array. The latter is described by a single-parameter model developed previously to describe phenomena as diverse as quantum billiards, scattering of radio waves in urban areas, and reflection of matter waves from microstructures. Our data provide experimental confirmation of the widespread model. Moreover, our results demonstrate that neither classical reflection nor quantum reflection are essential for reflective diffraction of matter waves from a structured solid, but it can result exclusively from half-plane edge diffraction.

Effects of Lysobacter antibioticus HS124, an effective biocontrol agent against Fusarium graminearum, on crown rot disease and growth promotion of wheat.

Lysobacter antibioticus HS124 inhibited mycelial growth of Fusarium graminearum (74.66%) under the dual culture method. Microscopic investigation clearly showed that amendment with different concentrations (10%, 30%, and 50%) of HS124 bacterial culture filtrate on potato dextrose agar plates caused abnormal hyphal structures, including swelling and distortion. Its inhibition toward mycelial growth of F. graminearum was increased with increasing concentration of n-butanol crude extract of HS124. The highest inhibition (43.14%) was detected at a crude concentration of 10 mg/disc, whereas the lowest inhibition (21.57%) was observed at 2 mg/disc. Although mycelial growth of F. graminearum was promoted by volatile organic compounds (VOCs) produced by HS124 as compared with the control, these VOCs clearly decreased fungal pigmentation resulting in a reduction of fungal sporulation. Microscopic investigation revealed hyphal deformation of F. graminearum due to VOCs. These compounds also had a negative effect on spore germination of F. graminearum. In vivo evaluations demonstrated that HS124 inoculation of wheat plants reduced crown rot disease incidence by 73.70% as compared with the control. HS124 inoculation of wheat plants also promoted most of the growth characteristics compared with the control or fungicide-treated plants. Our results provide strong evidence that HS124 could control F. graminearum infections and promote growth of wheat plants as part of management strategies for crown rot disease.

An Annulative Synthetic Strategy for Building Triphenylene Frameworks by Multiple C-H Bond Activations.

C-H activation is a versatile tool for appending aryl groups to aromatic systems. However, heavy demands on multiple catalytic cycle operations and site-selectivity have limited its use for graphene segment synthesis. A Pd-catal- yzed one-step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2- or 4-fold C-H arylation of unactivated benzene derivatives. A Pd2 (dibenzylideneacetone)3 catalytic system, using cyclic diaryliodonium salts as π-extending agents, leads to site-selective inter- and intramolecular tandem arylation sequences. Moreover, N-substituted triphenylenes are applied to a field-effect transistor sensor for rapid, sensitive, and reversible alcohol vapor detection.

Ascertaining injury risk issues through big data analysis: text-mining based analysis of national emergency response data.

Objectives: Injury prevention can be achieved through various interventions, but it faces challenges due to its comprehensive nature and susceptibility to external environmental factors, making it difficult to detect risk signals. Moreover, the reliance on standardized systems leads to the construction and statistical analysis of numerous injury surveillance data, resulting in significant temporal delays before being utilized in policy formulation. This study was conducted to quickly identify substantive injury risk problems by employing text mining analysis on national emergency response data, which have been underutilized so far. Methods: With emerging issue and topic analyses, commonly used in science and technology, we detected problematic situations and signs by deriving injury keywords and analyzing time-series changes. Results: In total, 65 injury keywords were identified, categorized into hazardous, noteworthy, and diffusion accidents. Semantic network analysis on hazardous accident terms refined the injury risk issues. Conclusion: An increased risk of winter epidemic fractures due to extreme weather, self-harm due to depression (especially drug overdose and self-mutilation), and falls was observed in older adults. Thus, establishing effective injury prevention strategies through inter-ministerial and interagency cooperation is necessary.

Clinical and histological characteristics of melanocytic nevus in external auditory canals and auricles.

