Recombinant immune complexes as vaccines against infectious diseases.

New vaccine technologies are needed to combat many existing infections and prepare better for those that may emerge in the future. The conventional technologies that rely on protein-based vaccines are still severely restricted by the sparsity and poor accessibility of available adjuvants. One possible solution to this problem is to enhance antigen immunogenicity by a more natural means by complexing it with antibodies in the form of immune complexes (ICs). However, natural ICs are impractical as vaccines, and significant research efforts have been made to generate them in recombinant form, with plant bioengineering being at the forefront of these efforts. Here, we describe the challenges and progress made to date to make recombinant IC vaccines applicable to humans.

Predictive Synthesis of Transition Metal Carbide via Thermochemical Oxocarbon Equilibrium.

Fabricating nanoscale metal carbides is a great challenge due to them having higher Gibbs free energy of formation (ΔG°) values than other metal compounds; additionally, these carbides have harsh calcination conditions, in which metal oxidation is preferred in the atmosphere. Herein, we report oxocarbon-mediated calcination for the predictive synthesis of nanoscale metal carbides. The thermochemical oxocarbon equilibrium of CO-CO2 reactions was utilized to control the selective redox reactions in multiatomic systems of Mo-C-O, contributing to the phase-forming and structuring of Mo compounds. By harnessing the thermodynamically predicted processing window, we controlled a wide range of Mo phases (MoO2, α-MoC1-x, and ß-Mo2C) and nanostructures (nanoparticle, spike, stain, and core/shell) in the Mo compounds/C nanofibers. By inducing simultaneous reactions of C-O (selective C combustion) and Mo-C (Mo carbide formation) in the nanofibers, Mo diffusion was controlled in C nanofibers, acting as a template for the nucleation and growth of Mo carbides and resulting in precise control of the phases and structures of Mo compounds. The formation mechanism of nanostructured Mo carbides was elucidated according to the CO fractions of CO-CO2 calcination. Moreover, tungsten (W) and niobium (Nb) carbides/C nanofibers have been successfully synthesized by CO-CO2 calcination. We constructed the thermodynamic map for the predictive synthesis of transition metal carbides to provide universal guideline via thermochemical oxocarbon equilibrium. We revealed that our thermochemical oxocarbon-mediated gas-solid reaction enabled the structure and phase control of nanoscale transition metal compounds to optimize the material-property relationship accordingly.

Non-suicidal self-injury motivation scale in a community sample of adolescents: a methodological study.

BACKGROUND: The prevalence of non-suicidal self-injury among South Korean adolescents has increased significantly, requiring academic attention. This methodological study aims to develop a non-suicidal self-injury motivation scale for adolescents and evaluate its validity and reliability. METHODS: In the first phase of scale development, the factors constituting self-injury motivation were identified through a literature review and analysis of online counseling data from self-injuring adolescents. In the second phase, 45 initial preliminary items were derived based on the identified factors, and 38 preliminary items were selected through content validation by experts. In the scale validation phase, the survey was conducted using 38 items. Data were collected from adolescents with a history of self-injury, using exploratory factor analysis (EFA) involving 715 participants and confirmatory factor analysis (CFA) involving 537 participants. The EFA involved 27.0% male and 73.0% female participants, with a mean age of 16.83 years, and the CFA involved 20.7% male and 79.3% female participants, with a mean age of 16.15 years. The data collected were tested for validity and reliability using SPSS 28.0 and M-plus. RESULTS: The EFA yielded four factors and 24 items. The factors were named interpersonal influence, emotion regulation, sensation seeking, and anti-suicide, and the scale had an explanatory power of 55.8%. In the CFA, the fit of the 23-item model after deleting one item with low standardized factor loadings was x2 = 1081.52 (p < .001), CFI = 0.829, RMSEA = 0.084, and SRMR = 0.075, confirming the acceptability of the self-injury motivation scale for adolescents. The scale evaluation results for convergent validity and discriminant validity met the criteria. The reliability test results showed that the overall reliability (Cronbach's α) was 0.88, and the reliability (Cronbach's α) of each factor was 0.89 for interpersonal influence, 0.83 for emotion regulation, 0.63 for sensation seeking, and 0.80 for anti-suicide, satisfying internal consistency. CONCLUSION: In this study, the self-injury motivation scale for adolescents in the community comprised four factors and 23 items. The scale can be used to examine self-injury motivation among adolescents in the community and to develop self-injury prevention intervention programs.

