e20720 Background: Chemotherapy resistance remains a major clinical challenge, leading to treatment failure and disease relapse. Although protein acetylation is known to regulate cancer cell survival, the role of mitochondrial acetylation signaling in chemotherapy resistance is poorly understood. Here, we found the novel non-canonical function of mitochondrial dihydrolipoyl transacetylase (DLAT) in regulating chemotherapy response. Methods: An acetylome-focused RNA interference screen was performed to identify acetylation-related regulators of cisplatin resistance. Mechanistic studies included interaction proteomics, mutational analyses, metabolic profiling, and mitochondrial functional assays. Clinical relevance was assessed using tumor specimens from patients treated with chemotherapy or chemoimmunotherapy. The therapeutic potential of a decoy peptide (DMp39) targeting DLAT-MTHFD2 was evaluated in cell line- and patient-derived xenograft (PDX) mouse models. Results: DLAT was identified as a key driver of chemotherapy resistance across multiple cancer types. DLAT directly acetylated methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) at lysine 44, activating tetrahydrofolate metabolism by increasing 10-formyl-tetrahydrofolate levels. This metabolic rewiring induces expression of mitochondrial-encoded cytochrome c oxidase II (MT-CO2), reduces chemotherapy-induced mitochondrial reactive oxygen species, and promotes cancer cell survival during chemotherapy. Elevated DLAT signaling, including MTHFD2 acetylation, was observed in tumors from patients refractory to chemotherapy or chemoimmunotherapy. A decoy peptide, DMp39, which competes with MTHFD2 for acetylation by DLAT, was designed. DMp39 restored chemotherapy sensitivity and significantly suppressed tumor growth in PDX models without overt toxicity. Conclusions: Our study identifies a DLAT-MTHFD2 acetylation axis that mediates mitochondrial metabolic reprogramming as a critical mediator of chemotherapy resistance. Targeting this pathway with the unique decoy peptide DMp39 represents a promising therapeutic strategy to overcome resistance and enhance chemotherapy outcomes.
The wall-spandrel structural system is a common lateral force-resisting system in high-rise residential buildings in Korea. In this system, ductile behavior under seismic loading can be achieved by designing the spandrels to be weaker than the connecting walls. Although proper seismic detailing is critical, reinforcement detailing for deep, narrow wall spandrels can present challenges to constructability. Thus, this study proposes prefabricated reinforcement details for wall spandrels to facilitate on-site construction and experimentally evaluates the seismic performance. Cyclic tests were performed on seven wall spandrels with prefabricated or conventional reinforcement. The results showed that the wall spandrels with the prefabricated reinforcement exhibited strength and stiffness comparable to those with conventional reinforcement. However, due to premature concrete failure and reinforcement buckling/rupture in the minimally reinforced zone, their deformation capacities decreased to drift levels of 2 ~ 3%. The cyclic curves were significantly pinched, due to the small aspect ratios of 1.33 and 1.78, leading to limited hysteretic energy dissipation. The flexural and shear strengths of the wall spandrels were compared with the nominal strengths calculated according to conventional design theory. In addition, the effective stiffness prior to yielding and the deformation capacity, obtained from the experiments, were compared with the modeling parameters of coupling beams specified in existing seismic guidelines.
To enhance the progressive collapse resistance of precast concrete (PC) frames with pinned-joint, various strengthening details have been studied. However, many existing strengthening details can reduce the practical advantages of PC pinned joints by requiring complicated connection details. Thus, it is necessary to propose a new strengthening detail for pinned joints that overcome the limitations of existing details and enhance the progressive collapse resistance. In this study, four moment frame specimens with pinned joints were tested under monotonic vertical loading to investigate the effect of strengthening details (i.e., embedded tendons, exterior tendons, and penetrating tendons) on their progressive collapse behavior. The test results showed that the load-transfer mechanisms were significantly governed by the tendon anchorage of strengthening details. The overall progressive collapse resistance was contributed by the combined action of restraint and stiffness in compressive arch action (CAA) and increased tensile force in catenary action (CTA) due to tendons. These mechanisms were strongly influenced by continuity of strengthening details. In particular, SPC-P-2 with the exterior tendon exhibited a 161% higher measured PCTA than the control specimen before unintended anchorage failure occurred in the exterior anchorage device. The existing nominal strength model was modified by incorporating the tendon contribution of the strengthening details. The predicted-to-experimental strength ratios ranged from 0.94 to 1.16 for CAA and 0.92 to 1.32 for CTA, indicating that the proposed strength model can reasonably estimate the CAA and CTA strengths of the test specimens within the adopted specimen configuration and boundary conditions. The contribution of strengthening details with tendon to the CAA and CTA strength of the test specimens was evaluated using the proposed model. Further, a parametric study was performed to investigate the effects of beam depth (with the same rebar ratio), beam span, tendon ratio, and bracket length. Based on the test and parametric study results, design recommendations for strengthening details to enhance progressive collapse resistance were discussed.
