Cd2+-Specific Fluorescence Response of Methoxy-Substituted N,N-Bis(2-quinolylmethyl)-2-methoxyaniline Derivatives.

The N3O1 tetradentate ligand, TriMeOBQMOA (N,N-bis(5,6,7-trimethoxy-2-quinolylmethyl)-2-methoxyaniline), was developed as a Cd2+-specific fluorescent sensor. The structure of TriMeOBQMOA is half of TriMeOBAPTQ (N,N,N',N'-tetrakis(5,6,7-trimethoxy-2-quinolylmethyl)-1,2-bis(2-aminophenoxy)ethane), which is a tetrakisquinoline derivative of the well-known calcium chelator BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). The fluorescent Cd2+ selectivity of TriMeOBAPTQ (IZn/ICd = 5.3% in the presence of 3 equiv of metal ions in MeOH-HEPES buffer (9:1)) comes from the formation of fluorescent dinuclear cadmium (M2L) and nonfluorescent OH-bridged dizinc ((µ-OH)M2L) complexes. TriMeOBQMOA also exhibits excellent Cd2+ specificity in fluorescence enhancement (IZn/ICd = 2.3% in the presence of 5 equiv of metal ions in DMF-HEPES buffer (1:1, HEPES 50 mM, KCl 0.1 M, pH = 7.5)) via substantial formation of a highly fluorescent bis(µ-chloro)dinuclear cadmium complex ([Cd2(µ-Cl)2L2]2+), which is in equilibrium with the mononuclear Cd2+ complex ([CdLCl]+), and extremely poor stability of the TriMeOBQMOA-Zn2+ complex. The all-nitrogen derivatives of BQMOA and BAPTQ, namely, N,N-BQDMPHEN (N,N-bis(2-quinolylmethyl)-N',N'-dimethyl-1,2-phenylenediamine) and BPDTQ (N,N,N',N'-tetrakis(2-quinolylmethyl)-2,2'-(N,N'-dimethylethylenediamino)dianiline), respectively, and their methoxy-substituted derivatives were also prepared, and the fluorescent metal ion sensing properties are discussed.

Evaluation of oxygen-containing pentadentate ligands with pyridine/quinoline/isoquinoline binding sites via the structural and electrochemical properties of mononuclear copper(II) complexes.

Eighteen mononuclear copper(II) complexes with oxygen-containing N4O1 pentadentate ligands were prepared. The ligand library consists of 2-aminoethanol derivatives ((Ar1CH2)(Ar2CH2)NCH2CH2OCH2Ar3) bearing three nitrogen-containing heteroaromatics (Ars) including pyridine, quinoline and isoquinoline via a methylene linker. Systematic replacements of pyridine binding sites with quinolines and isoquinolines reveal the general trends in the perturbation of bond distances and angles, the redox potential and the absorption maximum wavelength of the copper(II) complexes, depending on the position and number of (iso)quinoline heteroaromatics. The small effect on the redox potentials resulting from quinoline substitution at the Ar3 position (near oxygen) of the ligand comes from the steric hindrance of the peri hydrogen atom in the quinoline moiety at this position, which removes the counter anion to enhance the coordination of quinoline nitrogen and ether oxygen atoms to the metal centre. In the absorption spectra of copper(II) complexes in the d-d transition region, the quinoline substitution at this site (Ar3) exhibits an opposite effect to those at the Ar1 and Ar2 sites. The electronic and steric contributions of the heteroaromatic binding sites to the ligand properties are comprehensively discussed.

Conformation state-specific monobodies regulate the functions of flexible proteins through conformation trapping.

Synthetic binding proteins have emerged as modulators of protein functions through protein-protein interactions (PPIs). Because PPIs are influenced by the structural dynamics of targeted proteins, investigating whether the synthetic-binders-based strategy is applicable for proteins with large conformational changes is important. This study demonstrates the applicability of monobodies (fibronectin type-III domain-based synthetic binding proteins) in regulating the functions of proteins that undergo tens-of-angstroms-scale conformational changes, using an example of the A55C/C77S/V169C triple mutant (Adktm ; a phosphoryl transfer-catalyzing enzyme with a conformational change between OPEN/CLOSED forms). Phage display successfully developed monobodies that recognize the OPEN form (substrate-unbound form), but not the CLOSED form of Adktm . Two OPEN form-specific clones (OP-2 and OP-4) inhibited Adktm kinase activity. Epitope mapping with a yeast-surface display/flow cytometry indicated that OP-2 binds to the substrate-entry side of Adktm , whereas OP-4 binding occurs at another site. Small angle X-ray scattering  coupled with size-exclusion chromatography (SEC-SAXS) indicated that OP-4 binds to the hinge side opposite to the substrate-binding site of Adktm , retaining the whole OPEN-form structure of Adktm . Titration of the OP-4-Adktm complex with Ap5 A, a transition-state analog of Adktm , showed that the conformational shift to the CLOSED form was suppressed although Adktm retained the OPEN-form (i.e., substrate-binding ready form). These results show that OP-4 captures and stabilizes the OPEN-form state, thereby affecting the hinge motion. These experimental results indicate that monobody-based modulators can regulate the functions of proteins that show tens-of-angstroms-scale conformational changes, by trapping specific conformational states generated during large conformational change process that is essential for function exertion.

