Effect of Cl2 Radical on Dry Development of Spin-Coated Metal Oxide Resist.

In this study, the effects of Cl2 radicals on dry development of spin-coated metal oxide resist (MOR) and changes in its surface binding states were investigated to verify the mechanism of dry development. Dry development characteristics of tin hydroxide (Tin OH), which is one of the MOR candidates for next generation lithography, were investigated as functions of process time and temperature using a Cl2 radicals source. Non-UV-exposed Tin OH film showed a linear etch rate (1.77 nm/min) from the initial thickness of ∼50 nm, while the UV-exposed film showed slower etch behavior (1.46 nm/min) in addition to the increase of film thickness for up to 3 min during the Cl2 radical dry development. UV-exposed photoresist (PR) contained more oxygen (Sn-O bonding) in the film due to the removal of butyl compounds from the clusters during the UV exposure process. Therefore, due to the lower reaction of chlorine radicals with Sn-O in the UV-exposed Tin OH than the other bindings, the non-UV-exposed PR was preferentially removed compared to the UV-exposed PR. As the temperature decreases, the overall etch rate decreases, but the difference in etch rate between exposed and unexposed Tin OH becomes larger. Finally, at a substrate temperature of -20 °C, the non-UV-exposed Tin OH with a thickness of 50 nm was completely removed, while ∼30 nm thick PR remained for UV-exposed Tin OH. Eventually, a negative tone development was possible with Cl2 radical plasma due to the difference in activation energy between the UV-exposed and non-UV-exposed films. It is believed that dry development using Cl2 radicals will be one of the most important process techniques for next-generation patterning to remove problems such as pattern leaning, line edge roughness, residue, etc., caused by wet development.

Clean SiO2 atomic layer etching based on physisorption of high boiling point perfluorocarbon.

This study aimed to evaluate the SiO2 atomic layer etching (ALE) process that is selective to Si3N4 based on the physisorption of high boiling point perfluorocarbons (HBP PFCs; C5F8, C7F14, C6F6, and C7F8 have boiling points above room temperature). The lowering of the substrate temperature from 20 °C to -20 °C not only increased SiO2 etch depth per cycle (EPC) but also increased etch selectivity of SiO2/Si3N4 to near infinity. Due to the differences in fluorocarbon adsorption at a temperature during the physisorption depending on boiling points of PFCs, the desorption time and ion bombardment energy during the desorption step needed to be optimized, and higher ion bombardment energy and longer desorption time were required for higher HBP PFCs. Even though near infinity etch selectivity of SiO2/Si3N4 was obtained, for the SiO2 etching masked with Si3N4 patterns, due to the adsorption of PFC on the sidewall of the Si3N4 layer, the difficulty in anisotropic etching could be observed. By adding an O2 descumming step in ALE processes, an anisotropic SiO2 etch profile could be obtained with no adsorption of fluorocarbon on the chamber wall. Therefore, it is believed that the HBP ALE processes can be applicable for achieving high selective SiO2/Si3N4 with more stability and reliability.

Study of CO2 Adsorption Properties on the SrTiO3(001) Surface with Ambient Pressure XPS.

The adsorption properties of CO2 on the SrTiO3(001) surface were investigated using ambient pressure X-ray photoelectron spectroscopy under elevated pressure and temperature conditions. On the Nb-doped TiO2-enriched (1 × 1) SrTiO3 surface, CO2 adsorption, i.e., the formation of CO3 surface species, occurs first at the oxygen lattice site under 10-6 mbar CO2 at room temperature. The interaction of CO2 molecules with oxygen vacancies begins when the CO2 pressure increases to 0.25 mbar. The adsorbed CO3 species on the Nb-doped SrTiO3 surface increases continuously as the pressure increases but starts to leave the surface as the surface temperature increases, which occurs at approximately 373 K on the defect-free surface. On the undoped TiO2-enriched (1 × 1) SrTiO3 surface, CO2 adsorption also occurs first at the lattice oxygen sites. Both the doped and undoped SrTiO3 surfaces exhibit an enhancement of the CO3 species with the presence of oxygen vacancies, thus indicating the important role of oxygen vacancies in CO2 dissociation. When OH species are removed from the undoped SrTiO3 surface, the CO3 species begin to form under 10-6 mbar at 573 K, thus indicating the critical role of OH in preventing CO2 adsorption. The observed CO2 adsorption properties of the various SrTiO3 surfaces provide valuable information for designing SrTiO3-based CO2 catalysts.

