DGAT2 Plays a Crucial Role to Control ESRRAPROX1 Transcriptional Network to Maintain Hepatic Mitochondrial Sustainability.

Background: Diacylglycerol O-acyltransferase 2 (DGAT2) synthesizes triacylglycerol (TG) from diacylglycerol; therefore, DGAT2 is considered as a therapeutic target for steatosis. However, the consequence of inhibiting DGAT2 is not fully investigated due to side effects including lethality and lipotoxicity. In this article, we observed the role of DGAT2 in hepatocarcinoma. Methods: The role of DGAT2 is analyzed via loss-of-function assay. DGAT2 knockdown (KD) and inhibitor treatment on HepG2 cell line was analyzed. Cumulative analysis of cell metabolism with bioinformatic data were assessed, and further compared with different cohorts of liver cancer patients and non-alcoholic fatty liver disease (NAFLD) patients to elucidate how DGAT2 is regulating cancer metabolism. Results: Mitochondrial function is suppressed in DGAT2 KD HepG2 cell along with the decreased lipid droplets. In the aspect of the cancer, DGAT2 KD upregulates cell proliferation. Analyzing transcriptome of NAFLD and hepatocellular carcinoma (HCC) patients highlights negatively correlating expression patterns of 73 lipid-associated genes including DGAT2. Cancer patients with the lower DGAT2 expression face lower survival rate. DGAT2 KD cell and patients' transcriptome show downregulation in estrogen- related receptor alpha (ESRRA) via integrated system for motif activity response analysis (ISMARA), with increased dimerization with corepressor prospero homeobox 1 (PROX1). Conclusion: DGAT2 sustains the stability of mitochondria in hepatoma via suppressing ESRRA-PROX1 transcriptional network and hinders HCC from shifting towards glycolytic metabolism, which lowers cell proliferation.

Prognostic prediction of sepsis patient using transformer with skip connected token for tabular data.

Sepsis is known as a common syndrome in intensive care units (ICU), and severe sepsis and septic shock are among the leading causes of death worldwide. The purpose of this study is to develop a deep learning model that supports clinicians in efficiently managing sepsis patients in the ICU by predicting mortality, ICU length of stay (>14 days), and hospital length of stay (>30 days). The proposed model was developed using 591 retrospective data with 16 tabular data related to a sequential organ failure assessment (SOFA) score. To analyze tabular data, we designed the modified architecture of the transformer that has achieved extraordinary success in the field of languages and computer vision tasks in recent years. The main idea of the proposed model is to use a skip-connected token, which combines both local (feature-wise token) and global (classification token) information as the output of a transformer encoder. The proposed model was compared with four machine learning models (ElasticNet, Extreme Gradient Boosting [XGBoost]), and Random Forest) and three deep learning models (Multi-Layer Perceptron [MLP], transformer, and Feature-Tokenizer transformer [FT-Transformer]) and achieved the best performance (mortality, area under the receiver operating characteristic (AUROC) 0.8047; ICU length of stay, AUROC 0.8314; hospital length of stay, AUROC 0.7342). We anticipate that the proposed model architecture will provide a promising approach to predict the various clinical endpoints using tabular data such as electronic health and medical records.

Effect of Injectable Acellular Adipose Matrix on Soft Tissue Reconstruction in a Murine Model.

