Single-cell RNA sequencing data imputation using bi-level feature propagation.

Single-cell RNA sequencing (scRNA-seq) enables the exploration of cellular heterogeneity by analyzing gene expression profiles in complex tissues. However, scRNA-seq data often suffer from technical noise, dropout events and sparsity, hindering downstream analyses. Although existing works attempt to mitigate these issues by utilizing graph structures for data denoising, they involve the risk of propagating noise and fall short of fully leveraging the inherent data relationships, relying mainly on one of cell-cell or gene-gene associations and graphs constructed by initial noisy data. To this end, this study presents single-cell bilevel feature propagation (scBFP), two-step graph-based feature propagation method. It initially imputes zero values using non-zero values, ensuring that the imputation process does not affect the non-zero values due to dropout. Subsequently, it denoises the entire dataset by leveraging gene-gene and cell-cell relationships in the respective steps. Extensive experimental results on scRNA-seq data demonstrate the effectiveness of scBFP in various downstream tasks, uncovering valuable biological insights.

Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion.

Ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury (AKI), is still without effective therapies. Succinate accumulation during ischemia followed by its oxidation during reperfusion leads to excessive reactive oxygen species (ROS) and severe kidney damage. Consequently, the targeting of succinate accumulation may represent a rational approach to the prevention of IR-induced kidney injury. Since ROS are generated primarily in mitochondria, which are abundant in the proximal tubule of the kidney, we explored the role of pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial enzyme, in IR-induced kidney injury using proximal tubule cell-specific Pdk4 knockout (Pdk4ptKO) mice. Knockout or pharmacological inhibition of PDK4 ameliorated IR-induced kidney damage. Succinate accumulation during ischemia, which is responsible for mitochondrial ROS production during reperfusion, was reduced by PDK4 inhibition. PDK4 deficiency established conditions prior to ischemia resulting in less succinate accumulation, possibly because of a reduction in electron flow reversal in complex II, which provides electrons for the reduction of fumarate to succinate by succinate dehydrogenase during ischemia. The administration of dimethyl succinate, a cell-permeable form of succinate, attenuated the beneficial effects of PDK4 deficiency, suggesting that the kidney-protective effect is succinate-dependent. Finally, genetic or pharmacological inhibition of PDK4 prevented IR-induced mitochondrial damage in mice and normalized mitochondrial function in an in vitro model of IR injury. Thus, inhibition of PDK4 represents a novel means of preventing IR-induced kidney injury, and involves the inhibition of ROS-induced kidney toxicity through reduction in succinate accumulation and mitochondrial dysfunction.

Integrative single-cell transcriptome analysis provides new insights into post-COVID-19 pulmonary fibrosis and potential therapeutic targets.

The global COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 virus has resulted in a significant number of patients experiencing persistent symptoms, including post-COVID pulmonary fibrosis (PCPF). This study aimed to identify novel therapeutic targets for PCPF using single-cell RNA-sequencing data from lung tissues of COVID-19 patients, idiopathic pulmonary fibrosis (IPF) patients, and a rat transforming growth factor beta-1-induced fibrosis model treated with antifibrotic drugs. Patients with COVID-19 had lower alveolar macrophage counts than healthy controls, whereas patients with COVID-19 and IPF presented with elevated monocyte-derived macrophage counts. A comparative transcriptome analysis showed that macrophages play a crucial role in IPF and COVID-19 development and progression, and fibrosis- and inflammation-associated genes were upregulated in both conditions. Functional enrichment analysis revealed the upregulation of inflammation and proteolysis and the downregulation of ribosome biogenesis. Cholesterol efflux and glycolysis were augmented in both macrophage types. The study suggests that antifibrotic drugs may reverse critical lung fibrosis mediators in COVID-19. The results help clarify the molecular mechanisms underlying pulmonary fibrosis in patients with severe COVID-19 and IPF and highlight the potential efficacy of antifibrotic drugs in COVID-19 therapy. Collectively, all these findings may have significant implications for the development of new treatment strategies for PCPF.

Balanced Free Essential Amino Acids and Resistance Exercise Training Synergistically Improve Dexamethasone-Induced Impairments in Muscle Strength, Endurance, and Insulin Sensitivity in Mice.

