Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer.

The drivers of immune evasion are not entirely clear, limiting the success of cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate immune evasion in high-grade serous tubo-ovarian cancer. To this end, we first mapped the spatial organization of high-grade serous tubo-ovarian cancer by profiling more than 2.5 million cells in situ in 130 tumors from 94 patients. This revealed a malignant cell state that reflects tumor genetics and is predictive of T cell and natural killer cell infiltration levels and response to immune checkpoint blockade. We then performed Perturb-seq screens and identified genetic perturbations-including knockout of PTPN1 and ACTR8-that trigger this malignant cell state. Finally, we show that these perturbations, as well as a PTPN1/PTPN2 inhibitor, sensitize ovarian cancer cells to T cell and natural killer cell cytotoxicity, as predicted. This study thus identifies ways to study and target immune evasion by linking genetic variation, cell-state regulators and spatial biology.

Flat-surface-assisted and self-regulated oxidation resistance of Cu(111).

Oxidation can deteriorate the properties of copper that are critical for its use, particularly in the semiconductor industry and electro-optics applications1-7. This has prompted numerous studies exploring copper oxidation and possible passivation strategies8. In situ observations have, for example, shown that oxidation involves stepped surfaces: Cu2O growth occurs on flat surfaces as a result of Cu adatoms detaching from steps and diffusing across terraces9-11. But even though this mechanism explains why single-crystalline copper is more resistant to oxidation than polycrystalline copper, the fact that flat copper surfaces can be free of oxidation has not been explored further. Here we report the fabrication of copper thin films that are semi-permanently oxidation resistant because they consist of flat surfaces with only occasional mono-atomic steps. First-principles calculations confirm that mono-atomic step edges are as impervious to oxygen as flat surfaces and that surface adsorption of O atoms is suppressed once an oxygen face-centred cubic (fcc) surface site coverage of 50% has been reached. These combined effects explain the exceptional oxidation resistance of ultraflat Cu surfaces.

Dimensionality Engineering of Magnetic Anisotropy from the Anomalous Hall Effect in Synthetic SrRuO3 Crystals.

Magnetic anisotropy in atomically thin correlated heterostructures is essential for exploring quantum magnetic phases for next-generation spintronics. Whereas previous studies have mostly focused on van der Waals systems, here we investigate the impact of dimensionality of epitaxially grown correlated oxides down to the monolayer limit on structural, magnetic, and orbital anisotropies. By designing oxide superlattices with a correlated ferromagnetic SrRuO3 and nonmagnetic SrTiO3 layers, we observed modulated ferromagnetic behavior with the change of the SrRuO3 thickness. Especially, for three-unit-cell-thick layers, we observe a significant 1500% improvement of the coercive field in the anomalous Hall effect, which cannot be solely attributed to the dimensional crossover in ferromagnetism. The atomic-scale heterostructures further reveal the systematic modulation of anisotropy for the lattice structure and orbital hybridization, explaining the enhanced magnetic anisotropy. Our findings provide valuable insights into engineering the anisotropic hybridization of synthetic magnetic crystals, offering a tunable spin order for various applications.

Effect of tryptophan position and lysine/arginine substitution in antimicrobial peptides on antifungal action.

Every year, the overprescription, misuse, and improper disposal of antibiotics have led to the rampant development of drug-resistant pathogens and, in turn, a significant increase in the number of patients who die of drug-resistant fungal infections. Recently, researchers have begun investigating the use of antimicrobial peptides (AMPs) as next-generation antifungal agents to inhibit the growth of drug-resistant fungi. The antifungal activity of alpha-helical peptides designed using the cationic amino acids containing lysine and arginine and the hydrophobic amino acids containing isoleucine and tryptophan were evaluated using 10 yeast and mold fungi. Among these peptides, WIK-14, which is composed of a 14-mer with tryptophan sequences at the amino terminus, showed the best antifungal activity via transient pore formation and ROS generation. In addition, the in vivo antifungal effects of WIK-14 were investigated in a mouse model infected with drug-resistant Candida albicans. The results demonstrate the potential of AMPs as antifungal agents.

Optoelectronic Synapse Based on 2D Electron Gas in Stoichiometry-Controlled Oxide Heterostructures.