BACKGROUND: The extracellular matrix isolated from adipose tissue, known as acellular adipose matrix (AAM), represents a novel biomaterial. AAM functions as a scaffold that not only supports stem cell proliferation and differentiation but also induces adipogenesis and angiogenesis. This study aims to investigate the volumetric effects and microenvironmental changes associated with injectable AAM in comparison to conventional fat grafting. METHODS: AAM was manufactured from fresh human abdominoplasty fat using a mechanically modified method and then transformed into an injectable form. Lipoaspirate was harvested employing the Coleman technique. A weight and volume study was conducted on athymic nude mice by injecting either injectable AAM or lipoaspirate into the scalp (n=6 per group). After eight weeks, graft retention was assessed through weight measurement and volumetric analysis using micro-computed tomography (micro-CT) scanning. Histological analysis was performed using immunofluorescence staining for perilipin and CD31. RESULTS: Injectable AAM exhibited similar weight and volume effects in murine models. Histological analysis revealed comparable inflammatory cell presence with minimal capsule formation when compared to conventional fat grafts. Adipogenesis occurred in both AAM-injected and conventional fat graft models, with no significant difference in the blood vessel area (%) between the two. CONCLUSIONS: In summary, injectable AAM demonstrates effectiveness comparable to conventional fat grafting concerning volume effects and tissue regeneration in soft tissue reconstruction. This promising allogeneic injectable holds the potential to serve as a safe and effective "Off-the-Shelf" alternative in both aesthetic and reconstructive clinical practices. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Development and Evaluation of a Virtual Reality Simulator for Spinal Cord Stimulation: A Randomized Controlled Trial.

Purpose: The aim of this prospective study was to develop a virtual reality simulator (VRS) for spinal cord stimulation (SCS) trials and establish its effectiveness. Methods: We developed a VRS for SCS training by integrating patient imaging data analytics, creating artificial X-ray images, and using spatial alignment techniques and virtual reality technologies. The simulator was created by a physician with considerable experience in performing SCS, and can simulate the feeling of the procedure in a virtual environment. The efficacy of the simulator for SCS trials was assessed using a cohort of 20 novice trainees. The primary outcomes were duration of the procedure, checklist score, number of C-arm images captured, and overall trainee satisfaction. Results: The cohort that utilized the VRS had better Zwisch scale scores (P <0.001), completed the procedure in a shorter time (P <0.001), took fewer C-arm images (P <0.001), and reported better overall satisfaction (P = 0.011) than the cohort that did not. Conclusion: We developed a realistic and efficient VRS for educating novice trainees on SCS trials, thereby eliminating the risk of radiation exposure associated with cadaver training. The results of this study indicate that our VRS has potential as an instrumental resource that can be integrated into the educational framework for SCS trials.

Explainable artificial intelligence for predicting red blood cell transfusion in geriatric patients undergoing hip arthroplasty: Machine learning analysis using national health insurance data.

This study uses machine learning and population data to analyze major determinants of blood transfusion among patients with hip arthroplasty. Retrospective cohort data came from Korea National Health Insurance Service claims data for 19,110 patients aged 65 years or more with hip arthroplasty in 2019. The dependent variable was blood transfusion (yes vs no) in 2019 and its 31 predictors were included. Random forest variable importance and Shapley Additive Explanations were used for identifying major predictors and the directions of their associations with blood transfusion. The random forest registered the area under the curve of 73.6%. Based on random forest variable importance, the top-10 predictors were anemia (0.25), tranexamic acid (0.17), age (0.16), socioeconomic status (0.05), spinal anesthesia (0.05), general anesthesia (0.04), sex (female) (0.04), dementia (0.03), iron (0.02), and congestive heart failure (0.02). These predictors were followed by their top-20 counterparts including cardiovascular disease, statin, chronic obstructive pulmonary disease, diabetes mellitus, chronic kidney disease, peripheral vascular disease, liver disease, solid tumor, myocardial infarction and hypertension. In terms of max Shapley Additive Explanations values, these associations were positive, e.g., anemia (0.09), tranexamic acid (0.07), age (0.09), socioeconomic status (0.05), spinal anesthesia (0.05), general anesthesia (0.04), sex (female) (0.02), dementia (0.03), iron (0.04), and congestive heart failure (0.03). For example, the inclusion of anemia, age, tranexamic acid or spinal anesthesia into the random forest will increase the probability of blood transfusion among patients with hip arthroplasty by 9%, 7%, 9% or 5%. Machine learning is an effective prediction model for blood transfusion among patients with hip arthroplasty. The high-risk group with anemia, age and comorbid conditions need to be treated with tranexamic acid, iron and/or other appropriate interventions.

Outcomes of distal biceps repair at two-year follow-up.