Nevi, which consist of nevus cells arising from external auditory canals (EACs) and auricles, are rare and their characteristics are not thoroughly understood. The purpose of this study was to analyze the clinicopathological characteristics of melanocytic nevus (MN) in EACs and auricles. Medical records were reviewed in 35 cases with junctional, compound and intradermal nevi treated in Ajou University Hospital, Korea between 2001 and 2011. Patient demographic, location, shape, and diameter of nevi, and pathologic results were analyzed according to the location, EACs (23 cases) and auricles (12 cases). Female predominance was noted in both EAC (60.9 %, 14 cases) and auricular (75 %, 9 cases) nevi. The mean age of EAC nevi (37.1 years) was younger than that of auricular nevi (42.2 years). The chief complaint was a symptomless mass in both groups, mostly in dome-like gross appearances. The mean diameter of EAC and auricular nevi was 9.6 (3-16) mm and 12.2 (3-25) mm, respectively. Histological findings chiefly presented intradermal nevi in EACs (78.3 %) and auricles (83.3 %) which showed preference to older patients, in contrast to the compound type. All nevi including five cases with skin grafts were completely excised without any recurrence within the follow-up period (average 5.3 months). A possible dysplastic nevus was detected in only one case. All MNs in EACs or auricles reveal similar characteristics. Early and complete excision is recommended to avoid skin graft, functional problems, and the risk of malignant melanoma.

Interference micro/nanolenses of salts for local modulation of Raman scattering.

Micro/nanolenses play a crucial role in optics and spectroscopy, but the effect of interference patterns within each lens has been largely unexplored. Herein, we investigate modulation of Raman scattering by the interference within a single micro/nanolens of a hygroscopic salt. Lenses having two different diameter (d) ranges, d > 2 µm and d ∼1 µm, are placed on a silicon substrate, followed by collection of a Raman intensity map of the silicon peak. Lenses with d > 2 µm show dark and bright circular fringes in the Raman map, resembling the Newton's rings formed by optical interference. In the smaller lenses (d ∼1 µm), the map yields only a single peak at the center, representing either an intensity maximum or minimum. In both diameter ranges, whether the Raman intensity is enhanced or suppressed is determined by interference conditions, such as wavelength of the excitation laser or thickness of the SiO2 layer. The interference in salt micro/nanolenses finds applications in local modulation of Raman scattering of a nanoscale object, as demonstrated in individual single-walled carbon nanotubes decorated with the salt lenses.

Cost-effectiveness of rhythm control strategy: Ablation versus antiarrhythmic drugs for treating atrial fibrillation in Korea based on real-world data.

Background: Ablation-based treatment has emerged as an alternative rhythm control strategy for symptomatic atrial fibrillation (AF). Recent studies have demonstrated the cost-effectiveness of ablation compared with medical therapy in various circumstances. We assessed the economic comparison between ablation and medical therapy based on a nationwide real-world population. Methods and findings: For 192,345 patients with new-onset AF (age ≥ 18 years) identified between August 2015 and July 2018 from the Korean Health Insurance Review and Assessment Service (HIRA) database, medical resource use data were collected to compare AF patients that underwent ablation (N = 2,131) and those administered antiarrhythmic drugs (N = 8,048). Subsequently, a Markov chain Monte Carlo model was built. The patients had at least one risk factor for stroke, and the base-case used a 20-year time horizon, discounting at 4.5% annually. Transition probabilities and costs were estimated using the present data, and utilities were derived from literature review. The costs were converted to US $ (2019). Sensitivity analyses were performed using probabilistic and deterministic methods. The net costs and quality-adjusted life years (QALY) for antiarrhythmic drugs and ablation treatments were $37,421 and 8.8 QALYs and $39,820 and 9.3 QALYs, respectively. Compared with antiarrhythmic drugs, incremental cost-effectiveness ratio of ablation was $4,739/QALY, which is lower than the willingness-to-pay (WTP) threshold of $32,000/QALY. Conclusion: In symptomatic AF patients with a stroke risk under the age of 75 years, ablation-based rhythm control is potentially a more economically attractive option compared with antiarrhythmic drug-based rhythm control in Korea.