Emulating synaptic functionalities in optoelectronic devices is significant in developing artificial visual-perception systems and neuromorphic photonic computing. Persistent photoconductivity (PPC) in metal oxides provides a facile way to realize the optoelectronic synaptic devices, but the PPC performance is often limited due to the oxygen vacancy defects that release excess conduction electrons without external stimuli. Herein, a high-performance optoelectronic synapse based on the stoichiometry-controlled LaAlO3/SrTiO3 (LAO/STO) heterostructure is developed. By increasing La/Al ratio up to 1.057:1, the PPC is effectively enhanced but suppressed the background conductivity at the LAO/STO interface, achieving strong synaptic behaviors. The spectral noise analyses reveal that the synaptic behaviors are attributed to the cation-related point defects and their charge compensation mechanism near the LAO/STO interface. The short-term and long-term plasticity is demonstrated, including the paired-pulse facilitation, in the La-rich LAO/STO device upon exposure to UV light pulses. As proof of concepts, two essential synaptic functionalities, the pulse-number-dependent plasticity and the self-noise cancellation, are emulated using the 5 × 5 array of La-rich LAO/STO synapses. Beyond the typical oxygen deficiency control, the results show how harnessing the cation stoichiometry can be used to design oxide heterostructures for advanced optoelectronic synapses and neuromorphic applications.

Memristive Artificial Synapses Based on Brownmillerite for Endurable Weight Modulation.

Exploring a computing paradigm that blends memory and computation functions is essential for artificial synapses. While memristors for artificial synapses are widely studied due to their energy-efficient structures, random filament conduction in general memristors makes them less preferred for endurability in long-term synaptic modulation. Herein, the topotactic phase transition (TPT) in brownmillerite-phased (110)-SrCoO2.5 (SCO2.5) is harnessed to enhance the reversibility of oxygen ion migration through 1-D oxygen vacancy channels. By employing a heteroepitaxial structured 2-terminal configuration of Au/SCO2.5/SrRuO3/SrTiO3, the brownmillerite SCO2.5-based synapse artificial synapses are exploited. Demonstration of the TPT behavior is corroborated by comparing oxygen migration energy by density-functional theory calculations and experimental results, and by monitoring the voltage pulse-induced peak shift in the Raman spectra of SCO2.5. With the voltage pulse-driven TPT behaviors, it is reliably characterized by linear, symmetric, and endurable long-term potentiation and depression performances. Notably, the durability of the TPT-based weight control mechanism is demonstrated by achieving consistent and noise-free weight updates over 32 000 iterations across 640 cycles. Furthermore, learning performances based on deep neural networks and convolutional neural networks on various image datasets yielded very high recognition accuracy. The work offers valuable insights into designing memristive synapses that enable reliable weight updates in neural networks.

Universal Platform for Robust Dual-Atom Doped 2D Catalysts with Superior Hydrogen Evolution in Wide pH Media.

Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2. First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.

First Report of Fruit Scab Caused by Alternaria alternata on Actinidia chinensis in Korea.