Remendable Cross-Linked Alginate/Gelatin Hydrogels Incorporating Nanofibers for Wound Repair and Regeneration.

Wound dressings made from natural-derived polymers are highly valued for their biocompatibility, biodegradability, and biofunctionality. However, natural polymer-based hydrogels can come with their own set of limitations, such as low mechanical strength, limited cell affinity, and the potential cytotoxicity of cross-linkers, which delineate the boundaries of their usage and hamper their practical application. To overcome the limitation of natural-derived polymers, this study utilized a mixture of oxidized alginate and gelatin with 5 mg/mL polycaprolactone (PCL):gelatin nanofiber fragments at a ratio of 7:3 (OGN-7) to develop a hydrogel composite wound dressing that can be injected and has the ability to be remended. The in situ formation of the remendable hydrogel is facilitated by dual cross-linking of oxidized alginate chains with gelatin and PCL/gelatin nanofibers through Schiff-base mechanisms, supported by the physical integration of nanofibers, thereby obviating the need for additional cross-linking agents. Furthermore, OGN-7 exhibits increased stiffness (γ = 79.4-316.3%), reduced gelation time (543 ± 5 to 475 ± 5 s), improved remendability of the hydrogel, and excellent biocompatibility. Notably, OGN-7 achieves full fusion within 1 h of incubation and maintains structural integrity under external stress, effectively overcoming the inherent mechanical weaknesses of natural polymer-based dressings and enhancing biofunctionality. The therapeutic efficacy of OGN-7 was validated through a full-thickness in vivo wound healing analysis, which demonstrated that OGN-7 significantly accelerates wound closure compared to alginate-based dressings and control groups. Histological analysis further revealed that re-epithelialization and collagen deposition were markedly enhanced in the regenerating skin of the OGN-7 group, confirming the superior therapeutic performance of OGN-7. In summary, OGN-7 optimized the synergistic effects of natural polymers, which enhances their collective functionality as a wound dressing and expands their utility across diverse biomedical applications.

Immunoglobulin G4-related disease mimicking an appendiceal neoplasm: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies.

Recent Update on PET/CT Radiotracers for Imaging Cerebral Glioma.

Positron emission tomography/computed tomography (PET/CT) has dramatically altered the landscape of noninvasive glioma evaluation, offering complementary insights to those gained through magnetic resonance imaging (MRI). PET/CT scans enable a multifaceted analysis of glioma biology, supporting clinical applications from grading and differential diagnosis to mapping the full extent of tumors and planning subsequent treatments and evaluations. With a broad array of specialized radiotracers, researchers and clinicians can now probe various biological characteristics of gliomas, such as glucose utilization, cellular proliferation, oxygen deficiency, amino acid trafficking, and reactive astrogliosis. This review aims to provide a recent update on the application of versatile PET/CT radiotracers in glioma research and clinical practice.

Powerful t-tests in the presence of nonclassical measurement error.

This article proposes a powerful alternative to the t-test of the null hypothesis that a coefficient in a linear regression is equal to zero when a regressor is mismeasured. We assume there are two contaminated measurements of the regressor of interest. We allow the two measurement errors to be nonclassical in the sense that they may both be correlated with the true regressor, they may be correlated with each other, and we do not require any location normalizations on the measurement errors. We propose a new maximal t-statistic that is formed from the regression of the outcome onto a maximally weighted linear combination of the two measurements. The critical values of the test are easily computed via a multiplier bootstrap. In simulations, we show that this new test can be significantly more powerful than t-statistics based on OLS or IV estimates. Finally, we apply the proposed test to a study of returns to education based on twin data from the UK. With our maximal t-test, we can discover statistically significant returns to education when standard t-tests do not.

3D in vitro synovial hyperplasia model on polycaprolactone-micropatterned nanofibrous microwells for screening disease-modifying anti-rheumatic drugs.