After large earthquakes, rapid recovery of damaged buildings is essential to minimize public inconvenience and ensure social resilience. This study investigated rapid recovery methods for earthquake-damaged reinforced concrete (RC) columns. Cyclic lateral loading tests were conducted on pre-damaged columns to validate two recovery techniques: FRP wrapping and the proposed steel channel units. As a test parameter, the damage levels were controlled using different residual drift ratios prior to repair. The reference column showed flexural-shear dominant behavior and failed due to diagonal tension cracking and rebar buckling. After recovery, both FRP wrapping and steel channel units induced the ductile flexural yielding of specimens. The load-carrying capacity, deformation capacity, and cumulative energy dissipation capacity of the recovered specimens increased compared to the original column. Higher damage level decreased the recovery rates of effective stiffness due to increased crack widths and concrete spalling. Further, a damage index (DI)-based framework was proposed to quantify the damage level of RC columns using residual deformation measurable under post-earthquake conditions. The proposed approach provides a practical basis for post-earthquake decision-making and rapid recovery of damaged RC columns.
Abstract Oral squamous cell carcinoma (OSCC) frequently exhibits early locoregional recurrence despite adjuvant therapy. Circulating cell-free DNA (cfDNA) has emerged as a minimally invasive approach for evaluating tumor burden and disease dynamics. While most studies have focused on ctDNA mutations, the prognostic value of cfDNA fragmentomics—particularly mononucleosomal and dinucleosomal DNA—remains unclear in OSCC. Here, we investigated baseline cfDNA characteristics, mutational profiles, and fragmentation patterns, and evaluated their utility for recurrence prediction and longitudinal surveillance. Sixty-eight HPV-negative OSCC patients were prospectively enrolled, and plasma was collected at diagnosis and during follow-up. Baseline cfDNA was detected in 98.5% of patients (mean 6.65 μg/mL). Higher cfDNA levels correlated with aggressive clinical features, including advanced T stage, lymph node metastasis, and TNM III-IV disease, supporting its association with tumor burden. Targeted sequencing identified somatic variants in 30 genes, most commonly NOTCH1 (41%), FBXW7 (25%), and MGA (22%). Pathogenic variants were less frequent and did not correlate with TNM stage, and patients who recurred harbored fewer detectable mutations, indicating limited prognostic value of mutation-based profiling. Fragmentation analysis revealed distinct clinical implications for mono- and dinucleosomal cfDNA. Elevated baseline mononucleosomal cfDNA predicted recurrence, and a 3 ng/mL cutoff identified patients with significantly shorter recurrence-free survival. Dinucleosomal cfDNA, however, demonstrated superior value for longitudinal surveillance. Among 16 patients with locoregional recurrence, 13 (81%) showed detectable dinucleosomal cfDNA at or before radiologic confirmation, often during imaging-negative intervals. Persistent dinucleosomal cfDNA reflected ongoing local tumor activity, whereas metastatic recurrences rarely showed positivity. These results demonstrate that cfDNA fragmentomics provides prognostic information beyond mutation profiling in OSCC. Baseline mononucleosomal cfDNA stratifies patients at increased risk of recurrence, while the presence of dinucleosomal cfDNA offers a sensitive and clinically practical indicator of emerging locoregional disease. Together, these fragment-based biomarkers support the incorporation of cfDNA fragmentation analysis into postoperative surveillance strategies for earlier and more accurate detection of relapse. Citation Format: Jiyoung Lee, Mi Rim Lee, Sumin Kang, Jung-Ah Hwang, Hye Won Shon, Yu-Sun Lee, Sun Il Choi, Gyeongmin Kang, Jong-Ho Lee, Sun-Young Kong, Sung Weon Choi, Yun-Hee Kim. Fragmented plasma cfDNA as a prognostic and surveillance biomarker for locoregional recurrence in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7829.