Our previous study shows that an essential amino acid (EAA)-enriched diet attenuates dexamethasone (DEX)-induced declines in muscle mass and strength, as well as insulin sensitivity, but does not affect endurance. In the present study, we hypothesized that the beneficial effects will be synergized by adding resistance exercise training (RET) to EAA, and diet-free EAA would improve endurance. To test hypotheses, mice were randomized into the following four groups: control, EAA, RET, and EAA+RET. All mice except the control were subjected to DEX treatment. We evaluated the cumulative rate of myofibrillar protein synthesis (MPS) using 2H2O labeling and mass spectrometry. Neuromuscular junction (NMJ) stability, mitochondrial contents, and molecular signaling were demonstrated in skeletal muscle. Insulin sensitivity and glucose metabolism using 13C6-glucose tracing during oral glucose tolerance tests were analyzed. We found that EAA and RET synergistically improve muscle mass and/or strength, and endurance capacity, as well as insulin sensitivity, and glucose metabolism in DEX-treated muscle. These improvements are accomplished, in part, through improvements in myofibrillar protein synthesis, NMJ, fiber type preservation, and/or mitochondrial biogenesis. In conclusion, free EAA supplementation, particularly when combined with RET, can serve as an effective means that counteracts the adverse effects on muscle of DEX that are found frequently in clinical settings.

Supporting free clinic patients' social needs with MSW interns: A pilot study.

Social needs, which are social risk factors including lack of access to stable housing, healthy food, or reliable transportation, are recognized as integral to health. Free clinics tend to serve patients with social needs, yet, few are screened or receive assistance. Lack of personnel, resources, and procedures to identify and assist patients are reasons few free clinics consider social needs. To address this service gap, a midwestern free clinic and neighboring Masters of Social Work (MSW) program established a partnership. A social needs screen was developed and integrated into health care practice. An MSW intern was also embedded as a member of the health care team to provide social needs assistance. A 6-month pilot study was conducted to assess the value of the screen and use of MSW assistance services. Of the 223 patients screened, 66.4% (n = 146) scored positive for social needs. Only four percent (n = 6) of the patients used MSW services. Chi-square analyses reveal significant differences in social needs by age, gender, race, education, and primary language. The findings suggest that the screening and MSW intern services are valuable; however, they further suggest that screening alone may be insufficient to encourage utilization of MSW services.

Further examination of knowledge and interactions in ageism among college students: Value for promoting university activities.

Ageism is recognized as a reason that few students pursue careers in aging. While widely studied, the findings regarding factors that contribute to ageism are mixed. The findings from previous studies are also tempered by methodological issues. To better understand the factors that contribute to ageism among students and guide the development of programming and activities to reduce ageism, a survey study was conducted. The study explores associations between frequency of interactions with older adults, quality of the interactions, and ageism. Students' knowledge of aging is also examined. Using refined measures to assess knowledge of aging and interactions with older adults, the study includes data from 1,040 college students, most of whom are traditional age students (i.e., under the age of 25). Findings from multiple regression analyses document the interplay between frequency and quality of interactions and the role of knowledge on multiple dimensions of ageism. Frequency of interactions with older adults is significantly associated with lower levels of ageism only when the interactions are perceived as favorable. Knowledge of aging is significantly associated with lower levels of ageism. The findings provide valuable information for developing activities to reduce ageism. A new ageism reduction program, which was guided by the study findings and age-friendly university framework, is described. Implications for gerontological education are also discussed.

Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe.

The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 (306VQIVYK311) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aß-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood-brain barrier penetrability and demonstrated a clear selectivity for tau tangles over Aß plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.

Sustainable Asphalt Mixtures with Enhanced Water Resistance for Flood-Prone Regions Using Recycled LDPE and Carnauba-Soybean Oil Additive.