Kiwi (Actinidia chinesis) is an economically important fruit in Korea, with 1,300 ha cultivated and a production of approximately 25,000 tons per year (Kim and Koh, 2018; Kim and Choi, 2023). In late June 2020, fruit scab symptoms were observed on A. chinensis var. rufopulpa in an orchard in Suncheon, Korea. The incidence of scab symptoms among 20-year-old trees was over 75%, primarily superficial, but rendered the fruit less marketable. In the initial stages of the disease, small, light-brown, circular, and oval spots were formed. As the superficial spots expanded, they became cracked scabs measuring 1 to 7 cm with light edges at the later stages. To isolate the causal pathogen, two lesions were cut from two sections of symptomatic tissue, from each of seven fruits from seven trees. Lesions were surface-sterilized with 70% ethanol for 1 min and washed three times with sterilized distilled water (SDW). The sterilized pieces were placed on potato dextrose agar (PDA) and incubated in the dark at 25°C for one week. After subculturing on PDA, single-spore isolation produced 14 isolates: SYP-410 to 423). All 14 colonies appeared greyish-green and cottony on PDA after 7 d. Conidia were pale brown, ellipsoid to obclavate, with ornamented walls, 1 to 6 transverse and 0 to 3 vertical septa, and length × width of 21.5 to 53.4 × 7.3 to 19.2 µm (avg. 33.0 × 12.0 µm, n = 100). Their morphological characteristics were consistent with Alternaria spp. (van der Waals et al. 2011; Woudenberg et al. 2015). We randomly selected three isolates from the morphologically similar cultures and named them SYP-412 to 414 for further investigation. The ITS (GenBank accession nos.: OR901850 to 52), gapdh (OR924309 to 11), tef1 (OR924312 to 14), rpb2 (OR924315 to 17), Alt a1 (OR924318 to 20), endoPG (OR924321 to 23), and OPA10-2 (OR924324 to 26) sequences from SYP-412 to 414 had a 100% (515 bp/515 bp), 100% (578/578), 100% (240/240), 100% (724/724), 95.55% (451/472), 99.33% (445/448), and 100% (634/634) identity with that of type strain A. alternata CBS 918.96 (AF347032, AY278809, KC584693, KC584435, AY563302, KP124026, and KP124633), respectively. Results from the maximum likelihood phylogenetic analysis, based on the seven concatenated gene sequences, placed the representative isolates in a clade with A. alternata. Pathogenicity of SYP-412 was tested using 12 surface-sterilized two-month-old kiwifruits on a 20-year-old trees. Six kiwifruits were spray-inoculated with 5 mL of a conidial suspension (1 × 106 conidia/ml) generated after culturing in PDA medium for 7 d, with or without wounding. Another six control fruits were inoculated with SDW with and without wounding. The inoculated kiwifruits were enclosed in plastic bags to maintain high humidity for one day. Scab symptoms were observed in both wounded and unwounded fruits six weeks after inoculation, but not in the control. The pathogenicity test was performed on a total of three separate trees twice. To satisfy Koch's postulates, A. alternata was re-isolated from all the symptomatic tissues and confirmed by analyzing the ITS and rpb2 genes. Although scab disease caused by A. tenuissima (now A. alternata) has been previously reported in kiwifruit of A. chinensis var. rufopulpa in China (Woudenberg et al. 2015; Ma et al., 2019), this is the first report of its occurrence on kiwifruit in Korea and will help in future detection and control.

13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

Rowhammer Attacks in Dynamic Random-Access Memory and Defense Methods.

This paper provides a comprehensive overview of the security vulnerability known as rowhammer in Dynamic Random-Access Memory (DRAM). While DRAM offers many desirable advantages, including low latency, high density, and cost-effectiveness, rowhammer vulnerability, first identified in 2014, poses a significant threat to computing systems. Rowhammer attacks involve repetitive access to specific DRAM rows, which can cause bit flips in neighboring rows, potentially compromising system credentials, integrity, and availability. The paper discusses the various stages of rowhammer attacks, explores existing attack techniques, and examines defense strategies. It also emphasizes the importance of understanding DRAM organization and the associated security challenges.

Reversible Photomodulation of Two-Dimensional Electron Gas in LaAlO3/SrTiO3 Heterostructures.

Long-lived photoinduced conductance changes in LaAlO3/SrTiO3 (LAO/STO) heterostructures enable their use in optoelectronic memory applications. However, it remains challenging to quench the persistent photoconductivity (PPC) instantly and reproducibly, which limits the reversible optoelectronic switching. Herein, we demonstrate a reversible photomodulation of two-dimensional electron gas (2DEG) in LAO/STO heterostructures with high reproducibility. By irradiating UV pulses, the 2DEG at the LAO/STO interface is gradually transformed to the PPC state. Notably, the PPC can be completely removed by water treatment when two key requirements are met: (1) the moderate oxygen deficiency in STO and (2) the minimal band edge fluctuation at the interface. Through our X-ray photoelectron spectroscopy and electrical noise analysis, we reveal that the reproducible change in the conductivity of 2DEG is directly attributed to the surface-driven electron relaxation in the STO. Our results provide a stepping-stone toward developing optically tunable memristive devices based on oxide 2DEG systems.