Abstract Over 60% of patients with oral cancer are diagnosed at advanced stages, and the standard treatment was surgery followed by adjuvant radiotherapy. Nevertheless, 30-50% of patients experience recurrence within two years, whereas patients with radiosensitive tumors may be exposed to unnecessarily high radiation doses. Therefore, predicting radiotherapy response and stratifying patients is essential for personalized treatment approaches and improving clinical outcomes. Patient-derived organoids (PDOs) are robust preclinical models that recapitulate the characteristics of patients' tumors. In this study, we defined radiation sensitivity indicators using an oral cancer PDO library comprising 102 patient-derived organoids. Dose-dependent radiation responses were evaluated for 68 PDOs and correlated with clinical data. When organoids were classified based on the mean survival fraction at 2 Gy (SF2), patients in the high-SF2 group exhibited a significantly shorter recurrence-free survival. It suggests that PDO-based assessment of radiation response may serve as a useful predictor of clinical outcomes. In addition, a radiation sensitivity-related pathway score was generated from differentially expressed genes (DEGs) identified in radiosensitive PDOs and applied to The Cancer Genome Atlas (TCGA) oral cancer cohort. Patients were classified into low- and high-score groups according to the sensitivity score. The high-score group had a significantly more favorable survival prognosis. Furthermore, to identify a tissue-detectable radiation sensitivity marker (RSM), we selected the gene associated with the most enriched pathway in the low-SF2 organoid group, resulting in the identification of a candidate marker, RSM-1. Subsequent immunohistochemical (IHC) analysis demonstrated that RSM-1 was expressed at higher levels in tumors from patients without recurrence. Overall, this study utilized patient-derived organoids to evaluate radiation responses, derive a radiosensitivity score, and identify a clinically relevant biomarker. By integrating molecular and phenotypic tumor characteristics, this approach provides reliable prognostic indicators, enabling prediction of patients’ radiation responses and supporting personalized therapeutic strategies to improve prognosis in oral cancer. Citation Format: Sumin Kang, Mi Rim Lee, Jonghyun Lee, Dongkwan Shin, Jong-Ho Lee, Ikjae Kwon, Jiyoung Lee, Yu-Sun Lee, Sun-il Choi, Hye Won Shon, Gyeongmin Kang, Sung Woen Choi, Yun-Hee Kim. Defining radiosensitivity indicators to predict prognosis using patient-derived organoids in oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4642.
Current seismic design codes require complicated lateral confinement details for the boundary elements of reinforced concrete (RC) slender shear walls to secure the deformation capacity, which leads to deterioration of the workability and economy. In this study, pre-fabricated rectangular continuous hoops (PRCHs) were used as alternative lateral confinement details for wall boundary elements. As PRCHs are manufactured in factories, it is possible to enhance their workability and economy significantly compared with conventional lateral confinement details. To evaluate the compression capacity of the wall boundary elements confined with PRCHs, 10 specimens were tested under cyclic and monotonic axial loading. The type of lateral confinement, vertical and horizontal spacing of the PRCHs, and loading methods were addressed as test parameters. The test results showed that the boundary elements with PRCHs showed an equivalent ultimate deformation capacity compared with the boundary elements with special seismic details specified in the current design codes. Decrease of the vertical spacing of PRCHs from 75 mm to 50 mm increased effective confined compressive strength (f(cc)') by 13 % and the ultimate confined concrete strain (epsilon(cu,c)) by 26 %. In addition, increase of the net horizontal spacing between PRCH modules from 0 to 100 mm decreased f(cc)' by 8 %-13 % and epsilon(cu,c) by 5 %-12 %. To accurately evaluate the concrete confinement effect of PRCH, a modified stress-strain model was suggested based on the Mander's confinement model. Using the proposed method, the strength and deformation capacity of walls with confined by PRCHs were quantitatively compared to those of unconfined walls and walls with special seismic details.