This manuscript presents a comprehensive study on the sustainable optimization of asphalt mixtures tailored for regions prone to flooding. The research addresses the challenges associated with water damage to asphalt pavements by incorporating innovative additives. The study centers on incorporating recycled Low-Density Polyethylene (LDPE) and a tailored Carnauba-Soybean Oil Additive, advancing asphalt mixtures with a Control mix, LDPE (5%) + Control, and LDPE (5%) + 3% Oil + Control. A critical aspect of the research involves subjecting these mixtures to 30 wetting and drying cycles, simulating the conditions prevalent in tropical flood-prone areas. The incorporation of innovative additives in asphalt mixtures has demonstrated significant improvements across various performance parameters. Tensile Strength Ratio (TSR) tests revealed enhanced tensile strength, with the LDPE (5%) + 3% Oil-modified mixture exhibiting an impressive TSR of 85.7%. Dynamic Modulus tests highlighted improved rutting resistance, showcasing a remarkable increase to 214 MPa in the LDPE (5%) with a 3% Oil-modified mixture. The Semi-Circular Bending (SCB) test demonstrated increased fracture resistance and energy absorption, particularly in the LDPE (5%) with 3% Oil-modified mixture. Hamburg Wheel-Tracking (HWT) tests indicated enhanced moisture resistance and superior rutting resistance at 20,000 cycles for the same mixture. Cantabro tests underscored improved aggregate shatter resistance, with the LDPE (5%) + 3% Oil-modified mixture exhibiting the lowest weight loss rate at 9.820%. Field tests provided real-world insights, with the LDPE (5%) + 3% Oil mixture displaying superior stability, a 61% reduction in deflection, and a 256% improvement in surface modulus over the control mixture. This research lays the groundwork for advancing the development of sustainable, high-performance road pavement materials, marking a significant stride towards resilient infrastructure in flood-prone areas.

Advancing Sustainability and Performance with Crushed Bottom Ash as Filler in Polymer-Modified Asphalt Concrete Mixtures.

Amid the growing demand for sustainable pavement solutions and the need to incorporate recycled materials into construction practices, this study explored the viability of using crushed thermal power plant bottom ash as a filler in polymer-modified asphalt concrete mixtures. Conventional lime filler was replaced with bottom ash at varying levels (0%, 25%, 50%, and 75%), and the resulting mixtures were evaluated using several performance tests. The optimal replacement level was determined to be 25%, based on the results of the indirect tensile strength (ITS) test. Comparisons between the control mixture and the 25% bottom ash-modified mixture were conducted using the dynamic modulus test, Cantabro test, Hamburg wheel tracking (HWT) test, and tensile strength ratio (TSR) test. The findings indicate that the 25% bottom ash-modified mixture demonstrated improved performance across multiple parameters. The HWT test showed enhanced rut durability, with a recorded depth of 7.56 mm compared to 8.9 mm for the control mixture. The Cantabro test results revealed lower weight loss percentages for the modified mixture, indicating better abrasion resistance. The dynamic modulus test indicated higher resilience and stiffness in both high- and low-frequency stages. The TSR test highlighted improved moisture resistance, with higher TSR values after 10 wet-drying cycles. These improvements are attributed to the fine particle size and beneficial chemical composition of bottom ash, which enhance the asphalt mixture's density, binder-aggregate adhesion, and overall durability. The results suggest that incorporating 25% crushed bottom ash as a filler in polymer-modified asphalt concrete mixtures is a viable and sustainable approach to improving pavement performance and longevity.

A machine learning-based approach for predicting renal function recovery in general ward patients with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a significant challenge in healthcare. While there are considerable researches dedicated to AKI patients, a crucial factor in their renal function recovery, is often overlooked. Thus, our study aims to address this issue through the development of a machine learning model to predict restoration of kidney function in patients with AKI. METHODS: Our study encompassed data from 350,345 cases, derived from three hospitals. AKI was classified in accordance with the Kidney Disease: Improving Global Outcomes. Criteria for recovery were established as either a 33% decrease in serum creatinine levels at AKI onset, which was initially employed for the diagnosis of AKI. We employed various machine learning models, selecting 43 pertinent features for analysis. RESULTS: Our analysis contained 7,041 and 2,929 patients' data from internal cohort and external cohort respectively. The Categorical Boosting Model demonstrated significant predictive accuracy, as evidenced by an internal area under the receiver operating characteristic (AUROC) of 0.7860, and an external AUROC score of 0.7316, thereby confirming its robustness in predictive performance. SHapley Additive exPlanations (SHAP) values were employed to explain key factors impacting recovery of renal function in AKI patients. CONCLUSION: This study presented a machine learning approach for predicting renal function recovery in patients with AKI. The model performance was assessed across distinct hospital settings, which revealed its efficacy. Although the model exhibited favorable outcomes, the necessity for further enhancements and the incorporation of more diverse datasets is imperative for its application in real- world.