Kink-Controlled Gold Nanoparticles for Electrochemical Glucose Oxidation.

Enzymes in nature efficiently catalyze chiral organic molecules by elaborately tuning the geometrical arrangement of atoms in the active site. However, enantioselective oxidation of organic molecules by heterogeneous electrocatalysts is challenging because of the difficulty in controlling the asymmetric structures of the active sites on the electrodes. Here, we show that the distribution of chiral kink atoms on high-index facets can be precisely manipulated even on single gold nanoparticles; and this enabled stereoselective oxidation of hydroxyl groups on various sugar molecules. We characterized the crystallographic orientation and the density of kink atoms and investigated their specific interactions with the glucose molecule due to the geometrical structure and surface electrostatic potential.

Overview and Discussion of the Competition on Legal Information, Extraction/Entailment (COLIEE) 2023.

We summarize the 10th Competition on Legal Information Extraction and Entailment. In this tenth edition, the competition included four tasks on case law and statute law. The case law component includes an information retrieval task (Task 1), and the confirmation of an entailment relation between an existing case and a selected unseen case (Task 2). The statute law component includes an information retrieval task (Task 3), and an entailment/question-answering task based on retrieved civil code statutes (Task 4). Participation was open to any group based on any approach. Ten different teams participated in the case law competition tasks, most of them in more than one task. We received results from 8 teams for Task 1 (22 runs) and seven teams for Task 2 (18 runs). On the statute law task, there were 9 different teams participating, most in more than one task. 6 teams submitted a total of 16 runs for Task 3, and 9 teams submitted a total of 26 runs for Task 4. We describe the variety of approaches, our official evaluation, and analysis of our data and submission results.

Legal Information Retrieval and Entailment Using Transformer-based Approaches.

The challenge of information overload in the legal domain increases every day. The COLIEE competition has created four challenge tasks that are intended to encourage the development of systems and methods to alleviate some of that pressure: a case law retrieval (Task 1) and entailment (Task 2), and a statute law retrieval (Task 3) and entailment (Task 4). Here we describe our methods for Task 1 and Task 4. In Task 1, we used a sentence-transformer model to create a numeric representation for each case paragraph. We then created a histogram of the similarities between a query case and a candidate case. The histogram is used to build a binary classifier that decides whether a candidate case should be noticed or not. In Task 4, our approach relies on fine-tuning a pre-trained DeBERTa large language model (LLM) trained on SNLI and MultiNLI datasets. Our method for Task 4 was ranked third among eight participating teams in the COLIEE 2023 competition. For Task 4, We also compared the performance of the DeBERTa model with those of a knowledge distillation model and ensemble methods including Random Forest and Voting.

Health-Related Quality of Life of Post-Stroke Patients in a Public Hospital.

This study aimed to identify the correlation between influencing factors of activities of daily living (ADLs), mental health, and health-related quality of life (HRQoL) among post-stroke patients who enrolled in a transitional care service in a public hospital. This cross-sectional study involved 67 stroke patients who were enrolled in a transitional care service and visited the outpatient clinic at a public hospital in Seoul between March and December 2022. Their general characteristics, ADLs, mental health, and HRQoL were assessed. The data were analyzed using independent samples t-tests, analysis of variance, and Pearson correlation analysis, and the influencing factors were analyzed using regression analysis. HRQoL showed a statistically significant difference between patients living in different types of arrangements (t = 2.50, p = 0.015), and patients scores on the modified Rankin Scale (t = 7.08, p < 0.001). HRQoL was also significantly correlated with ADLs and mental health in stroke patients (r = -0.59, p < 0.001; r = -0.41, p < 0.001, respectively). Meanwhile, stroke severity (ß = -0.30, p = 0.002), living arrangements (ß = -0.30, p = 0.009) and ADLs (ß = -0.45, p < 0.001) were found to influence HRQoL (F = 6.87, p < 0.001, R2 = 0.47). Reduced dependence for ADLs, improvements in symptoms consequent to stroke, and support related to living arrangements contributed to improved HRQoL and interventions for post-stroke patients in the transitional care service of a public hospital.