Abstract Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with a recurrence rate of 40-60%, frequently exhibiting locoregional relapse and lymph node metastasis even after definitive treatment. Tumor progression and recurrence are driven not only by intrinsic characteristics of cancer cells but also by complex interactions with the surrounding tumor microenvironment (TME). To explore recurrence-associated regulatory pathways, we performed LC-MS/MS-based phosphoproteomic profiling of plasma from 34 OSCC patients and identified 113 phosphoproteins harboring 261 phosphosites enriched in lipid binding, complement activation, extracellular matrix (ECM) organization, and calcium-binding functions. Principal component and correlation analyses distinguished patients with recurrence from those without, and consensus clustering revealed three phospho-secretory subtypes. Notably, the subtype with the poor prognosis exhibited a enrichment of phospho-serine within the S-x-E motif. This pattern suggested activation of the secreted serine kinase FAM20C, which phosphorylates ER/Golgi-localized secretory proteins and membrane ectodomain substrates. Public datasets confirmed that high FAM20C expression correlates with increased recurrence risk and reduced overall and progression-free survival. To validate these findings, we examined patient-derived organoids (PDOs) and cancer-associated fibroblasts (CAFs) established from our cohort. Both FAM20C expression and secretion were markedly elevated in PDOs derived from recurrent tumors, and CAFs from recurrent patients also exhibited increased FAM20C secretion. Functionally, FAM20C overexpression enhanced invasion, ECM remodeling, and EMT activation, while FAM20C knockdown suppressed mesenchymal markers, reduced TGF-β-SMAD2/3 signaling, and suppressed stemness-associated genes including SOX2, OCT4, CD44, NANOG, MYC, and CD133. Together, these findings identify FAM20C as a key regulator of recurrence-associated extracellular signaling and highlight its potential as a prognostic biomarker for recurrence in OSCC. Citation Format: Mi Rim Lee, Yu-Sun Lee, Sumin Kang, Jiyoung Lee, Hye Won Shon, Sun Il Choi, Gyeongmin Kang, Kyung-Hee Kim, Jong-Ho Lee, Ik-Jae Kwon, Sung Woen Choi, Yun-Hee Kim. Extracellular kinome network reveals secretory kinase FAM20C as a key driver of recurrence in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7690.
Abstract Chemotherapy resistance remains a major obstacle in cancer treatment, leading to disease relapse and poor patient outcomes. Although protein acetylation is known to regulate diverse oncogenic processes, its role in therapeutic resistance is incompletely defined. Through an acetylome-based RNA interference screen, we identified mitochondrial dihydrolipoyl transacetylase (DLAT) as a key regulator of chemotherapeutic resistance. We found that DLAT promotes chemoresistance by controlling chemotherapy-induced ROS. Interaction proteomics and mutational analysis revealed that DLAT binds to and acetylates methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) at lysine 44, activating mitochondrial tetrahydrofolate metabolism and increasing 10-formyl-tetrahydrofolate levels. This metabolic rewiring induces expression of the mitochondrial-encoded cytochrome c oxidase II (MT-CO2) and enhances mitochondrial oxidative capacity, thereby supporting survival under chemotherapeutic stress. Analysis of clinical tumor specimens revealed elevated DLAT signaling in patients refractory to chemotherapy or chemoimmunotherapy, supporting the clinical relevance of the finding. Lastly, we developed a decoy peptide, DMp39, that specifically targets DLAT and MTHFD2 signaling, thereby restoring sensitivity to chemotherapy in patient-derived xenograft models and opening a new avenue for therapeutically targeting the crucial pathway involved in chemoresistance. These groundbreaking findings establish DLAT-driven mitochondrial acetylation signaling as a therapeutic vulnerability and provide a new type of therapy that can be combined with standard chemotherapy to benefit patients whose cancers have become resistant to the regimen. Citation Format: Jung Seok Hwang, Jaehyun Kim, Kiyoung Eun, Vanessa Avalos, Sydney Shuff, Margaret Stephens, Sumin Kang. Novel peptide decoy targeting mitochondrial dihydrolipoyl transacetylase-driven redox signaling to improve cancer chemotherapy outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB185.