A machine learning approach using conditional normalizing flow to address extreme class imbalance problems in personal health records.

BACKGROUND: Supervised machine learning models have been widely used to predict and get insight into diseases by classifying patients based on personal health records. However, a class imbalance is an obstacle that disrupts the training of the models. In this study, we aimed to address class imbalance with a conditional normalizing flow model, one of the deep-learning-based semi-supervised models for anomaly detection. It is the first introduction of the normalizing flow algorithm for tabular biomedical data. METHODS: We collected personal health records from South Korean citizens (n = 706), featuring genetic data obtained from direct-to-customer service (microarray chip), medical health check-ups, and lifestyle log data. Based on the health check-up data, six chronic diseases were labeled (obesity, diabetes, hypertriglyceridemia, dyslipidemia, liver dysfunction, and hypertension). After preprocessing, supervised classification models and semi-supervised anomaly detection models, including conditional normalizing flow, were evaluated for the classification of diabetes, which had extreme target imbalance (about 2%), based on AUROC and AUPRC. In addition, we evaluated their performance under the assumption of insufficient collection for patients with other chronic diseases by undersampling disease-affected samples. RESULTS: While LightGBM (the best-performing model among supervised classification models) showed AUPRC 0.16 and AUROC 0.82, conditional normalizing flow achieved AUPRC 0.34 and AUROC 0.83 during fifty evaluations of the classification of diabetes, whose base rate was very low, at 0.02. Moreover, conditional normalizing flow performed better than the supervised model under a few disease-affected data numbers for the other five chronic diseases - obesity, hypertriglyceridemia, dyslipidemia, liver dysfunction, and hypertension. For example, while LightGBM performed AUPRC 0.20 and AUROC 0.75, conditional normalizing flow showed AUPRC 0.30 and AUROC 0.74 when predicting obesity, while undersampling disease-affected samples (positive undersampling) lowered the base rate to 0.02. CONCLUSIONS: Our research suggests the utility of conditional normalizing flow, particularly when the available cases are limited, for predicting chronic diseases using personal health records. This approach offers an effective solution to deal with sparse data and extreme class imbalances commonly encountered in the biomedical context.

NASICON-Type Na3V1.5Cr0.4Fe0.1(PO4)3: High-Voltage and High-Rate Cathode Materials for Sodium-Ion Batteries.

Cationic alteration related to a sodium super ion conductor (NASICON)-structured Na3V2(PO4)3 (NVP) is an effective strategy for formulating high-energy and stable cathodes for sodium-ion batteries (SIBs). In this study, we altered the structure of NVP with dual cations, namely, Cr and Fe, to develop Na3V1.5Cr0.4Fe0.1(PO4)3 cathodes for SIBs with high-rate capability (∼71 mAh g-1 at 100 C) and an extreme cycle life output (∼75 mAh g-1 with 95% capacity retention for 10,000 cycles). These excellent electrochemical properties can be ascribed to the synergistic effects of Cr and Fe in the NVP structure, as verified experimentally and theoretically. Therefore, the proposed cosubstitution method can enhance the performance of SIBs by improving their structural stability, electronic conductivity, and phase-change behavior.

Free essential amino acid feeding improves endurance during resistance training via DRP1-dependent mitochondrial remodelling.