Systematic identification of a synthetic lethal interaction in brain-metastatic lung adenocarcinoma.

Metastatic lung adenocarcinoma (LuAC) presents a significant clinical challenge due to the short latency and the lack of efficient treatment options. Therefore, identification of molecular vulnerabilities in metastatic LuAC holds great importance in the development of therapeutic drugs against this disease. In this study, we performed a genome-wide siRNA screening using poorly and highly brain-metastatic LuAC cell lines. Using this approach, we discovered that compared to poorly metastatic LuAC (LuAC-Par) cells, brain-metastatic LuAC (LuAC-BrM) cells exhibited a significantly higher vulnerability to c-FLIP (an inhibitor of caspase-8)-depletion-induced apoptosis. Furthermore, in vivo studies demonstrated that c-FLIP knockdown specifically inhibited growth of LuAC-BrM, but not the LuAC-Par, tumors, suggesting the addiction of LuAC-BrM to the function of c-FLIP for their survival. Our in vitro and in vivo analyses also demonstrated that LuAC-BrM is more sensitive to c-FLIP-depletion due to ER stress-induced activation of the c-JUN and subsequent induction of stress genes including ATF4 and DDIT3. Finally, we found that c-JUN not only sensitized LuAC-BrM to c-FLIP-depletion-induced cell death but also promoted brain metastasis in vivo, providing strong evidence for c-JUN's function as a double-edged sword in LuAC-BrM. Collectively, our findings not only reveal a novel link between c-JUN, brain metastasis, and c-FLIP addiction in LuAC-BrM but also present an opportunity for potential therapeutic intervention.

rhIL-7-hyFc and hIL-2/TCB2c combination promotes an immune-stimulatory tumor microenvironment that improves antitumor efficacy of checkpoint inhibitors.

BACKGROUND: Recombinant human interleukin (rhIL)-7-hyFc (efineptakin alfa; NT-I7) is a potent T-cell amplifier, with two IL-7 molecules fused to IgD/IgG4 elements. rhIL-7-hyFc promotes extensive infiltration of CD8+ T cells into the tumor, concurrently increasing the numbers of intratumoral PD-1+CD8+ T cells. The hIL-2/TCB2 complex (SLC-3010) inhibits tumor growth by preferential activation of CD122 (IL-2Rß)high CD8+ T cells and natural killer cells, over regulatory T cells (Tregs). We investigated the underlying mechanisms of rhIL-7-hyFc and hIL-2/TCB2c antitumor activity and the potential synergistic efficacy, specifically focusing on tumor-specific CD8+ cells within the tumor and the tumor-draining lymph nodes (tdLN). METHODS: MC38 and CT26 tumor-bearing mice were administered with 10 mg/kg rhIL-7-hyFc intramuscularly and 0.9 mg/kg hIL-2/TCB2c intravenously. Anti-PD-1 monoclonal antibody was administered intraperitoneally three times at 3-day intervals at a dose of 5 mg/kg. Tumor volume was measured to assess efficacy. To compare the composition of immune cells between each monotherapy and the combination therapy, we analyzed tumors and tdLNs by flow cytometry. RESULTS: Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME). The TME is characterized by an increased infiltration of tumor-specific CD8+ T cells, and a decreased frequency of CD39highTIM-3+ Treg cells. Most importantly, rhIL-7-hyFc increases infiltration of a CD62L+Ly108+ early progenitor population of exhausted CD8+ T cells (TPEX), which may retain long-term proliferation capacity and replenish functional effector CD8+ T cells. hIL-2/TCB2c induces differentiation of CD62L+Ly108+ TPEX rapidly into CD101+ terminally differentiated subsets (terminally exhausted T cell (TEX term)). Our study also demonstrates that rhIL-7-hyFc significantly enhances the proliferation rate of TPEX in the tdLNs, positively correlating with their abundance within the tumor. Moreover, rhIL-7-hyFc and hIL-2/TCB2c can overcome the limited therapeutic effectiveness of PD-1 blockade, culminating in the complete regression of tumors. CONCLUSIONS: rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+ T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.