Culvert slip lining restores deteriorated culverts by inserting a smaller-diameter HDPE liner and filling the annular space with grout to reestablish structural integrity. However, incomplete grouting can create voids that compromise load transfer and long-term performance. Existing inspection techniques provide limited or localized information, underscoring the need for a reliable non-destructive method to assess grouting integrity. This study investigates the use of high-frequency ground-penetrating radar (GPR) - operating up to 6 GHz- for detecting and quantifying voids within grouted annular spaces of lined culverts. The approach represents one of the first applications of high-resolution radar for this purpose and examines characteristic signal features such as amplitude attenuation, phase variation, and reflection signals, which are sensitive to discontinuities and material interfaces. Validation was achieved through a combination of numerical simulations, controlled laboratory experiments, and in-situ field measurements on rehabilitated culverts. Results from all three stages demonstrate that high-frequency GPR offers a reliable, non-destructive means to detect and characterize voids in culvert grout, enabling improved quality control, structural assessment, and maintenance planning. Voids identified by GPR in field trials were independently confirmed through endoscopic inspections.
Conventional reinforced concrete shear walls often exhibit severe damage and large residual deformation during earthquakes, making post-earthquake repair difficult and time-consuming. To improve seismic resilience and repairability, this study proposed two prefabricated self-centering shear wall systems using localized UHPC, replaceable wall-footing components, and post-tensioned tendons or pre-compressed disc spring devices. Cyclic analysis was conducted to evaluate the seismic performance of the specimens, both before and after repair, under staged loading conditions. The test results showed that both systems developed a controlled rocking response and effectively concentrated major damage in replaceable wall-footing components, thereby reducing residual deformation. Following localized repair and component replacement, the repaired-stage specimens regained most of their initial lateral load-carrying capacity and stiffness, thereby validating the efficacy of the repairable wall-footing design. Among the two systems, the tendon-based wall demonstrated higher lateral load-carrying capacity and energy dissipation, while the disc spring-based wall exhibited lower residual displacement and better recentering performance. Furthermore, a mechanics-based analytical model was developed for squat selfcentering walls (aspect ratio <= 2.0), which showed good agreement with test results and outperformed current design code models.
Ferroptosis is an iron-catalyzed lipid peroxidation-dependent cell death that mediates the development of many diseases, including liver injury. Compelling evidence has suggested a crucial role of mitochondrial reactive oxygen species (mtROS) in the induction of ferroptosis, but the underlying mechanism remains poorly defined. In this study, the impact of mtROS-driven signaling on cellular metabolism, oxidation-reduction state, and ferroptosis vulnerability of the hepatocytes was investigated by using mtROS inducers, including iron overload and pharmacologic inducers. Elevations in mtROS production and lipid peroxidation suppressed glycolysis, fatty acid oxidation, and tricarboxylic acid cycle activity, protecting hepatocytes from ferroptosis. In contrast, mtROS-induced signaling down-regulated genes involved in glutathione biosynthesis, and coenzyme Q10 (CoQ) biosynthesis, including those in the mevalonate pathway, and CoQ8A, a key stabilizer of the CoQ biosynthetic complex. Importantly, silencing CoQ8A expression enhanced, whereas overexpression of CoQ8A reduced, ferroptosis susceptibility of the hepatocytes. Further analysis showed that mtROS-mediated down-regulation of CoQ8A is dependent on farnesoid X receptor and retinoid X receptor. Collectively, these findings suggest that mtROS induces down-regulation of glutathione and CoQ biosynthesis, thereby promoting ferroptotic death in hepatocytes.
The double beam system is a precast concrete moment-resisting frame system in which precast beam elements to support the floor slab pass alongside the column, rather than being directly connected to it. The precast beams are integrated with the column via the cast-in-place concrete joints and topping reinforced with on-site emulative reinforcement. In this study, the seismic performance of the double beam-to-column connections, emulating cast-in-place construction, was experimentally and analytically investigated. Cyclic tests showed that the double beam connections exhibited robust stiffness (prior to yielding) and strength, and maintained excellent deformation capacity, achieving lateral drift ratios exceeding 5% with post-peak gradual strength degradation. However, the joints between the precast beam and column elements experienced severe concrete damage, leading to pronounced pinching in the cyclic curves and a substantial reduction in energy dissipation capacity. The double beam connections satisfied the strength and deformability requirements of ACI 374.1–05 but did not meet the criteria for energy dissipation and unloading/reloading stiffness under cyclic hysteretic behavior at a drift ratio of 3.5%. The transfer of moments from the precast beams to the column through the cast-in-place joints with emulative reinforcement was further investigated using finite element analysis.