BACKGROUND: Loss of muscle strength and endurance with aging or in various conditions negatively affects quality of life. Resistance exercise training (RET) is the most powerful means to improve muscle mass and strength, but it does not generally lead to improvements in endurance capacity. Free essential amino acids (EAAs) act as precursors and stimuli for synthesis of both mitochondrial and myofibrillar proteins that could potentially confer endurance and strength gains. Thus, we hypothesized that daily consumption of a dietary supplement of nine free EAAs with RET improves endurance in addition to the strength gains by RET. METHODS: Male C57BL6J mice (9 weeks old) were assigned to control (CON), EAA, RET (ladder climbing, 3 times a week), or combined treatment of EAA and RET (EAA + RET) groups. Physical functions focusing on strength or endurance were assessed before and after the interventions. Several analyses were performed to gain better insight into the mechanisms by which muscle function was improved. We determined cumulative rates of myofibrillar and mitochondrial protein synthesis using 2H2O labelling and mass spectrometry; assessed ex vivo contractile properties and in vitro mitochondrial function, evaluated neuromuscular junction (NMJ) stability, and assessed implicated molecular singling pathways. Furthermore, whole-body and muscle insulin sensitivity along with glucose metabolism, were evaluated using a hyperinsulinaemic-euglycaemic clamp. RESULTS: EAA + RET increased muscle mass (10%, P < 0.05) and strength (6%, P < 0.05) more than RET alone, due to an enhanced rate of integrated muscle protein synthesis (19%, P < 0.05) with concomitant activation of Akt1/mTORC1 signalling. Muscle quality (muscle strength normalized to mass) was improved by RET (i.e., RET and EAA + RET) compared with sedentary groups (10%, P < 0.05), which was associated with increased AchR cluster size and MuSK activation (P < 0.05). EAA + RET also increased endurance capacity more than RET alone (26%, P < 0.05) by increasing both mitochondrial protein synthesis (53%, P < 0.05) and DRP1 activation (P < 0.05). Maximal respiratory capacity increased (P < 0.05) through activation of the mTORC1-DRP1 signalling axis. These favourable effects were accompanied by an improvement in basal glucose metabolism (i.e., blood glucose concentrations and endogenous glucose production vs. CON, P < 0.05). CONCLUSIONS: Combined treatment with balanced free EAAs and RET may effectively promote endurance capacity as well as muscle strength through increased muscle protein synthesis, improved NMJ stability, and enhanced mitochondrial dynamics via mTORC1-DRP1 axis activation, ultimately leading to improved basal glucose metabolism.

Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.

Inhibitory Regulation of FOXO1 in PPARδ Expression Drives Mitochondrial Dysfunction and Insulin Resistance.

Forkhead box O1 (FOXO1) regulates muscle growth, but the metabolic role of FOXO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FOXO1 in skeletal muscle, we generated skeletal muscle-specific Foxo1 inducible knockout (mFOXO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFOXO1 iKO mice and assessed the correlation between FOXO1 and mitochondria-related protein in the skeletal muscle of patients with diabetes. Obese mFOXO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FOXO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle, and deletion of PPARδ abolished the beneficial effects of FOXO1 deficiency. FOXO1 protein levels were higher in the skeletal muscle of patients with diabetes and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FOXO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FOXO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ.

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Tumor Microenvironment and Genes Affecting the Prognosis of Temozolomide-Treated Glioblastoma.

Glioblastoma (GBM) is the most frequent primary brain tumor in adults and has a poor prognosis due to its resistance to Temozolomide (TMZ). However, there is limited research regarding the tumor microenvironment and genes related to the prognosis of TMZ-treated GBM patients. This study aimed to identify putative transcriptomic biomarkers with predictive value in patients with GBM who were treated with TMZ. Publicly available datasets from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed using CIBERSORTx and Weighted Gene Co-expression Network Analysis (WGCNA) to obtain types of highly expressed cell types and gene clusters. Differentially Expressed Genes analysis was performed and was intersected with the WGCNA results to obtain a candidate gene list. Cox proportional-hazard survival analysis was performed to acquire genes related to the prognosis of TMZ-treated GBM patients. Inflammatory microglial cells, dendritic cells, myeloid cells, and glioma stem cells were highly expressed in GBM tissue, and ACP7, EPPK1, PCDHA8, RHOD, DRC1, ZIC3, and PRLR were significantly associated with survival. While the listed genes have been previously reported to be related to glioblastoma or other types of cancer, ACP7 was identified as a novel gene related to the prognosis of GBM. These findings may have potential implications for developing a diagnostic tool to predict GBM resistance and optimize treatment decisions.