Live attenuated smallpox vaccine candidate (KVAC103) efficiently induces protective immune responses in mice.

Smallpox, caused by the variola virus belonging to the genus Orthopoxvirus, is an acute contagious disease that killed 300 million people in the 20th century. Since it was declared to be eradicated and the national immunization program against it was stopped, the variola virus has become a prospective bio-weapon. It is necessary to develop a safe vaccine that protects people from terrorism using this biological weapon and that can be administered to immunocompromised people. Our previous study reported on the development of an attenuated smallpox vaccine (KVAC103). This study evaluated cellular and humoral immune responses to various doses, frequencies, and routes of administration of the KVAC103 strain, compared to CJ-50300 vaccine, and its protective ability against the wild-type vaccinia virus Western Reserve (VACV-WR) strain was evaluated. The binding and neutralizing-antibody titers increased in a concentration-dependent manner in the second inoculation, which increased the neutralizing-antibody titer compared to those after the single injection. In contrast, the T-cell immune response (interferon-gamma positive cells) increased after the second inoculation compared to that of CJ-50300 after the first inoculation. Neutralizing-antibody titers and antigen-specific IgG levels were comparable in all groups administered KVAC103 intramuscularly, subcutaneously, and intradermally. In a protective immunity test using the VACV-WR strain, all mice vaccinated with CJ-50300 or KVAC103 showed 100% survival. KVAC103 could be a potent smallpox vaccine that efficiently induces humoral and cellular immune responses to protect mice against the VACV-WR strain.

Marked enhancement of the immunogenicity of plant-expressed IgG-Fc fusion proteins by inclusion of cholera toxin non-toxic B subunit within the single polypeptide.

Immunoglobulin G (IgG)-based fusion proteins have been widely exploited as a potential vaccine delivery platform but in the absence of exogenous adjuvants, the lack of robust immunity remains an obstacle. Here, we report on a key modification that overcomes that obstacle. Thus, we constructed an IgG-Fc vaccine platform for dengue, termed D-PCF, which in addition to a dengue antigen incorporates the cholera toxin non-toxic B subunit (CTB) as a molecular adjuvant, with all three proteins expressed as a single polypeptide. Following expression in Nicotiana benthamiana plants, the D-PCF assembled as polymeric structures of similar size to human IgM, a process driven by the pentamerization of CTB. A marked improvement of functional properties in vitro and immunogenicity in vivo over a previous iteration of the Fc-fusion protein without CTB [1] was demonstrated. These include enhanced antigen presenting cell binding, internalization and activation, complement activation, epithelial cell interactions and ganglioside binding, as well as more efficient polymerization within the expression host. Following immunization of mice with D-PCF by a combination of systemic and mucosal (intranasal) routes, we observed robust systemic and mucosal immune responses, as well as systemic T cell responses, significantly higher than those induced by a related Fc-fusion protein but without CTB. The induced antibodies could bind to the domain III of the dengue virus envelope protein from all four dengue serotypes. Finally, we also demonstrated feasibility of aerosolization of D-PCF as a prerequisite for vaccine delivery by the respiratory route.

