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BackgroundGastric intestinal metaplasia (GIM), particularly the incomplete subtype (Inc IM), is strongly associated with increased gastric cancer (GC) risk. However, its role as a true precursor lesion remains uncertain.ObjectiveWe aimed to delineate the molecular identity, differentiation potential and oncogenic relevance of Inc IM.MethodsSpatial transcriptomics using a custom lineage-enriched panel was applied to profile GIM and GC tissues. Subtype-specific GIM organoid models were developed for DNA methylation and chromatin accessibility profiling. Single-cell RNA sequencing was performed to evaluate differentiation capacity.ResultsSpatial transcriptomics revealed that Inc IM potentially originates from the deep antral gland cells and harbours a hybrid transcriptomic signature incorporating gastric, small intestinal and large intestinal lineages across both differentiated and stem/progenitor compartments. DNA methylation profiling of subtype-specific organoids showed that Inc IM exhibits extensive intergenic hypermethylation, resembling native antral mucosa. In contrast, complete subtype was marked by promoter hypermethylation of tumour suppressor genes and displayed a more fully intestinalised epigenetic profile. Organoid models recapitulated subtype-specific traits and demonstrated lineage plasticity. Spatial mapping of GC samples revealed an enrichment of Inc IM-like cells, particularly within microsatellite stable tumours. Approximately 76% of the GCs analysed were linked to GIM, while the remaining (24%) appeared to be associated with deep antral differentiation.ConclusionsInc IM represents a phenotypically unstable and epigenetically deregulated metaplastic state with dual-lineage potential and molecular resemblance to GC. These findings establish Inc IM as a true precursor to GC and underscore the importance of active surveillance and early intervention strategies.

This paper introduces a nonlinear autopilot capable of controlling the steady-state lateral thrust input for dual-controlled missiles based on the guidance purpose. The proposed controller leverages the multi-input single-output structure per axis characteristic of dual-controlled missiles. It uses the lateral thrust input as an additional tool to actively select a control strategy according to flight conditions. To meet this design objective, we employ a control structure that allocates attitude control as an additional command, along with maneuvering acceleration, in a process known as command allocation. As the allocated attitude control is executed, the lateral thrust input converges to a predetermined value. This allows the proposed method to adjust the lateral thrust input based on various control strategies. Furthermore, the proposed autopilot is designed to avoid the direct use of true values of parameters and variables that are challenging to measure accurately, such as aerodynamic coefficients and angle-of-attack. The practical advantage of the proposed controller is further enhanced by the application of the sliding mode control technique, renowned for its robustness against unknown disturbances. To verify the effectiveness of the proposed algorithm, we conduct a numerical simulation under various operating conditions. The results show that the proposed autopilot successfully executes various necessary control strategies by suitably adjusting the lateral thrust input while tracking the maneuvering acceleration command.

Combining standard surgical procedures with personalized chemotherapy and the continuous monitoring of cancer progression is necessary for effective NSCLC treatment. In this study, we developed liposomal nanoparticles as theranostic agents capable of simultaneous therapy for and imaging of target cancer cells. Copper-64 (64Cu), with a clinically practical half-life (t1/2 = 12.7 h) and decay properties, was selected as the radioisotope for molecular PET imaging. An anti-epidermal growth factor receptor (anti-EGFR) antibody was used to achieve target-specific delivery. Simultaneously, the chemotherapeutic agent doxorubicin (Dox) was encapsulated within the liposomes using a pH-gradient method. The conjugates of 64Cu-labeled and anti-EGFR antibody-conjugated micelles were inserted into the doxorubicin-encapsulating liposomes via a post-insertion procedure (64Cu-Dox-immunoliposomes). We evaluated the size and zeta-potential of the liposomes and analyzed target-specific cell binding and cytotoxicity in EGFR-positive cell lines. Then, we analyzed the specific therapeutic effect and PET imaging of the 64Cu-Dox-immunoliposomes with the A549 xenograft mouse model. In vivo therapeutic experiments on the mouse models demonstrated that the doxorubicin-containing 64Cu-immunoliposomes effectively inhibited tumor growth. Moreover, the 64Cu-immunoliposomes provided superior in vivo PET images of the tumors compared to the untargeted liposomes. We suggest that nanoparticles will be the potential platform for cancer treatment as a widely applicable theranostic system.