Prevalence, incidence, and outcomes of hepatitis E virus coinfection in patients with chronic hepatitis C.

This study aimed to elucidate the anti-hepatitis E virus (HEV) immunoglobulin G (IgG) prevalence and incidence of seroconversion and seroreversion as well as its risk factors and to analyze the clinical outcomes of HEV and hepatitis C virus (HCV) coinfected patients compared to those of HCV-monoinfected patients. We prospectively enrolled 502 viremic HCV patients with paired plasma samples (at intervals of ≥ 12 months) from 5 tertiary hospitals. Anti-HEV IgG positivity was tested using the Wantai ELISA kit in all paired samples. Mean age was 58.2 ± 11.5 years old, 48.2% were male, 29.9% of patients had liver cirrhosis, and 9.4% of patients were diagnosed with hepatocellular carcinoma (HCC). The overall prevalence of anti-HEV IgG positivity at enrollment was 33.3%, with a higher prevalence in males and increasing prevalence according to the subject's age. During the 916.4 person-year, the HEV incidence rate was 0.98/100 person-years (9/335, 2.7%). Hepatic decompensation or liver-related mortality was not observed. There were six seroreversion cases among 172 anti-HEV-positive patients (1.22/100 person-years). In conclusion, approximately one-third of the adult Korean chronic HCV patients were anti-HEV IgG positive. The HEV incidence rate was 1 in 100 persons per year, without adverse hepatic outcomes or mortality.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Synthesis of fluorene-based semiconducting copolymers for organic solar cells.

Semiconducting polymers composed of 2,2'-(9,9-dioctyl-9H-fluorene-2,7-diyl)dithiophenes (F8T2s) and (2E,2'E)-3,3'-(2,5-bis(octyloxy)-1,4-phenylene) bis(2-(5-bromothiophene-2-yl)acrylonitrile)s (OPTANs) have been synthesized through Pd(O)-catalyzed Suzuki coupling polymerization by controlling the monomer ratio. The synthesized polymers were confirmed to exhibit good solubility in common solvents, simple processability, and thermal stability up to 350 degrees C. The highest occupied molecular orbitals (HOMOs), lowest unoccupied molecular orbitals (LUMOs), and optical band-gap energies were determined using cyclic voltammetry (CV) and UV-visible spectrometry. The synthesized polymers showed their maximum absorption and edge at around 520 and 650 nm, respectively. The optical band-gap energies of the polymers were determined to be 1.89 eV. Bulk heterojunction organic solar cells were fabricated using the conjugated polymer as the electron donor, and 6,6-phenyl C61-butyric acid methylester (PC61BM) or 6,6-phenyl C71-butyric acid methylester (PC71BM) as the electron acceptor. The power conversion efficiencies (PCEs) of the solar cells based on polymer:PC71BM (1:1) and polymer:PC71BM (1:2) were 0.68% and 1.22%, respectively, under air mass 1.5 global (AM 1.5 G) illumination at 100 mW/cm2.

Cost-effectiveness of Direct Oral Anticoagulant vs. Warfarin Among Atrial Fibrillation Patients With Intermediate Stroke Risk.

Background: Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data. Methods: We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained. Results: The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis. Conclusion: Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.

Changes in intrinsic functional brain connectivity related to occupational stress of firefighters.

Firefighters are exposed to physical and mental threats in the working environment that put them at risk for occupational stress and burnout. Stress responses can impact the functional interactions between brain regions involved in emotional and cognitive regulation. The objective of this study was to investigate brain functional connectivity (FC) related to occupational stress in firefighters. Male firefighters (n = 77) completed the Korean Occupational Stress Scale questionnaire on occupational stress and underwent brain magnetic resonance imaging. Seed-based FC analyses were conducted by setting core regions of the large-scale functional networks as seeds. Subsequent correlational analyses detected relationships between occupational stress scale scores and brain FC. The results showed that occupational stress was negatively correlated with FC between the central executive network (CEN)-related brain regions and seed regions of other networks. Additionally, occupational stress was negatively correlated with FC within the default mode network (DMN), but positively correlated with FC between the salience network (SN) and the DMN. Changes in FC in large-scale neural networks are likely involved in occupational stress responses. Taken together, these results suggest that proper management of occupational stress may help prevent the occurrence of clinical problems caused by changes in brain functional networks.