Rheumatoid arthritis (RA) is known to be caused by autoimmune disorders and can be partially alleviated through Disease-Modifying Antirheumatic Drugs (DMARDs) therapy. However, due to significant variations in the physical environment and condition of each RA patient, the types and doses of DMARDs prescribed can differ greatly. Consequently, there is a need for a platform based on patient-derived cells to determine the effectiveness of specific DMARDs for individual patient. In this study, we established an RA three-dimensional (3D) spheroid that mimics the human body's 3D environment, enabling high-throughput assays by culturing patient-derived synovial cells on a macroscale-patterned polycaprolactone (PCL) scaffold. Fibroblast-like synoviocytes (FLSs) from patient and human umbilical vein endothelial cells (HUVECs) were co-cultured to simulate vascular delivery. Additionally, RA characteristics were identified at both the genetic and cytokine levels using real-time polymerase chain reaction (RT-qPCR) and dot blot assay. The similarities in junctions and adhesion were demonstrated in both actual RA patient tissues and 3D spheroids. The 3D RA spheroid was treated with representative DMARDs, observing changes in reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH) levels, and inflammatory cytokine responses to confirm the varying cell reactions depending on the DMARDs used. This study underscores the significance of the 3D drug screening platform, which can be applied to diverse inflammatory disease treatments as a personalized drug screening system. We anticipate that this platform will become an indispensable tool for advancing and developing personalized DMARD treatment strategies.

A Volumetric Waveguide-Type Rotman Lens Antenna for Three-Dimensional Millimeter-Wave Beamforming.

In this paper, a volumetric Rotman lens antenna operating at 28 GHz is proposed. The design formula and procedure were derived for the 3-D Rotman lens antenna. The number of tilted beams is 3 × 3. The six rectangular blocks are assembled using a metallic bolt. The input port consists of a waveguide, and the output port is made of an open-ended waveguide. The input and output waveguides are drilled in a flat conducting plate. The input and output port positions are optimized. Simulated and measured results show that the radiating beam is controlled almost exactly as calculated. Compared with the previous two-stage stacked Rotman lens antenna, the proposed Rotman lens antenna can dramatically decrease the antenna volume by approximately 75%.

Context-dependent genomic locus effects on antibody production in recombinant Chinese hamster ovary cells generated through random integration.

High-yield production of therapeutic protein using Chinese hamster ovary (CHO) cells requires stable cell line development (CLD). CLD typically uses random integration of transgenes; however, this results in clonal variation and subsequent laborious clone screening. Therefore, site-specific integration of a protein expression cassette into a desired chromosomal locus showing high transcriptional activity and stability, referred to as a hot spot, is emerging. Although positional effects are important for therapeutic protein expression, the sequence-specific mechanisms by which hotspots work are not well understood. In this study, we performed whole-genome sequencing (WGS) to locate randomly inserted vectors in the genome of recombinant CHO cells expressing high levels of monoclonal antibodies (mAbs) and experimentally validated these locations and vector compositions. The integration site was characterized by active histone marks and potential enhancer activities, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mediated indel mutations in the region upstream of the integration site led to a significant reduction in specific antibody productivity by up to 30%. Notably, the integration site and its core region did not function equivalently outside the native genomic context, showing a minimal effect on the increase in exogenous protein expression in the host cell line. We also observed a superior production capacity of the mAb expressing cell line compared to that of the host cell line. Collectively, this study demonstrates that developing recombinant CHO cell lines to produce therapeutic proteins at high levels requires a balance of factors including transgene configuration, genomic locus landscape, and host cell properties.

An electroencephalogram microdisplay to visualize neuronal activity on the brain surface.

Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.

Position-Sensing Graph Neural Networks: Proactively Learning Nodes Relative Positions.

Most existing graph neural networks (GNNs) learn node embeddings using the framework of message passing and aggregation. Such GNNs are incapable of learning relative positions between graph nodes within a graph. To empower GNNs with the awareness of node positions, some nodes are set as anchors. Then, using the distances from a node to the anchors, GNNs can infer relative positions between nodes. However, position-aware GNNs (P-GNNs) arbitrarily select anchors, leading to compromising position awareness and feature extraction. To eliminate this compromise, we demonstrate that selecting evenly distributed and asymmetric anchors is essential. On the other hand, we show that choosing anchors that can aggregate embeddings of all the nodes within a graph is NP-complete. Therefore, devising efficient optimal algorithms in a deterministic approach is practically not feasible. To ensure position awareness and bypass NP-completeness, we propose position-sensing GNNs (PSGNNs), learning how to choose anchors in a backpropagatable fashion. Experiments verify the effectiveness of PSGNNs against state-of-the-art GNNs, substantially improving performance on various synthetic and real-world graph datasets while enjoying stable scalability. Specifically, PSGNNs on average boost area under the curve (AUC) more than 14% for pairwise node classification and 18% for link prediction over the existing state-of-the-art position-aware methods. Our source code is publicly available at: https://github.com/ZhenyueQin/PSGNN.