Background: Gastric cancer is one of the most prevalent malignancies worldwide and the fourth leading cause of cancer-related mortality. Protein ubiquitination and deubiquitination regulate protein stability as post-translational modifications, playing essential roles in tumorigenesis. Although UCHL1, a deubiquitinating enzyme (DUB), is implicated in the progression of several cancer types, its role in gastric cancer remains unclear. Methods: Kaplan–Meier analysis and gastric cancer patient tissues were used to assess UCHL1 expression. Cell viability assay, colony-forming assay, and transwell migration and invasion assay were performed to evaluate cell growth. Immunoprecipitation and Western blotting analyzed protein expression and interactions. Results: This study demonstrates that UCHL1 expression is markedly upregulated in gastric cancer tissues compared to normal tissues. Elevated UCHL1 expression is associated with poor patient prognosis, supporting its potential role as an oncogenic factor. Reduced UCHL1 expression suppressed cell proliferation, migration, and invasion in gastric cancer cell lines. As the underlying mechanism, we identified CIP2A, a known oncogenic regulator of c-Myc, as a downstream effector of UCHL1. UCHL1 knockdown reduced CIP2A protein levels via deubiquitination, attenuated c-Myc signaling, and decreased expression of key cell cycle regulators. Furthermore, UCHL1 knockdown significantly downregulated cyclin D1 expression, arresting the cell cycle in the G1 phase and inhibiting cell proliferation. Conclusions: Collectively, our findings reveal that UCHL1 promotes gastric cancer progression, highlighting it as a potential therapeutic target.

Individual differences in colour perception, as evidenced by the popular debate of “The Dress” picture, have garnered additional interest with the popularisation of additional, similar photographs. We investigated which colorimetric characteristics were responsible for individual differences in colour perception. All objects of the controversial photographs are composed of two representative colours, which are low in saturation and are either complementary to each other or reminiscent of complementary colours. Due to these colorimetric characteristics, we suggest that one of the two complementary pixel clusters should be estimated as the illuminant hue depending on assumed brightness. Thus, people perceive the object's colours as being biased toward complementarily different colour directions and perceive different pixel clusters as chromatic and achromatic. Even though the distance between colours that people perceive differently is small in colour space, people perceive the object's colour as differently categorized colours in these ambiguous photographs, thereby causing debate. We suggest that people perceive the object's colours using different “modes of colour appearance” between surface-colour and self-luminous modes.

Recently, the commercialization of hybrid machine tools that combine directed energy deposition (DED) additive manufacturing (AM) technology and subtractive manufacturing (SM) has rapidly progressed. This technology trend has been developed to meet the market demand for processing quality (precision) and productivity, and to produce products such as lightweight parts, and complex and special functional parts, as well as to facilitate mold production and part repair. Compared to SM technology, metal AM technology has limitations in terms of surface quality and shape accuracy. Therefore, post-processing is necessary for the AM output. Laser-assisted machining (LAM) is an innovative hybrid technique in which surface quality and productivity can be improved by enhancing the machinability of difficult-to-cut materials. LAM studies have mainly been performed on titanium alloys, nickel based alloys and ceramic materials. However, except for ceramics, no high-strength material studies have been conducted to analyze the LAM process machining characteristics of workpieces fabricated by AM process. Therefore, in this study, LAM is applied to post-processing of output fabricated by AM of Ti-6Al-4V. DED device was developed using metal powder feeder and a laser. The Ti-6Al-4V workpieces were successfully fabricated through many tests. The cutting depth for LAM was selected through thermal analysis for LAM of the fabricated workpiece. Compared to the case of traditional machining without preheating, machining characteristics in LAM experiments were analyzed and property testing was performed.

The high-entropy alloy (HEA) has recently attracted significant interest due to its novel alloy design concept and exceptional mechanical properties, which may exhibit either a single or multi-phase structure. Specifically, refractory high-entropy alloys (RHEA) composed of titanium, niobium, and nickel-based HEA demonstrate remarkable mechanical properties at elevated temperatures. Additive manufacturing (AM), specifically Direct Energy Deposition (DED), is efficient in fabricating high-entropy alloys (HEA) owing to its fast-cooling rates, which promote uniform microstructures and reduce defects. This study involved the fabrication of the Ti33Nb28Cr11V11Ni17 (Ti-Nb-Cr-V-Ni) RHEA utilizing DED. Additionally, the post-processing of the fabricated alloy is conducted using conventional machining (CM) and laser-assisted machining (LAM). The results indicate thermal conductivity and specific heat increased, whereas tensile strength reduced with rising temperature. Significant softening was observed above 800 °C, resulting in a considerable decrease in tensile strength. Furthermore, the LAM caused material softening and reduced the cutting force by 60.0% relative to CM. Furthermore, the chemical composition of Ti-Nb-Cr-V-Ni remained unaffected even after post-processing with CM and LAM. The research indicates that post-processing with LAM is essential for developing resilient RHEA for practical use.