Effect of Torilis japonica Fruit Extract for Endothelium-Independent Vasorelaxation and Blood Pressure Lowering in Rats.

Torilis japonica (TJ) fruit, is a herb that is traditionally used for erectile dysfunction (ED). Given the shared mechanisms of ED and hypertension through vascular smooth muscle, we hypothesized that TJ would be effective in vasodilation and blood pressure reduction. This study confirmed the authenticity of TJ samples via DNA barcoding and quantified the main active compound, torilin, using HPLC. TJ was extracted with distilled water (TJW) and 50% ethanol (TJE), yielding torilin contents of 0.35 ± 0.01% and 2.84 ± 0.02%, respectively. Ex vivo tests on thoracic aortic rings from Sprague-Dawley rats showed that TJE (3-300 µg/mL) induced endothelium-independent, concentration-dependent vasodilation, unlike TJW. Torilin caused concentration-dependent relaxation with an EC50 of 210 ± 1.07 µM. TJE's effects were blocked by a voltage-dependent K+ channel blocker and alleviated contractions induced by CaCl2 and angiotensin II. TJE inhibited vascular contraction induced by phenylephrine or KCl via extracellular CaCl2 and enhanced inhibition with nifedipine, indicating involvement of voltage-dependent and receptor-operated Ca2+ channels. Oral administration of TJE (1000 mg/kg) significantly reduced blood pressure in spontaneously hypertensive rats. These findings suggest TJ extract's potential for hypertension treatment through vasorelaxant mechanisms, though further research is needed to confirm its efficacy and safety.

MoNOT3 Subunit Has Important Roles in Infection-Related Development and Stress Responses in Magnaporthe oryzae.

The multifunctional carbon catabolite repression negative on TATA-box-less complex (CCR4-NOT) is a multi-subunit complex present in all eukaryotes, including fungi. This complex plays an essential role in gene expression; however, a functional study of the CCR4-NOT complex in the rice blast fungus Magnaporthe oryzae has not been conducted. Seven genes encoding the putative CCR4-NOT complex were identified in the M. oryzae genome. Among these, a homologous gene, MoNOT3, was overexpressed during appressorium development in a previous study. Deletion of MoNOT3 in M. oryzae resulted in a significant reduction in hyphal growth, conidiation, abnormal septation in conidia, conidial germination, and appressorium formation compared to the wild-type. Transcriptional analyses suggest that the MoNOT3 gene affects conidiation and conidial morphology by regulating COS1 and COM1 in M. oryzae. Furthermore, Δmonot3 exhibited a lack of pathogenicity, both with and without wounding, which is attributable to deficiencies in the development of invasive growth in planta. This result was also observed in onion epidermal cells, which are non-host plants. In addition, the MoNOT3 gene was involved in cell wall stress responses and heat shock. Taken together, these observations suggest that the MoNOT3 gene is required for fungal infection-related cell development and stress responses in M. oryzae.

Effects of structural changes on antibacterial activity and cytotoxicity due to proline substitutions in chimeric peptide HnMc.

Owing to the rapidly increasing emergence of multidrug-resistant pathogens, antimicrobial peptides (AMPs) are being explored as next-generation antibiotics. However, AMPs present in nature are highly toxic and exhibit low antibacterial activity. Simple modifications, such as amino acid substitution, can enhance antimicrobial activity and cell selectivity. Herein, we show that HnMc-W, substituted by the Phe1Trp analog of HnMc, a chimeric peptide, resulted in membranolytic antibacterial action and enhanced salt tolerance, whereas HnMc-WP1 with one Ser9Pro substitution resulted in a proline-kink helical structure that increased salt-tolerant antibacterial effects and reduced cytotoxicity. In addition, the HnMc-WP2 peptide, designed with a PXXP motif, had a flexible central hinge in its α-helical structure due to the introduction of two Pro and two Gln (X positions, by deletion of two Gln at positions 16 and 17) residues instead of Ser at position. HnMc-WP2 exhibited excellent antibacterial effects without cytotoxicity in vitro. Moreover, its potent antibacterial activity was demonstrated in a drug-resistant Pseudomonas aeruginosa-infected mouse model in vivo. Our findings provide valuable information for the design of peptides with high antibacterial activity and cell selectivity.