Treatment persistence of interleukin-17 inhibitor class drugs among patients with psoriasis in Japan: a retrospective database study.

BACKGROUND AND OBJECTIVE: Real-world evidence on persistence of interleukin-17 inhibitors (IL-17i) as a drug class among Japanese patients with psoriasis is lacking. Hence, we aimed to describe persistence rates of IL-17is among patients with psoriasis including psoriasis vulgaris (PsO), psoriatic arthritis (PsA), and generalized pustular psoriasis (GPP) or erythrodermic psoriasis (EP) in Japan. METHODS: We analyzed claims data from the Medical Data Vision database. Patients ≥15 years old with a psoriasis diagnosis and an IL-17i prescription between November 2016 and August 2020 were included and followed through August 2021. Persistence rates of the IL-17i class among patients with psoriasis and its subtypes (PsO, PsA, and GPP or EP), and persistence rates of ixekizumab, secukinumab, or brodalumab among patients with PsO or PsA were analyzed using Kaplan-Meier method. Analyses were conducted in the bio-naïve and bio-experienced subgroups. RESULTS: The IL-17i class had >50% persistence rates up to 36 months among patients with psoriasis and its subtypes (PsO, PsA, and GPP or EP). 36-Month persistence rates for ixekizumab, secukinumab, and brodalumab were 46.2% to 57.7% in patients with PsO and 43.0% to 48.4% in patients with PsA. Across analyses, bio-naïve patients demonstrated similar or greater persistence rates than bio-experienced patients. CONCLUSION: IL-17is' persistence rates over 36 months were >50% among patients with psoriasis and its subtypes (PsO, PsA, and GPP or EP) in Japan.

Reactivity regulation for olefin metathesis-catalyzing ruthenium complexes with sulfur atoms at the terminal of 2-alkoxybenzylidene ligands.

For regulating the olefin metathesis (OM) activity of the Hoveyda-Grubbs second-generation complex (HG-II), the structural modification of the benzylidene ligand is a useful strategy. This paper reports the effect of a chalcogen atom placed at the end of the benzylidene group on the catalytic properties of HG-II derivatives, using complexes with a thioether or ether component in the benzylidene ligand (ortho-Me-E-(CH2)2O-styrene; E = S, O). Nuclear magnetic resonance and X-ray crystallographic analyses of the complex with a thioether moiety (E = S) proved the (O,S)-bidentate and trans-dichlorido coordination for the complex. A stoichiometric ligand exchange between HG-II and the benzylidene ligand (E = S) produced the corresponding complex with an 86% yield, confirming higher stability of the complex (E = S) than that of HG-II. Despite the bidentate chelation, the complex (E = S) exhibited OM catalytic activity, indicating the exchangeability of the S-chelating ligand with an olefinic substrate. The green solution color, a characteristic of HG-II derivatives, was retained after the complex (E = S)-mediated OM reactions, indicating high catalyst durability. Conversely, the complex (E = O) rapidly initiated OM reactions; however, it showed low catalyst durability. In the OM reactions conducted in the presence of methanol, the complex (E = S) exhibited higher yields than the complex (E = O) and HG-II: the S-coordination increased the catalyst tolerance to methanol. A coordinative atom (such as sulfur) placed at the terminal of the benzylidene ligand can precisely regulate the reactivity of HG-II derivatives.

Effect of methoxy substituents on fluorescent Zn2+/Cd2+ selectivity of bisquinoline derivatives with a N,N'-dimethylalkanediamine skeleton.