Incretin mimetics, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), have demonstrated unprecedented efficacy in obesity management. However, their primary mechanisms, such as appetite suppression and delayed gastric emptying, significantly reduce the total energy intake, which can lead to nutritional risks, including essential micronutrient deficiencies and reduced lean body mass, which negatively affects physical function and metabolic rate. This review examined nutritional management strategies to address these issues. This review proposes comprehensive management strategies that focus on preserving muscle health and nutritional status. This review introduces the concept of ‘Companion Food Systems’, an integrated nutritional strategy that coordinates nutrient-dense foods, strategic nutrient pairing, adjunctive nutritional support, and pharmacokinetic-tailored chrononutrition to maintain protein and micronutrient delivery within a reduced-intake setting. This integrated approach aims to support lean mass preservation and overall metabolic health during incretin mimetic-induced weight loss.
Although stone breakout failure governs the behavior of dowel-pinned stone connections, the mechanical properties and dimensions of the stone have not been addressed in design of dimension stone cladding. This study aimed to investigate the effects of stone properties on the structural behavior and capacity of connections by testing six types of granite with two different thicknesses. Standard breakout tests were conducted for dowel-pinned connections, considering parameters such as stone type, panel thickness, and the use of silicon injection at the dowel hole. The test results revealed that the breakout strength of the dowel-pinned connections tended to be linearly proportional to tensile-related strengths of granite as predicted by existing equations. While silicone injection at the dowel hole enhanced deformation capacity, it did not increase the breakout strength. However, with thicker stone panels, the breakout strength significantly increased by a factor of 3.05-6.43 due to deeper spall depth, resulting in a larger area of the rupture cone. Based on the breakout test results, a modified equation for the breakout strength of dowel-pinned connections, considering stone thickness, was proposed. The proposed model aligned well with the tested peak strength for both 30 mm and 50 mm thick stone panels across various material strengths.
Chemotherapy is often a primary treatment for cancer. However, resistance leads to therapeutic failure. Acetylation dynamics play important regulatory roles in cancer cells, but the mechanisms by which acetylation mediates therapy resistance remain poorly understood. Here, using acetylome-focused RNA interference (RNAi) screening, we find that acetylation induced by mitochondrial dihydrolipoyl transacetylase (DLAT), independent of the pyruvate dehydrogenase complex, is pivotal in promoting resistance to chemotherapeutics, such as cisplatin. Mechanistically, DLAT acetylates methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) at lysine 44 and promotes 10-formyl-tetrahydrofolate (10-formyl-THF) and consequent mitochondrially encoded cytochrome c oxidase II (MT-CO2) induction. DLAT signaling is elevated in cancer patients refractory to chemotherapy or chemoimmunotherapy. A decoy peptide DMp39, designed to target DLAT signaling, effectively sensitizes cancer cells to cisplatin in patient-derived xenograft models. Collectively, our study reveals the crucial role of DLAT in shaping chemotherapy resistance, which involves an interplay between acetylation signaling and metabolic reprogramming, and offers a unique decoy peptide technology to overcome chemotherapy resistance.