Thermo-Responsive Nanocomposite Bioink with Growth-Factor Holding and its Application to Bone Regeneration.

Three-dimensional (3D) bioprinting, which is being increasingly used in tissue engineering, requires bioinks with tunable mechanical properties, biological activities, and mechanical strength for in vivo implantation. Herein, a growth-factor-holding poly(organophosphazene)-based thermo-responsive nanocomposite (TNC) bioink system is developed. The mechanical properties of the TNC bioink are easily controlled within a moderate temperature range (5-37 °C). During printing, the mechanical properties of the TNC bioink, which determine the 3D printing resolution, can be tuned by varying the temperature (15-30 °C). After printing, TNC bioink scaffolds exhibit maximum stiffness at 37 °C. Additionally, because of its shear-thinning and self-healing properties, TNC bioinks can be extruded smoothly, demonstrating good printing outcomes. TNC bioink loaded with bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta1 (TGF-ß1), key growth factors for osteogenesis, is used to print a scaffold that can stimulate biological activity. A biological scaffold printed using TNC bioink loaded with both growth factors and implanted on a rat calvarial defect model reveals significantly improved bone regenerative effects. The TNC bioink system is a promising next-generation bioink platform because its mechanical properties can be tuned easily for high-resolution 3D bioprinting with long-term stability and its growth-factor holding capability has strong clinical applicability.

Aberration-free warp projection on a horopter screen using freeform holographic optical elements.

A horopter screen has been popularly studied since its curvature reduces the parallax between two eyes and the immersive displays with a horopter-curved screen are regarded to provide vivid impression of depth and stereopsis. But, the projection on a horopter screen causes some practical problems that the image is hard to be focused on the entire screen and its magnification is partially different. An aberration-free warp projection has a great potential to solve these problems, which changes the optical path from an object plane to an image plane. Since the variation of the curvature is severe in the horopter screen, a freeform optical element is required for an aberration-free warp projection. In comparison with the traditional fabrication method, the hologram printer has the advantage of rapidly manufacturing free-form optical devices by recording the desired wavefront phase on the holographic medium. In this paper, for a given arbitrary horopter screen, the aberration-free warp projection is implemented with the freeform holographic optical elements (HOEs) fabricated by our tailor-made hologram printer. We experimentally demonstrate that the distortion and defocus aberration are effectively corrected.

Tensile strained direct bandgap GeSn microbridges enabled in GeSn-on-insulator substrates with residual tensile strain.

Despite having achieved drastically improved lasing characteristics by harnessing tensile strain, the current methods of introducing a sizable tensile strain into GeSn lasers require complex fabrication processes, thus reducing the viability of the lasers for practical applications. The geometric strain amplification is a simple technique that can concentrate residual and small tensile strain into localized and large tensile strain. However, the technique is not suitable for GeSn due to the intrinsic compressive strain introduced during the conventional epitaxial growth. In this Letter, we demonstrate the geometrical strain amplification in GeSn by employing a tensile strained GeSn-on-insulator (GeSnOI) substrate. This work offers exciting opportunities in developing practical wavelength-tunable lasers for realizing fully integrated photonic circuits.

Enhanced second-harmonic generation in strained germanium-on-insulator microdisks for integrated quantum photonic technologies.

Quantum photonic circuits have recently attracted much attention owing to the potential to achieve exceptional performance improvements over conventional classical electronic circuits. Second-order χ(2) nonlinear processes play an important role in the realization of several key quantum photonic components. However, owing to their centrosymmetric nature, CMOS-compatible materials including silicon (Si) and germanium (Ge) traditionally do not possess the χ(2) response. Recently, second-harmonic generation (SHG) that requires the χ(2) response was reported in Ge, but no attempts at enhancing the SHG signal have been conducted and proven experimentally. Herein, we demonstrate the effect of strain on SHG from Ge by depositing a silicon nitride (Si3N4) stressor layer on Ge-on-insulator (GOI) microdisks. This approach allows the deformation of the centrosymmetric unit cell structure of Ge, which can further enhance the χ(2) nonlinear susceptibility for SHG emission. The experimental observation of SHG under femtosecond optical pumping indicates a clear trend of enhancement in SHG signals with increasing strain. Such improvements boost conversion efficiencies by 300% when compared to the control counterpart. This technique paves the way toward realizing a CMOS-compatible material with nonlinear characteristics, presenting unforeseen opportunities for its integration in the semiconductor industry.