PURPOSE: This single-centre study aimed to review the postoperative outcomes of distal biceps avulsion repair using a single incision with the endo-button technique. METHODS: A retrospective cohort study was performed of a single surgeon series of distal biceps repairs performed consecutively from September 2016 to September 2020. At two years, outcome measures included Oxford Elbow Score (OES), range of movement (ROM), complications and ongoing issues. RESULTS: Forty-five distal biceps tendon repairs were performed on 43 patients with a mean follow-up of 3.2 years (1.1-5.3). The average OES was 46 (11-48), and 90% of patients recovered a comparable range of movement to the contralateral side. Two patients developed re-rupture (4%) on days 0 and 9 of surgery, but there were no late re-ruptures of the repair. CONCLUSION: Short-term outcomes from distal biceps tendon repair show low complication rates, high patient satisfaction and good functional outcomes. The results would support acute surgical treatment of active, working-age, patients with distal biceps tendon ruptures.

Creeping fat exhibits distinct Inflammation-specific adipogenic preadipocytes in Crohn's disease.

Creeping fat (CrF) is an extraintestinal manifestation observed in patients with Crohn's disease (CD). It is characterized by the accumulation of mesenteric adipose tissue (MAT) that wraps around the intestinal wall. Although the role of CrF in CD is still debated, multiple studies have highlighted a correlation between CrF and inflammation, as well as fibrostenosais of the intestine, which contributes to the worsening of CD symptoms. However, the mechanism underlying the potential role of CrF in the development of Crohn's fibrosis remains an enigma. This study aimed to analyze CrF comprehensively using single-cell RNA sequencing analysis. The data was compared with transcriptomic data from adipose tissue in other disease conditions, such as ulcerative colitis, lymphedema, and obesity. Our analysis classified two lineages of preadipocyte (PAC) clusters responsible for adipogenesis and fibrosis in CrF. Committed PACs in CrF showed increased cytokine expression in response to bacterial stimuli, potentially worsening inflammation in patients with CD. We also observed an increase in fibrotic activity in PAC clusters in CrF. Co-analyzing the data from patients with lymphedema, we found that pro-fibrotic PACs featured upregulated pentraxin-3 expression, suggesting a potential target for the treatment of fibrosis in CrF. Furthermore, PACs in CrF exhibited a distinct increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as CCL, LIGHT, PDGF, MIF, and SEMA3. Interestingly, these interactions also increased in PACs of the lymphedema, whereas the increased MIF signal of PACs was found to be a distinct characteristic of CrF. In immune cell clusters in CrF, we observed high immune activity of pro-inflammatory macrophages, antigen-presenting macrophages, B cells, and IgG+ plasma cells. Finally, we have demonstrated elevated IgG+ plasma cell infiltration and increased pentraxin-3 protein levels in the fibrotic regions of CrF in CD patients when compared to MAT from both UC patients and healthy individuals. These findings provide new insights into the transcriptomic features related to the inflammation of cells in CrF and suggest potential targets for attenuating fibrosis in CD.

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.

Challenge for Trade-Off Relationship between the Mechanical Property and Healing Efficiency of Self-Healable Polyimide.

Polyimide is actively applied in various industrial fields because of its strong mechanical properties, owing to the interactions between the polymer chains. Fully aromatic imide structures exhibit high glass-transition temperatures due to the strong interactions between their chains, which hinder chain mobility. Therefore, preparing a material that exhibits self-healing at a low temperature of ≤100 °C and good mechanical properties is challenging. Thus, we prepared imides with four-component semiaromatic structures by adjusting the contents of 4,4'-(hexafluoroisopropylidene)diphthalic anhydride and 4,4'-(4,4'-isopropylidenediphenoxy)bis(phthalic anhydride) to yield four-component self-healable colorless polyimides (f-SH-CPIs) with novel structures, flexibilities, good mechanical properties, and low healing temperatures. The flexibilities and distances between the polymer chains, as the basis of the trade-off relationship between the mechanical properties and healing efficiency, were controlled. These materials may be used as substrates in wearable devices and multilayer insulation that may protect from space dust, cosmic rays, and satellite fragments.