The Prognostic Significance of Vitamin D Deficiency in Korean Patients With Multiple Myeloma.

BACKGROUND: Vitamin D deficiency is relatively common among patients with multiple myeloma. The prognostic significance of vitamin D deficiency in Asian patients with multiple myeloma remains unevaluated. This study aimed to assess the prognostic value of vitamin D levels in this Korean patient population. METHODS: From September 2017 to May 2020, 98 patients were enrolled in the study. Vitamin D deficiency was defined as 25-hydroxyvitamin D level of less than 10 ng/mL. RESULTS: Thirty-six patients (36.7%) had vitamin D deficiency. These patients had significantly lower 2-year progression-free survival rates (44.8% vs. 66.9%, P = .008) and overall survival (OS) rates (2-year OS 47.2% vs. 74.2%, P = .024) compared with those without deficiency. Furthermore, patients who received vitamin D supplementation showed a trend towards improved OS compared with those who did not, with a 2-year OS rate of 51.9% vs. 33.3% (P = .14). CONCLUSION: These findings suggest that vitamin D levels are a significant prognostic factor in patients with multiple myeloma.

Novel Polytype of III-VI Metal Chalcogenides Nano Crystals Realized in Epitaxially Grown InTe.

III-VI metal chalcogenides have garnered considerable research attention as a novel group of layered van der Waals materials because of their exceptional physical properties and potential technological applications. Here, the epitaxial growth and stacking sequences of InTe is reported, an essential and intriguing material from III-VI metal chalcogenides. Aberration-corrected scanning transmission electron microscopy (STEM) is utilized to directly reveal the interlayer stacking modes and atomic structure, leading to a discussion of a new polytype. Furthermore, correlations between the stacking sequences and interlayer distances are substantiated by atomic-resolution STEM analysis, which offers evidence for strong interlayer coupling of the new polytype. It is proposed that layer-by-layer deposition is responsible for the formation of the unconventional stacking order, which is supported by ab initio density functional theory calculations. The results thus establish molecular beam epitaxy as a viable approach for synthesizing novel polytypes. The experimental validation of the InTe polytype here expands the family of materials in the III-VI metal chalcogenides while suggesting the possibility of new stacking sequences for known materials in this system.

Current Status of Flow Cytometric Immunophenotyping of Hematolymphoid Neoplasms in Korea.

Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCI-HLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey. We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positive/negative criteria, and reporting. Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positive/negative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. Conclusions: This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Iridium-Cooperated, Symmetry-Broken Manganese Oxide Nanocatalyst for Water Oxidation.

The water oxidation reaction, the most important reaction for hydrogen production and other sustainable chemistry, is efficiently catalyzed by the Mn4CaO5 cluster in biological photosystem II. However, synthetic Mn-based heterogeneous electrocatalysts exhibit inferior catalytic activity at neutral pH under mild conditions. Symmetry-broken Mn atoms and their cooperative mechanism through efficient oxidative charge accumulation in biological clusters are important lessons but synthesis strategies for heterogeneous electrocatalysts have not been successfully developed. Here, we report a crystallographically distorted Mn-oxide nanocatalyst, in which Ir atoms break the space group symmetry from I41/amd to P1. Tetrahedral Mn(II) in spinel is partially replaced by Ir, surprisingly resulting in an unprecedented crystal structure. We analyzed the distorted crystal structure of manganese oxide using TEM and investigated how the charge accumulation of Mn atoms is facilitated by the presence of a small amount of Ir.

Time-reversal symmetry breaking superconductivity between twisted cuprate superconductors.

Twisted interfaces between stacked van der Waals (vdW) cuprate crystals present a platform for engineering superconducting order parameters by adjusting stacking angles. Using a cryogenic assembly technique, we construct twisted vdW Josephson junctions (JJs) at atomically sharp interfaces between Bi2Sr2CaCu2O8+x crystals, with quality approaching the limit set by intrinsic JJs. Near 45° twist angle, we observe fractional Shapiro steps and Fraunhofer patterns, consistent with the existence of two degenerate Josephson ground states related by time-reversal symmetry (TRS). By programming the JJ current bias sequence, we controllably break TRS to place the JJ into either of the two ground states, realizing reversible Josephson diodes without external magnetic fields. Our results open a path to engineering topological devices at higher temperatures.