BQDMEN (N,N'-bis(2-quinolylmethyl)-N,N'-dimethylethylenediamine) and its 6-methoxyquinoline derivative (6-MeOBQDMEN) are fluorescent Zn2+ sensors with minor response to Cd2+ (IZn/ICd = 3.9 for BQDMEN and IZn/ICd = 2.2 for 6-MeOBQDMEN in the presence of 1 equiv. of metal ion). Nevertheless, the introduction of three methoxy substituents at the 5,6,7-position of both quinoline rings of BQDMEN reversed the fluorescent metal ion selectivity to favor Cd2+ (IZn/ICd = 0.22 for TriMeOBQDMEN in the presence of 1 equiv. of metal ion). This reversal of Zn2+/Cd2+ preference in fluorescence enhancement by trimethoxy substitution was also valid for 1,3-propanediamine derivatives. The X-ray crystallography, ESI-MS, fluorescence lifetime and pH profile of the fluorescence intensity suggest that the dinuclear cadmium complex is a key component of the fluorescent Cd2+ selectivity in TriMeOBQDMEN.

A Modified Sliding-Lengthening Approach to Tendon Lengthening with a Locking Mechanism Suture: A Technical Note.

There are various techniques used for tendon lengthening, of which Z-lengthening and sliding-lengthening are the most frequently performed. In patients with cerebral palsy, tendon lengthening may often be necessary at multiple sites. However, they can cause various complications, such as inaccurate extension, overextension, and a lack of tendon continuity. We modified the sliding-lengthening technique with a locking mechanism to address these issues. This technical note aims to describe the surgical technique and pitfalls associated with the modified sliding-lengthening approach and suture locking mechanism. The tendon was exposed and stabilized using sterilized spitz tubes and was then threaded so that each loop length was equivalent to the amount of tendon extension. Symmetrical hemisection of both ends of the tendon was performed, and the tendon was carefully extended to create a tense loop. The modified sliding-lengthening technique with the locking suture mechanism may be an advantageous method that accurately addresses extension volume, prevents hyperextension, and maintains tendon continuity, even when smaller incisions are used.

Cell-based analysis reveals that sex-determining gene signals in Ostrinia are pivotally changed by male-killing Wolbachia.

Wolbachia, a maternally transmitted bacterium, shows male-killing, an adaptive phenotype for cytoplasmic elements, in various arthropod species during the early developmental stages. In lepidopteran insects, lethality of males is accounted for by improper dosage compensation in sex-linked genes owing to Wolbachia-induced feminization. Herein, we established Ostrinia scapulalis cell lines that retained sex specificity per the splicing pattern of the sex-determining gene doublesex (Osdsx). We found that Wolbachia transinfection in male cell lines enhanced the female-specific splice variant of Osdsx (OsdsxF ) while suppressing the male-specific variant (OsdsxM ), indicating that Wolbachia affects sex-determining gene signals even in vitro. Comparative transcriptome analysis isolated only two genes that behave differently upon Wolbachia infection. The two genes were respectively homologous to Masculinizer (BmMasc) and zinc finger-2 (Bmznf-2), male-specifically expressed sex-determining genes of the silkworm Bombyx mori that encode CCCH-type zinc finger motif proteins. By using cultured cells and organismal samples, OsMasc and Osznf-2 were found to be sex-determining genes of O. scapulalis that are subjected to sex-specific alternative splicing depending upon the chromosomal sex, developmental stage, and infection status. Overall, our findings expound the cellular autonomy in insect sex determination and the mechanism through which sex is manipulated by intracellular selfish microbes.

Reproductive advantage of the winners of male-male competition in Drosophila prolongata.

In the resource-defence mating system, where males compete for limited resources to acquire females, male traits associated with fighting ability are selected, leading to the evolution of sexual dimorphism. However, the evolution of sexual dimorphism is also driven by other mechanisms, such as female selection. Therefore, to elucidate the evolutionary mechanisms of male traits, it is necessary to clarify their contribution to fitness through male-male competition. In this regard, it is surprising that numerous studies on sexually dimorphic species have assumed the resource-defence mating system without directly examining the relationship between resource-defending behaviour and mating success. In a sexually dimorphic fruit fly, Drosophila prolongata, the presence of the resource-defence mating system has been suggested, but technical difficulties had prevented spatial quantification of the resource-defending behaviour. In this study, by using an automated behaviour analysis tool previously developed, we located the occurrence of male-male competition and courtship to investigate their relationship in D. prolongata, considering the position of food resources. We found that the male-male competition led to the exclusive occupation of resources, increasing the courtship opportunities of the resource holders. These results illustrate the importance of resource-defending for reproductive success in D. prolongata.