Gymnodinialimonas phycosphaerae sp. nov., a phycosphere bacterium isolated from Karlodinium veneficum.

A facultative anaerobic, Gram-negative, non-motile, rod-shaped bacterial strain, designated N5T, was obtained from the phycosphere microbiota of the marine planktonic dinoflagellate, Karlodinium veneficum. Strain N5T showed growth on marine agar at 25 °C, pH 7 and 1 % (w/v) NaCl and produced a yellow colour. According to a phylogenetic study based on 16S rRNA gene sequences, strain N5T has a lineage within the genus Gymnodinialimonas. The G+C content in the genome of strain N5T is 62.9 mol% with a total length of 4 324 088 bp. The NCBI Prokaryotic Genome Annotation Pipeline revealed that the N5T genome contained 4230 protein-coding genes and 48 RNA genes, including a 5S rRNA, 16S rRNA, 23S rRNA, 42 tRNA, and three ncRNAs. Genome-based calculations (genome-to-genome distance, average nucleotide identity and DNA G+C content) clearly indicated that the isolate represents a novel species within the genus Gymnodinialimonas. The predominant fatty acids were C19 : 0 cyclo ω8c and feature 8 (comprising C18 : 1 ω6c and/or C18 : 1 ω7c). The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. The main respiratory quinone was Q-10. Based on its phenotypic, phylogenetic, genomic and chemotaxonomic features, strain N5T represents a novel species of the genus Gymnodinialimonas, for which the name Gymnodinialimonas phycosphaerae sp. nov. is proposed. The type strain is N5T (=KCTC 82362T=NBRC 114899T).

Carbohydrate antigen 19-9 plus carcinoembryonic antigen for prognosis in colorectal cancer: An observational study.

AIM: Carcinoembryonic antigen (CEA) is a primary prognostic marker and can detect colorectal cancer (CRC) recurrence; however, it has low sensitivity. Carbohydrate antigen 19-9 (CA 19-9) can be used as a supplemental tumour marker along with CEA. The purpose of this study was to determine whether preoperative CA 19-9 added to CEA helped predict long-term prognosis and whether follow-up CA 19-9 added to CEA had additional benefits in diagnosing the recurrence of CRC. METHOD: We retrospectively assessed patients who underwent surgery for primary CRC between January 2004 and December 2015 at Seoul National University Hospital. Data on demographics, preoperative and follow-up CEA and CA 19-9 levels, recurrence and survival were obtained and analysed with respect to tumour marker levels to ascertain their prognostic and diagnostic values. RESULTS: A total of 4972 and 1530 patients were included to analyse preoperative and follow-up tumour marker levels, respectively. The 5-year relapse-free survival rates were 72.2% ± 0.8%, 52.5% ± 2.2%, 55.5% ± 3.2% and 32.1% ± 2.3% in the normal CEA and CA 19-9, high CEA, high CA 19-9, and high CEA and high CA 19-9 groups, respectively (all P < 0.001). Patients whose elevated CEA or CA 19-9 levels reduced to normal levels had better survival outcomes than those with postoperatively elevated levels. Elevated follow-up CA 19-9 and CEA levels were related to higher incidences of distant metastasis (CA 19-9, 14.0% vs. 23.1%, P = 0.004; CEA, 12.6% vs. 30.1%, P < 0.001) but not to local recurrence. Combined follow-up CEA and CA 19-9 increased the sensitivity for recurrence to 31.4%, with a 5% difference from the sensitivity of CEA alone. In the subgroup with high preoperative CA 19-9 levels, sensitivity increased by 18.2% overall. CONCLUSION: CA 19-9 is a valuable prognostic and diagnostic marker for CRC when used adjunctively with CEA and can be a supplementary marker with CEA to improve sensitivity, especially with elevated preoperative CA 19-9.