Photothermal Lithography for Realizing a Stretchable Multilayer Electronic Circuit Using a Laser.

Photolithography is a well-established fabrication method for realizing multilayer electronic circuits. However, it is challenging to adopt photolithography to fabricate intrinsically stretchable multilayer electronic circuits fully composed of an elastomeric matrix, due to the opacity of thick stretchable nanocomposite conductors. Here, we present photothermal lithography that can pattern elastomeric conductors and via holes using pulsed lasers. The photothermal-patterned stretchable nanocomposite conductor exhibits 3 times higher conductivity (5940 S cm-1) and 5 orders of magnitude lower resistance change (R/R0 = 40) under a 30% strained 5000th cyclic stretch, compared to those of a screen-printed conductor, based on the percolation network formed by spatial heating of the laser. In addition, a 50 µm sized stretchable via holes can be patterned on the passivation without material ablation and electrical degradation of the bottom conductor. By repeatedly patterning the conductor and via holes, highly conductive and durable multilayer circuits can be stacked with layer-by-layer material integration. Finally, a stretchable wireless pressure sensor and passive matrix LED array are demonstrated, thus showing the potential for a stretchable multilayer electronic circuit with durability, high density, and multifunctionality.

Effects of Interfacial Electron Transport on Field Electron Emission from Carbon Nanotube Paste Emitters.

Field electron emission from carbon nanotubes (CNT) is preceded by the transport of electrons from the cathode metal to emission sites. Specifically, a supporting layer indispensable for adhesion of CNT paste emitters onto the cathode metal would impose a potential barrier, depending on its work function and interfacial electron transport behaviors. In this paper, we investigated the supporting layer of silicon carbide and nickel nanoparticles reacted onto a Kovar alloy (Fe-Ni-Co) cathode substrate, which has been adopted for reliable CNT paste emitters. The X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and electrical conductivity measurements showed that the reaction of silicon carbide and nickel nanoparticles on the Kovar metal strongly depends upon the post-vacuum-annealing conditions and can be classified into two procedures of a diffusion-induced reaction (DIR) and a diffusion-limited reaction (DLR). The prolonged annealing at 750 °C for 5 h before the main annealing of the CNT paste emitters at 800 °C for 5 min led to the DIR that has enhanced the Ni silicide phase and a lower potential barrier for the interfacial electron transport, resulting in increased and weakly temperature-dependent field electron emission from the CNT paste emitters. On the other hand, the DLR with only the main anneal of the CNT paste emitters at 800 °C for 5 min gave rise to a higher potential barrier for the electron transport and so lower and strongly temperature-dependent field electron emission. From the results of the interfacial electron transport for the DIR and DLR mechanisms in the CNT paste emitters, we concluded that the ambient temperature dependency of field electron emission from CNT tips in the moderate range of up to 400 °C, still controversial, is mainly attributed to the supporting layer of the CNT emitter rather than its intrinsic electron emission.

Gene signature from cutaneous autoimmune diseases provides potential immunotherapy-relevant biomarkers in melanoma.

Immune checkpoint inhibitors (ICIs) are promising agents for treating melanoma. Given that autoimmune skin diseases exhibit hyper immune reaction, investigation of immune cells from autoimmune skin disease is crucial to validate the effectiveness of ICIs in melanoma treatment. We employed multipanel markers to predict the response to immune checkpoint inhibitors by characterizing the gene expression signatures of skin immune cells in systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis (PS). By analyzing single-cell RNA sequencing data from each dataset, T cell gene signatures from autoimmune skin diseases exhibit a complex immune response in tumors that responded to immunotherapy. Based on that CD86 and CD80 provide essential costimulatory signals for T cell activation, we observed that interaction of CD86 signaling has been enhanced in the T cells of patients with SLE, AD, and PS. Our analysis revealed a common increase in CD86 signals from dendritic cells (DCs) to T cells in patients with SLE, AD, and PS, confirming that dendritic cells produce pro-inflammatory cytokines to activate T cells. Thus, we hypothesize that T cell gene signatures from autoimmune skin diseases exhibit a pro-inflammatory response and have the potential to predict cancer immunotherapy. Our study demonstrated that T cell gene signatures derived from inflammatory skin diseases, particularly SLE and PS, hold promise as potential biomarkers for predicting the response to immune checkpoint blockade therapy in patients with melanoma. Our data provide an understanding of the immune-related characteristics and differential gene expression patterns in autoimmune skin diseases, which may represent promising targets for melanoma immunotherapy.