Development of Plug Joint with Polymer-Modified Rubber Asphalt as Filling Material.

Rising traffic volume, heavy loads, and construction activities have raised concerns about expansion joint device damage. This study focuses on developing an innovative expansion joint using polymer-modified rubber asphalt as the filling material to enhance its service life. Styrene-butadiene-styrene (SBS) emerged as a suitable modifier for rubber-modified asphalt, significantly improving elasticity and adhesion. Through the strategic combination of 3- and 2-block linear SBS, the elasticity and adhesion properties were significantly improved, resulting in the formulation of a well-suited polymer-modified rubber asphalt binder. The developed asphalt binder exhibits impressive elastic recovery (61.1% to 66.1%), surpassing commercial products, with enhanced constructability and workability (15% to 21% viscosity reduction). The carefully engineered mastic asphalt mixture showcases self-leveling characteristics at a moderate 210 °C, addressing historical constructability challenges. Settlement is 40% less than traditional hot mix asphalt for surface layers, with improved moisture and stripping resistance, enhancing existing asphalt plug joint durability and workability. Collectively, this novel mixture, comprising polymer-modified rubber and mastic asphalt, showcases the potential to enhance the durability of existing asphalt plug joints while ensuring superior constructability and workability.

Heat Transfer Analysis of Warm Guss Asphalt Concrete for Mini-Trench Overlaying.

Conventional hot mix asphalt overlaying on trench infrastructure typically necessitates extended cooling times for further works and can have adverse effects on buried components, such as electricity cables and hot water pipes. Therefore, this research aims to investigate the use of warm guss mastic asphalt (at an installation temperature of 160 °C) as an overlaying material for mini-trenches, which can reduce the cooling time required for traffic opening and improve the efficiency of the construction process. This research involved two stages: first, lab testing and related research results were used to generate the thermal conductivity and specific heat necessary for simulation work. Second, a finite element model analysis was conducted to evaluate the thermal transmission of the overlaying surface and the buried conduit based on the summer pavement temperature distribution through the Korean Pavement Research Program. Afterward, the field test bed was constructed to verify the simulation. The results indicate that the optimal thickness of the overlaying material and the concrete covering should be designed to ensure thermal durability and meet traffic opening requirements. The overlaying depth of the mini trench using warm mix guss mastic asphalt should be less than 100 mm to meet with the traffic opening time, while the thickness of the concrete covering should be designed to be more than 100 mm to ensure thermal durability. Additionally, the findings suggest that the application of warm guss asphalt could reduce the opening time by 30 min to 1 h and 25 min compared to conventional hot guss asphalt materials. When the pavement surface temperature for the traffic opening is controlled at 50 °C, the asphalt mixture requires at least 2 h to 5 h to meet the cooling criteria for traffic opening, respectively. Overall, this research confirms the potential benefits and optimal use of warm guss mastic asphalt in the construction process of mini-trenches.

Integrative analysis of mitochondrial metabolic reprogramming in early-stage colon and liver cancer.

Gastrointestinal malignancies, including colon adenocarcinoma (COAD) and liver hepatocellular carcinoma (LIHC), remain leading causes of cancer-related deaths worldwide. To better understand the underlying mechanisms of these cancers and identify potential therapeutic targets, we analyzed publicly accessible Cancer Genome Atlas datasets of COAD and LIHC. Our analysis revealed that differentially expressed genes (DEGs) during early tumorigenesis were associated with cell cycle regulation. Additionally, genes related to lipid metabolism were significantly enriched in both COAD and LIHC, suggesting a crucial role for dysregulated lipid metabolism in their development and progression. We also identified a subset of DEGs associated with mitochondrial function and structure, including upregulated genes involved in mitochondrial protein import and respiratory complex assembly. Further, we identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) as a crucial regulator of cancer cell metabolism. Using a genome-scale metabolic model, we demonstrated that HMGCS2 suppression increased glycolysis, lipid biosynthesis, and elongation while decreasing fatty acid oxidation in colon cancer cells. Our study highlights the potential contribution of dysregulated lipid metabolism, including ketogenesis, to COAD and LIHC development and progression and identifies potential therapeutic targets for these malignancies.