Pulsed-Mode Metalorganic Vapor-Phase Epitaxy of GaN on Graphene-Coated c-Sapphire for Freestanding GaN Thin Films.

We report the growth of high-quality GaN epitaxial thin films on graphene-coated c-sapphire substrates using pulsed-mode metalorganic vapor-phase epitaxy, together with the fabrication of freestanding GaN films by simple mechanical exfoliation for transferable light-emitting diodes (LEDs). High-quality GaN films grown on the graphene-coated sapphire substrates were easily lifted off by using thermal release tape and transferred onto foreign substrates. Furthermore, we revealed that the pulsed operation of ammonia flow during GaN growth was a critical factor for the fabrication of high-quality freestanding GaN films. These films, exhibiting excellent single crystallinity, were utilized to fabricate transferable GaN LEDs by heteroepitaxially growing InxGa1-xN/GaN multiple quantum wells and a p-GaN layer on the GaN films, showing their potential application in advanced optoelectronic devices.

Mucosal and systemic immune responses after a single intranasal dose of nanoparticle and spore-based subunit vaccines in mice with pre-existing lung mycobacterial immunity.

Tuberculosis (TB) is a major global health threat that claims more than one million lives annually. With a quarter of the global population harbouring latent TB, post-exposure vaccination aimed at high-risk populations that could develop active TB disease would be of great public health benefit. Mucosal vaccination is an attractive approach for a predominantly lung disease like TB because it elicits both local and systemic immunity. However, the immunological consequence of mucosal immunisation in the presence of existing lung immunity remains largely unexplored. Using a mycobacterial pre-exposure mouse model, we assessed whether pre-existing mucosal and systemic immune responses can be boosted and/or qualitatively altered by intranasal administration of spore- and nanoparticle-based subunit vaccines. Analysis of lung T cell responses revealed an increasing trend in the frequency of important CD4 and CD8 T cell subsets, and T effector memory cells with a Th1 cytokine (IFNγ and TNFα) signature among immunised mice. Additionally, significantly greater antigen specific Th1, Th17 and IL-10 responses, and antigen-induced T cell proliferation were seen from the spleens of immunised mice. Measurement of antigen-specific IgG and IgA from blood and bronchoalveolar lavage fluid also revealed enhanced systemic and local humoral immune responses among immunised animals. Lastly, peripheral blood mononuclear cells (PBMCs) obtained from the TB-endemic country of Mozambique show that individuals with LTBI showed significantly greater CD4 T cell reactivity to the vaccine candidate as compared to healthy controls. These results support further testing of Spore-FP1 and Nano-FP1 as post-exposure TB vaccines.

Single-crystalline GaN microdisk arrays grown on graphene for flexible micro-LED application.

We report the growth of single-crystalline GaN microdisk arrays on graphene and their application in flexible light-emitting diodes (LEDs). Graphene layers were directly grown onc-sapphire substrates using chemical vapor deposition and employed as substrates for GaN growth. Position-controlled GaN microdisks were laterally overgrown on the graphene layers with a micro-patterned SiO2mask using metal-organic vapor-phase epitaxy. The as-grown GaN microdisks exhibited excellent single crystallinity with a uniform in-plane orientation. Furthermore, we fabricated flexible micro-LEDs by achieving heteroepitaxial growth ofn-GaN, InxGa1-xN/GaN multiple quantum wells, andp-GaN layers on graphene-coated sapphire substrates. The GaN micro-LED arrays were successfully transferred onto bendable substrates and displayed strong blue light emission under room illumination, demonstrating their potential for integration into flexible optoelectronic devices.

Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer.

Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.