Association between eating behavior and the immediate neural activity caused by viewing food images presented in and out of awareness: A magnetoencephalography study.

Obesity is a serious health problem in modern society. Considering the fact that the outcomes of treatments targeting appetitive behavior are suboptimal, one potential reason proposed for these poor outcomes is that appetitive behavior is driven more by unconscious decision-making processes than by the conscious ones targeted by traditional behavioral treatments. In this study, we aimed to investigate both the conscious and unconscious decision-making processes related to eating behavior, and to examine whether an interaction related to eating behavior exists between conscious and unconscious neural processes. The study was conducted on healthy male volunteers who viewed pictures of food and non-food items presented both above and below the awareness threshold. The oscillatory brain activity affected by viewing the pictures was assessed by magnetoencephalography. A visual backward masking procedure was used to present the pictures out of awareness. Neural activity corresponding to the interactions between sessions (i.e., food or non-food) and conditions (i.e., visible or invisible) was observed in left Brodmann's areas 45 and 47 in the high-gamma (60-200 Hz) frequency range. The interactions were associated with eating behavior indices such as emotional eating and cognitive restraint, suggesting that conscious and unconscious neural processes are differently involved in eating behavior. These findings provide valuable clues for devising methods to assess conscious and unconscious appetite regulation in individuals with normal or abnormal eating behavior.

An Indirect Cost of Male-Male Aggression Arising from Female Response.

Animal behavior is often polymorphic between individuals within a population. A cost/benefit balance of a particular behavioral pattern may be influenced by social interaction with other individuals with different behavioral patterns. Males of a fruitfly, Drosophila prolongata, show genetically defined polymorphism in aggressiveness and boldness against rival males. Males of the H strain are highly aggressive, and their fights tend to escalate into boxing, the highest level of aggressive interaction. H males are also bold against sneaker males and do not hesitate to perform leg vibration (LV), a courtship behavior that is vulnerable to interception of the female by surrounding rival males. In contrast, males of the L strain rarely engage in boxing and do not perform LV in the presence of rival males. We examined their mating success in small experimental populations. The mating success of L males was higher in a pure L population than in a mixed population with H males, whereas that of H males was higher in a mixed population than in a pure H population. Notably, this 'cost of aggression' in a pure H population seemed not directly derived from the male-to-male interaction but was imposed by the female's response of escaping from fighting males, compromising the benefit of the resource monopolization as territory.

Cd2+-selective fluorescence response of TQEN (N,N,N',N'-tetrakis(2-quinolylmethyl)ethylenediamine) derivatives bearing ether oxygen-binding sites.

Moderate Zn2+ selectivity over Cd2+ (IZn/ICd = 1.6) in the fluorescence enhancement of TQEN (N,N,N',N'-tetrakis(2-quinolylmethyl)ethylenediamine) was changed to Cd2+ preference via the introduction of a methoxymethyloxy (MOMO) substituent at the 8-position of one of the four quinoline rings (IZn/ICd = 0.2). Thus, 8-MOMOTQEN (N-(8-methoxymethyloxy-2-quinolylmethyl)-N,N',N'-tris(2-quinolylmethyl)ethylenediamine) showed not only high Cd2+-selectivity but also an enhanced fluorescence quantum yield upon Cd2+ binding and high sensitivity for Cd2+ detection as shown by ϕCd = 0.065 and LOD (limit of detection) = 19 nM. The two oxygen atoms of the MOMO group in 8-MOMOTQEN play a crucial role in the fluorescent metal-ion selectivity because the corresponding hydroxy (8-OHTQEN) and methoxy (8-MeOTQEN) derivatives resulted in a poor fluorescent response and metal selectivity, respectively. Another N6O2 ligand, N,N'-bis(8-methoxy-2-quinolylethyl)-N,N'-bis(2-quinolylmethyl)ethylenediamine ((8-MeO)2TQEN) exhibited a Zn2+-selective fluorescence enhancement (IZn/ICd = 2.2), indicating the superiority of the MOMO group for the selective sensing of Cd2+.

Drosophila suzukii preferentially lays eggs on spherical surfaces with a smaller radius.