Highly entropy alloys (HEAs) are novel materials that have great potential for application in aerospace and marine engineering due to their superior mechanical properties and benefits over conventional materials. NiCrCoFe, also referred to as Ni-based HEA, has exceptional low-temperature strength and microstructural stability. However, HEAs have limited corrosion resistance in some environments, such as a 3.5 wt% sodium chloride (NaCl) solution. Adding corrosion-resistant elements such as molybdenum (Mo) to HEAs is expected to increase their corrosion resistance in a variety of corrosive environments. Metal additive manufacturing reduces production times compared to casting and eliminates shrinkage issues, making it ideal for producing homogeneous HEA. This study used directed energy deposition (DED) to create Cr25-xCo25Ni25Fe25Mox (x = 0, 5, 10%) HEAs. Tensile strength and potentiodynamic polarization tests were used to assess the materials’ mechanical properties and corrosion resistance. The mechanical tests revealed that adding 5% Mo increased yield strength (YS) by 20.1% and ultimate tensile strength (UTS) by 9.5% when compared to 0% Mo. Adding 10% Mo led to a 32.5% increase in YS and a 20.4% increase in UTS. Potentiodynamic polarization tests were used to assess corrosion resistance in a 3.5-weight percent NaCl solution. The results showed that adding Mo significantly increased initial corrosion resistance. The alloy with 5% Mo had a higher corrosion potential (Ecorr) and a lower current density (Icorr) than the alloy with 0% Mo, indicating improved initial corrosion resistance. The alloy containing 10% Mo had the highest corrosion potential and the lowest current density, indicating the slowest corrosion rate and the best initial corrosion resistance. Finally, Cr25-xCo25Ni25Fe25Mox (x = 0, 5, 10%) HEAs produced by DED exhibited excellent mechanical properties and corrosion resistance, which can be attributed to the presence of Mo.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that promotes cancer cell proliferation, invasion, and drug resistance. In this study, CIP2A expression was found to be higher in lung cancer tissues compared to adjacent normal tissues. Knocking down CIP2A in lung cancer cells reduced cell proliferation and migration. Ring finger protein 1 (RING1), a member of the RING family in the ubiquitin–proteasome system, was identified as a potential E3 ligase for CIP2A. The interaction between RING1 and CIP2A was confirmed, with RING1 regulating CIP2A ubiquitination. Knockdown of RING1 increased lung cancer cell proliferation and migration in vitro and in vivo, linked to the upregulation of CIP2A and its downstream molecules, c‐MYC and Cyclin B1. Smoking's impact on RING1 expression was examined using cigarette smoke extract (CSE), which decreased RING1 mRNA and protein levels. This led to CIP2A and c‐MYC upregulation. The carcinogen 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), a constituent of CSE, downregulated RING1 expression through DNA methyltransferase 1 (DNMT1) activation, whereas inhibition of DNMT1 restored RING1 levels. These findings highlight the DNMT1–RING1–CIP2A axis in lung cancer progression due to smoking and suggest potential therapeutic and diagnostic targets. Schematic illustration of the roles of CIP2A and RING1 in lung tumorigenesis Accumulation of DNMT1 due to NNK exposure leads to a reduction in RING1 mRNA levels. Decreased RING1 results in an accumulation of CIP2A protein levels and upregulated CIP2A suppresses PP2A activity, consequently increasing the stability of c‐MYC. Image was created with BioRender

Background: Uterine adenomyosis is defined as the presence of ectopic endometrial tissue in the myometrium of the uterus and is a known cause of chronic pelvic pain, heavy menstrual bleeding, and subfertility. However, its pathogenesis is not completely established. Several reports have suggested that vascular endothelial cell growth factor (VEGF) may be associated with the progression of adenomyosis. The goal of this study was to evaluate the role of VEGF on pathophysiology of uterine adenomyosis by comparing expression of VEGF in the same uterus and in the endometrium and myometrium, with patients’ adenomyosis. Methods: We analyzed 22 premenopausal patients with a focal type of uterine adenomyosis who received an adenomyomectomy between December 2019 and April 2020 at our hospital. All patients were preoperatively treated with gonadotropin-releasing hormone(GnRH) analogs. During these surgeries, samples were obtained from the uterus of each patient which included the adenomyosis lesion, the myometrium without adenomyosis, and endometrial tissue. Immunohistochemistry stain of VEGF and real-time polymerase chain reaction (RT-PCR) of VEGF expression were compared for each of three points in the uterus. We also compared microvascular density in the adenomyosis lesion between the ectopic endometrial gland and myometrial stroma. Results: VEGF expression was found to be increased in adenomyotic lesions and myometrium compared with the eutopic endometrium (p < 0.0001). In addition, RT-PCR indicated higher VEGF expression in the myometrial and adenomyosis tissues than in the eutopic endometrium (p < 0.05). In each patient, a comparison of microvascular density (MVD) measurements of the eutopic endometrium with an endometrial component and stroma in the adenomyosis tissue indicated a significant increase in the stroma comprising the myometrium (p = 0.02). Conclusions: VEGF contributes to the progression of uterine adenomyosis and may be more strongly activated in the stromal component of the myometrium than in the endometrial (eutopic or ectopic) component of the adenomyosis in the same uterus. This suggests that VEGF plays a significant role in the muscular component of the endometrium during the progression of adenomyosis.