Enhancement of Isotropic Heat Dissipation of Polymer Composites by Using Ternary Filler Systems Consisting of Boron Nitride Nanotubes, h-BN, and Al2O3.

In this research article, a poly(dimethylsiloxane) (PDMS)-based composite was postulated adapting an interactive ternary filler system consisting of Al2O3, hexagonal boron nitride (h-BN), and boron nitride nanotubes (BNNT) to construct a continuous three-dimensional (3D) structure for thermal attenuation. Al2O3 was imposed as a main filler, while h-BN and BNNT were assimilated to form interconnected heat conduction pathways for effective thermal dissipation. The structured framework articulates a profound improvement in isotropic thermal conductivity considering both axial and radial heat dissipation. The presence of h-BN entails uniform heat distribution in a planar mode, eliminating the occurrence of hotspots, while BNNT constructed a connecting phonon pathway in various directions, which insinuates effective overall thermal transport. The generated ternary filler composites attained an isotropic ratio of 1.35 and a thermal conductivity of 7.50 W/mK, which is a 36-fold (∼3650%) increase compared to neat PDMS resin and almost 3-fold (∼297%) that of the Al2O3 unary filler composite and ∼53% that of its binary counterpart, partaking interfacial thermal gaps of ∼36.15 and ∼62.24% on practical heating performance relative to its counterparts. Moreover, the incorporation of BNNT on a traditional spherical and planar filler offers an advantage not only in thermal conductivity but also in thermal and structural stability. Improvement in thermal stability is stipulated due to a melting point (Tm) shift of ∼11 °C upon the assimilation of BNNT. Mechanical permeance reinforcement was also observed with the presence of BNNT, showcasing a 31.5% increase in tensile strength and a 53% increase in Young's modulus relative to the singular filler composite. This exploration administers a new insight into heat dissipation phenomena in polymeric composites and proposes a simple approach to their design and assembly.

Porcine-specific expression of the three functional CYP19 paralogs in early conceptus, placenta, and gonads.

In brief: Aromatase catalyzes the synthesis of estrogens and has been shown to have an important role during the establishment of pregnancy in the pig. This study confirmed the differential expression of the three aromatase isoforms. Abstract: Although three porcine aromatase isoforms have been identified, their gene expression profiles in reproduction are still poorly understood. Here, we identified by Sanger sequencing unique nucleotide signatures for the three paralogous copies of Cyp19 and analyzed by RT-PCR the occurrence of the Cyp19 and Cyp17a1 transcripts at different tissues and stages of conceptus and fetal-placental development. Cyp19a1 and Cyp19a3 expressions were detected in conceptuses and gonads, respectively. Cyp19a2 transcripts were identified on both the conceptuses and the placenta samples. Transcripts for Cyp17a1 were detected predominantly in conceptus and gonads. In the endometrium of day 21 pregnant females, as well as days 12 and 17 pseudopregnant females, we did not detect the expression of Cyp19a1, Cyp19a2, or Cyp19a3. In our study, we have demonstrated distinct transcriptional regulation for the three functional Cyp19 paralogs and a potential role for Cyp17a1 in controlling the secretion of estrogen from the conceptus and the placenta.

FT-GAT: Graph neural network for predicting spontaneous breathing trial success in patients with mechanical ventilation.