Drosophila suzukii is an agricultural pest that predominantly harms small fruits, having a serrated ovipositor that is able to pierce the skin of ripening fruits. Its oviposition preference has been studied from various aspects including chemical and physical properties of oviposition substrates. However, its preference for certain shapes or sizes of substrates has not been explored. In this study, we tested the oviposition preference of D. suzukii for artificial oviposition substrates with different surface curvatures using 27 strains recently established from wild populations collected in Japan. We found that D. suzukii laid more eggs on a surface with smaller radii (4.8 and 5.7 mm) compared with larger radii (7.7 and 9.6 mm). We also found that the most preferred radius differed among strains. Notably, the preference was independent of the volume of substrates, suggesting that D. suzukii uses the surface curvature as a cue for its oviposition site selection. These results provide an additional explanation for why D. suzukii preferentially uses small fruits as its oviposition sites.

Neural effects of viewing children's faces on mental fatigue: a magnetoencephalography study.

We examined whether the recovery from fatigue could be facilitated by viewing the children's faces. Seventeen healthy mothers with child or children over 6 years old participated in our experiment. After performing a 2-back task for 40 min, they viewed the pictures of children's and adult's faces in the target and control conditions, respectively. The target and control conditions were performed on the separate days in a two-crossover design. Neural activity caused by viewing the children's faces was recorded using magnetoencephalography and electrocardiography was performed to assess the index of heart rate variability (low-frequency component power/high-frequency component power ratio, LF/HF) reflecting fatigue. The subjective level of mental fatigue sensation and LF/HF ratio was decreased after viewing the children's faces and the overactivation of the visual cortex caused by performing the 2-back task, assessed by the alteration of alpha band power in the visual cortex, was attenuated by viewing the children's faces, suggesting that viewing the children's faces affected the time course of mental fatigue after performing the 2-back task.

A case of BNT162b2 COVID-19 vaccine-associated fulminant myocarditis in a very elderly woman.

Coronavirus disease 2019 (COVID-19) vaccination is reportedly safe and effective. The histologic features of post-COVID-19 vaccination myocarditis are unknown. We present a case of a 77-year-old Japanese woman diagnosed with eosinophilic myocarditis using endomyocardial biopsy, 7 days after the second dose of BNT162b2 COVID-19 vaccine. Steroid pulse therapy was effective.

Factors related to self-care behaviors among hospitalized patients with heart failure in Japan, based on the European Heart Failure Self-Care Behaviour Scale.

[Purpose] The characteristics of heart failure in hospitalized patients with poor self-care behaviors are unknown. We investigated factors associated with self-care behaviors by using the European Heart Failure Self-Care Behaviour Scale (EHFScBS) in heart failure patients based on three comprehensive concepts. [Participants and Methods] This was a cross-sectional single-center study of heart failure patients hospitalized at a tertiary-care hospital. We investigated age, gender, family living together/apart, employment, and the Specific Activity Scale (SAS). A physical therapist provided the EHFScBS one time to determine the patients' pre-hospital self-care behavior status. The 12 items of the EHFScBS were classified into the following three categories: Maintenance, Monitoring, and Management. [Results] The median age of the 39 consecutive patients was 81 years. A multiple regression analysis revealed that the factors exhibiting significant associations were the SAS score (ß=0.504) for Management and age (ß=-0.403) for the total EHFScBS score (adjusted by the number of hospitalizations for heart failure). Maintenance and Monitoring were not significantly associated with the survey items. [Conclusion] These data indicate that self-care education for hospitalized patients with heart failure leads to individualized approaches based on characteristics such as age and physical activity capacity.

Neural mechanism by which physical fatigue sensation suppresses physical performance: a magnetoencephalography study.

The right dorsolateral prefrontal cortex (DLPFC) has been proposed to be the brain region regulating performance through fatigue sensation in fatigue, but direct evidence has been lacking for right DLPFC activation when physical performance is suppressed in the presence of fatigue sensation. We examined whether the right DLPFC is activated when physical performance is suppressed by remembering a physical fatigue sensation. Eighteen healthy male volunteers participated. They performed a rest session followed by a handgrip session to induce physical fatigue sensation. Then, they were instructed to remember the state of the right hand with (i.e., the target condition) and without (i.e., the control condition) fatigue sensation as experienced in the handgrip and rest sessions, respectively while performing motor imagery of maximum handgrip of the right hand. Neural activity during both conditions was recorded using magnetoencephalography. The level of fatigue sensation was higher in the target condition than in the control condition. Decreases of handgrip strength and beta band power in the right Brodmann's area 46 were observed in the target condition, suggesting that the right DLPFC is involved in the regulation of physical performance through fatigue sensation. These findings may help elucidate the neural mechanisms regulating performance under fatigue conditions.