Advanced oral squamous cell carcinoma (OSCC) is an aggressive cancer with a recurrence rate of 40-60%, and lymph node metastasis (LNM) occurs in 50% of cases, serving as a critical prognostic factor. Recent evidence suggests that fatty acid oxidation (FAO) enhances cancer cell survival, invasiveness, and therapeutic resistance. OSCC's histological proximity to dense adipose tissue provides a unique opportunity for cancer cells to acquire energy from the adipose environment, underscoring the importance of elucidating the tumor-adipose interactions in OSCC progression and metastasis. In this study, we investigated the impact of the tumor-adipose microenvironment on OSCC progression, focusing on interactions between adipocytes and cancer cells. Human adipose-derived stem cells (ADSCs) were differentiated into adipocytes and co-cultured with the OSCC cell line YD10B for three weeks to induce cancer-associated adipocytes (CAAs). Co-cultured adipocytes exhibited fibroblast-like phenotypic changes, reduced expression of adipogenic differentiation markers, and increased free fatty acid release. Inflammatory cytokines (e.g., IL-6) and tumor-promoting proteins (e.g., IGFBP-2) were upregulated. YD10B cells exposed to co-cultured adipocytes showed enhanced proliferation, invasion, and epithelial-mesenchymal transition (EMT) signaling. Adipocytes and cancer cells both showed increased expression of matrix metalloproteinases (MMP-2 and MMP-9), indicating mutual reinforcement of tumor aggressiveness. Collectively, these findings indicate that adipocytes, through their interaction with OSCC cells, undergo changes to acquire a CAA-like phenotype , which support tumor progression by providing fatty acids as an energy source and promoting aggressive phenotypes, including proliferation, invasion, and LNM. Targeting tumor-adipocyte interactions could offer novel therapeutic strategies to mitigate OSCC progression and improve outcomes. Gyeongmin Kang, Mi Rim Lee, Sumin Kang, Yu-Sun Lee, Hye Won Shon, Jiyoung Lee, Sung Weon Choi, Sun Il Choi, Yun-Hee Kim. Tumor-adipose microenvironment drives progression in advanced oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5232.
In recent years, performance of concrete-filled steel tubular (CFST) short columns under axial compression after freeze-thaw cycles has gained attention for its long-term durability in colder climates. In the present study, freeze-thaw cycle test was conducted on the square section CFST (S-CFST) short columns to evaluate the influence of steel tube wall thickness and sectional dimension on the axial compression resistance of S-CFST short columns after freeze-thaw cycles. The infilled concrete strength degradation model and the calculation model for the axial compression resistance of the circular and square section CFST (C-CFST and S-CFST) short columns that can comprehensively consider design factors, such as the number of freeze-thaw cycles, concrete strength, and steel tube wall thickness, are proposed. Also, a parametric study is conducted to evaluate the accuracy and rationality of the prediction results of the existing models for concrete strength degradation and axial compression resistance of CFST short columns after freeze-thaw cycles. The existing experimental data and model parameter analysis indicate that as the steel tube wall thickness and concrete strength increased, the detrimental effects of freeze-thaw cycles on the in-filled concrete and the axial compression resistance of CFST short columns diminished significantly. The proposed model showed good accuracy and stability for predicting the axial compression resistance of C-CFST and S-CFST short columns after freeze-thaw cycles, without limitation of material strength range and the number of freeze-thaw cycles. Further, the infilled concrete strength degradation model was applicable to current design code models for the axial compression resistance of CFST short columns under normal temperature conditions, which estimated the axial compression resistance of CFST short columns after freeze-thaw cycles.
To enhance the seismic performance of precast concrete (PC) shear walls, integrating ultra-high performance concrete (UHPC) has emerged as a promising approach. In this study, three novel type of PC shear walls with partial use of UHPC were proposed to improve the seismic performance while satisfying economic feasibility. UHPC was partially applied to the boundary elements, X-shaped bracing, and two vertical columns in the PC wall panel. Three PC shear walls and a control shear wall cast in place were subjected to cyclic loading to evaluate the seismic performance. The crack development and failure modes, hysteretic behavior, deformation components, stiffness degradation, and energy dissipation capacity were analyzed and compared. Three novel PC shear walls exhibited superior seismic performance compared with cast-in-place shear wall. Compared with cast-in-place shear wall, the load-carrying capacity and ductility of three PC shear walls increased by 41.8-46.8 % and 27.9-66.5 %, respectively. The energy dissipation capacity of PC shear walls increased significantly, ranging from 81.8 to 201.2 %. Compared with PC shear wall using UHPC in the boundary element only, the PC shear wall with additional two vertical UHPC columns in the wall panel exhibited the greater load-carrying capacity, ductility, and energy dissipation capacity. The PC shear wall using additional X-shaped bracing exhibited the greatest initial and yield stiffness. Based on a strut-and-tie model, a design equation for shear strength of the proposed PC shear walls was derived. The predictions correlate well with the test results.