BACKGROUND AND OBJECTIVES: Intensive care unit (ICU) physicians perform weaning procedures considering complex clinical situations and weaning protocols; however, liberating critical patients from mechanical ventilation (MV) remains challenging. Therefore, this study aims to aid physicians in deciding the early liberation of patients from MV by developing an artificial intelligence model that predicts the success of spontaneous breathing trials (SBT). METHODS: We retrospectively collected data of 652 critical patients (SBT success: 641, SBT failure: 400) who received MV at the Chungbuk National University Hospital (CBNUH) ICU from July 2020 to July 2022, including mixed and trauma ICUs. Patients underwent SBTs according to the CBNUH weaning protocol or physician's decision, and SBT success was defined as extubation performed by the physician on the SBT day. Additionally, our dataset comprised 11 numerical and 2 categorical features that can be obtained for any ICU patient, such as vital signs and MV setting values. To predict SBT success, we analyzed tabular data using a graph neural network-based approach. Specifically, the graph structure was designed considering feature correlation, and a novel deep learning model, called feature tokenizer graph attention network (FT-GAT), was developed for graph analysis. FT-GAT transforms the input features into high-dimensional embeddings and analyzes the graph via the attention mechanism. RESULTS: The quantitative evaluation results indicated that FT-GAT outperformed conventional models and clinical indicators by achieving the following model performance (AUROC): FT-GAT (0.80), conventional models (0.69-0.79), and clinical indicators (0.65-0.66) CONCLUSIONS: Through timely detection critical patients who can succeed in SBTs, FT-GAT can help prevent long-term use of MV and potentially lead to improvement in patient outcomes.

Epigenomic landscape exhibits interferon signaling suppression in the patient of myocarditis after BNT162b2 vaccination.

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-α/γ in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination.

Anti-Leukemic Effects of Idesia polycarpa Maxim Branch on Human B-Cell Acute Lymphoblastic Leukemia Cells.

Patients with pediatric B-cell acute lymphoblastic leukemia (B-ALL) have a high survival rate, yet the prognosis of adults and patients with relapsed/refractory disease is relatively poor. Therefore, it is imperative to develop new therapeutic strategies. Here, we screened 100 plant extracts from South Korean Flora and investigated their anti-leukemic effect using CCRF-SB cells as a B-ALL model. The top cytotoxic extract identified in this screening was the Idesia polycarpa Maxim. branch (IMB), which efficiently inhibited the survival and proliferation of CCRF-SB cells, while having minimal to no impact on normal murine bone marrow cells. Mechanistically, the IMB-induced proapoptotic effect involves the increase of caspase 3/7 activity, which was shown to be associated with the disruption of the mitochondrial membrane potential (MMP) through the reduction in antiapoptotic Bcl-2 family expression. IMB also promoted the differentiation of CCRF-SB cells via the upregulation of the expression of differentiation-related genes, PAX5 and IKZF1. Given that resistance to glucocorticoid (GC) is often found in patients with relapsed/refractory ALL, we investigated whether IMB could restore GC sensitivity. IMB synergized GC to enhance apoptotic rate by increasing GC receptor expression and downmodulating mTOR and MAPK signals in CCRF-SB B-ALL cells. These results suggest that IMB has the potential to be a novel candidate for the treatment of B-ALL.

PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress.

Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients.

Smart Materials with Dual Functionality: Repeatable Damage-Detection and Self-Healing.

Polymer materials are extensively used because of their excellent performance; however, when used for a long time, they break and eventually lose their original properties. Thus, smart polymer materials that can repeatedly detect and repair damage must be urgently developed to increase their durability and lifespan. In this study, a smart material with dual functionality (damage-detection and self-healing) is developed via a facile method of incorporating spiropyran (SP) beads, which exhibit changes in color and fluorescence when damaged, into a Diels-Alder (DA)-based self-healing matrix. When polyurethane (PU) is added to the DA-based matrix, the dual functionality exhibits a strong dependence on the proportion of PU. Because the PU ratio affects two opposing factors (damaged area and load-bearing capacity), the damage-detecting ability exhibits the best performance at 40 wt % PU, where both factors are optimized. A high healing efficiency of 96% is achieved via a dynamic DA reaction. In particular, the repeatability of the dual-functionality is successfully attained through the reversibility of the SP beads and DA networks, where the detection and healing efficiencies are reduced by 15 and 23%, respectively, after 10 cycles. Furthermore, the reprocessed fractured specimens exhibit excellent recyclability.