The effect of polycyclic aromatic hydrocarbons on changes in the brain structure of firefighters: An analysis using data from the Firefighters Research on Enhancement of Safety & Health study.

Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion of organic matter, and firefighters are highly exposed to these toxic compounds at fire sites. Exposure to PAHs can cause cognitive decline and neurodegeneration; however, to date, few studies have examined the potential effects of PAH exposure on structural changes in the brain. We aimed to investigate the association between the four types of PAH metabolites and the corresponding changes in neuroimaging markers based on smoking status and hypertension in male firefighters. For this, we utilized the 2-year follow-up data of 301 Korean male firefighters aged over 40 years. The concentrations of four PAH metabolites in urine were measured. Subcortical volume and cortical thickness were estimated using 3 T magnetic resonance imaging of the brain. A generalized linear model was used to investigate the effects of PAHs on changes in the subcortical volume and cortical thickness. We found an association between 1-hydroxyphenathrene (1-OHPHE) and 2-hydroxyfluorene (2-OHF) and changes in several brain regions in all the study participants. Individuals who had never smoked showed significantly thinner frontal (p < 0.001), parietal (p < 0.001), temporal (p < 0.001), and cingulate lobes (p < 0.001) with 1% increase each in the urinary concentration of 1-OHPHE. Hypertension interacted with the concentration of 1-OHPHE to reduce the volume of gray matter and cause cortical thinning in the frontal, parietal, and temporal lobes. Exposure to PAHs may reduce cortical thickness and subcortical volume, which are definitive markers of neurodegeneration. Notably, hypertension can accelerate the degenerative effects of PAHs.

Actuating compact wearable augmented reality devices by multifunctional artificial muscle.

An artificial muscle actuator resolves practical engineering problems in compact wearable devices, which are limited to conventional actuators such as electromagnetic actuators. Abstracting the fundamental advantages of an artificial muscle actuator provides a small-scale, high-power actuating system with a sensing capability for developing varifocal augmented reality glasses and naturally fit haptic gloves. Here, we design a shape memory alloy-based lightweight and high-power artificial muscle actuator, the so-called compliant amplified shape memory alloy actuator. Despite its light weight (0.22 g), the actuator has a high power density of 1.7 kW/kg, an actuation strain of 300% under 80 g of external payload. We show how the actuator enables image depth control and an immersive tactile response in the form of augmented reality glasses and two-way communication haptic gloves whose thin form factor and high power density can hardly be achieved by conventional actuators.

Alkalide-Assisted Direct Electron Injection for the Noninvasive n-Type Doping of Graphene.

Although the doping of graphene grown by chemical vapor deposition is crucial in graphene-based electronics, noninvasive methods of n-type doping have not been widely investigated in comparison with p-type doping methods. We developed a convenient and robust method for the noninvasive n-type doping of graphene, wherein electrons are directly injected from sodium anions into the graphene. This method involves immersing the graphene in solutions of [K(15-crown-5)2]Na prepared by dissolving a sodium-potassium (NaK) alloy in a 15-crown-5 solution. The n-type doping of the graphene was confirmed by downshifted G and 2D bands in Raman spectra and by the Dirac point shifting to a negative voltage. The electron-injected graphene showed no sign of structural damage, exhibited higher carrier mobilities than that of pristine graphene, and remained n-doped for over a month of storage in air. In addition, we demonstrated that electron injection enhances noncovalent interactions between graphene and metallomacrocycle molecules without requiring a linker, as used in previous studies, suggesting several potential applications of the method in modifying graphene with various functionalities.