Effect of Impaired T Cell Receptor Signaling on the Gut Microbiota in a Mouse Model of Systemic Autoimmunity.

OBJECTIVE: T cell receptor (TCR) signaling abnormalities and gut dysbiosis are thought to be involved in the development of systemic lupus erythematosus (SLE). However, it is not known whether these mechanisms are interrelated. This study was undertaken to explore the impact of defective TCR signaling on microbiota-driven immune responses and the consequent triggering of systemic autoimmunity. METHODS: The responses of B6SKG mice harboring a mutation in ZAP-70 leading to spontaneous development of SLE were evaluated under specific pathogen-free (SPF) and germ-free (GF) conditions. The gut microbiome was analyzed using 16S ribosomal RNA sequencing. Secretory IgA production in the gut and follicular helper T (Tfh) cell development in the spleen and Peyer's patches were analyzed. Interleukin-17 (IL-17)-deficient mice and segmented filamentous bacteria (SFB)-specific TCR-transgenic mice were used to examine the role of IL-17 and thymic selection. RESULTS: SLE development in B6SKG mice was significantly more attenuated under GF conditions than under SPF conditions. The gut microbiota in B6SKG mice was altered, which was associated with the expansion of SFB and consequent development of SLE by driving Th17 cell differentiation, which was in turn blunted by IL-17 deficiency. Notably, although systemic Tfh development and autoantibody IgG response were enhanced, local gut Tfh and IgA responses were impaired. Moreover, experiments in SFB-specific TCR-transgenic mice revealed that this differential response was caused by altered thymic selection of self- and microbiota-reactive TCR because of defective TCR signaling. CONCLUSION: Our findings indicate that defective TCR signaling alters the gut microbiota and promotes systemic autoimmunity by driving Th17 cell differentiation.

Enlarged folds on endoscopic gastritis as a predictor for submucosal invasion of gastric cancers.

BACKGROUND: Accurate diagnosis of the depth of gastric cancer invasion is crucial in clinical practice. The diagnosis of gastric cancer depth is often made using endoscopic characteristics of the tumor and its margins; however, evaluating invasion depth based on endoscopic background gastritis remains unclear. AIM: To investigate predicting submucosal invasion using the endoscopy-based Kyoto classification of gastritis. METHODS: Patients with gastric cancer detected on esophagogastroduodenoscopy at Toyoshima Endoscopy Clinic were enrolled. We analyzed the effects of patient and tumor characteristics, including age, sex, body mass index, surveillance endoscopy within 2 years, current Helicobacter pylori infection, the Kyoto classification, and Lauren's tumor type, on submucosal tumor invasion and curative endoscopic resection. The Kyoto classification included atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. Atrophy was characterized by non-reddish and low mucosa. Intestinal metaplasia was detected as patchy whitish or grayish-white flat elevations, forming an irregular uneven surface. An enlarged fold referred to a fold width ≥ 5 mm in the greater curvature of the corpus. Nodularity was characterized by goosebump-like multiple nodules in the antrum. Diffuse redness was characterized by uniform reddish non-atrophic mucosa in the greater curvature of the corpus. RESULTS: A total of 266 gastric cancer patients (mean age, 66.7 years; male sex, 58.6%; mean body mass index, 22.8 kg/m2) were enrolled. Ninety-three patients underwent esophagogastroduodenoscopy for surveillance within 2 years, and 140 had current Helicobacter pylori infection. The mean Kyoto score was 4.54. Fifty-eight cancers were diffuse-type, and 87 cancers had invaded the submucosa. Multivariate analysis revealed that low body mass index (odds ratio 0.88, P = 0.02), no surveillance esophagogastroduodenoscopy within 2 years (odds ratio 0.15, P < 0.001), endoscopic enlarged folds of gastritis (odds ratio 3.39, P = 0.001), and Lauren's diffuse-type (odds ratio 5.09, P < 0.001) were independently associated with submucosal invasion. Similar results were obtained with curative endoscopic resection. Among cancer patients with enlarged folds, severely enlarged folds (width ≥ 10 mm) were more related to submucosal invasion than mildly enlarged folds (width 5-9 mm, P < 0.001). CONCLUSION: Enlarged folds of gastritis were associated with submucosal invasion. Endoscopic observation of background gastritis as well as the lesion itself may help diagnose the depth of cancer invasion.