The effect of opioid use on traffic fatalities.

We use a difference-in-differences design to study the effect of opioid use on traffic fatalities. Following Alpert et al., we focus on the 1996 introduction and marketing of OxyContin, and we examine its long-term impacts on traffic fatalities involving Schedule II drugs or heroin. Based on the national fatal vehicle crash database, we find that the states heavily targeted by the initial marketing of OxyContin (i.e., non-triplicate states) experienced 2.4 times more traffic fatalities (1.6 additional deaths per million individuals) involving Schedule II drugs or heroin during 2011-2019, when overdose deaths from heroin and fentanyl became more prominent. We find no difference in traffic fatalities until after the mid-2000s between states with and without a triplicate prescription program. The effect is mainly concentrated in fatal crashes with drug involvement of drivers ages between 25 and 44. Our results highlight additional long-term detrimental consequences of the introduction and marketing of OxyContin.

Synergistic Effect of Ferroptosis-Inducing Nanoparticles and X-Ray Irradiation Combination Therapy.

Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron-dependent manner. Radiation therapy, a common treatment method, has limitations as a stand-alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis-inducing drugs help alleviate radiation resistance, there are no safe ferroptosis-inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid-based nanoparticles (FHA-NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA-NPs and apoptosis by X-ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X-rays with the iron-oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X-ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.

Combination of [18F]FDG and [18F]PSMA-1007 PET/CT predicts tumour aggressiveness at staging and biochemical failure postoperatively in patients with prostate cancer.

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.

Discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for treating cancers with microsatellite instability.

Microsatellite instability (MSI) is a hypermutable condition caused by DNA mismatch repair system defects, contributing to the development of various cancer types. Recent research has identified Werner syndrome ATP-dependent helicase (WRN) as a promising synthetic lethal target for MSI cancers. Herein, we report the first discovery of thiophen-2-ylmethylene bis-dimedone derivatives as novel WRN inhibitors for MSI cancer therapy. Initial computational analysis and biological evaluation identified a new scaffold for a WRN inhibitor. Subsequent SAR study led to the discovery of a highly potent WRN inhibitor. Furthermore, we demonstrated that the optimal compound induced DNA damage and apoptotic cell death in MSI cancer cells by inhibiting WRN. This study provides a new pharmacophore for WRN inhibitors, emphasizing their therapeutic potential for MSI cancers.

Knockout of the lysosomal membrane protein, LAMP2C, improves transient gene expression in HEK293 cells via increased intracellular plasmid availability.

Plasmid-based transfection can be used in many applications such as transient gene expression (TGE)-based therapeutic protein production. These applications preferentially require maximization of intracellular plasmid availability. Here, we applied a lysosome engineering approach to alleviate lysosome-mediated nucleic acid degradation and enhance the TGE in mammalian cells. By knocking out the lysosomal membrane protein LAMP2C, which is known to be the main player in RNautophagy/DNautophagy (RDA), we significantly improved transient fluorescent protein expression in HEK293 cells by improving the retention rate of transfected plasmids; however, this effect was not observed in CHO cells. Additional knockout of a lysosomal membrane transporter and another RDA player, SIDT2, was ineffective, regardless of the presence of LAMP2C. LAMP2C knockout enhanced TGE-based mAb production in HEK293 cells by up to 2.82-fold increase in specific mAb productivity. Taken together, these results demonstrate that HEK293 cells can be engineered to improve the usage of the transfected plasmid via knockout of the lysosomal membrane protein LAMP2C and provide efficient host cells in TGE systems for therapeutic protein production.

11 C-Acetate PET/CT for Reactive Astrogliosis Outperforms 11 C-Methionine PET/CT in Glioma Classification and Survival Prediction.

PURPOSE: 11 C-acetate (ACE) PET/CT visualizes reactive astrogliosis in tumor microenvironment. This study compared 11 C-ACE and 11 C-methionine (MET) PET/CT for glioma classification and predicting patient survival. PATIENTS AND METHODS: In this prospective study, a total of 142 patients with cerebral gliomas underwent preoperative MRI, 11 C-MET PET/CT, and 11 C-ACE PET/CT. Tumor-to-contralateral cortex (TNR MET ) and tumor-to-choroid plexus ratios (TNR ACE ) were calculated for 11 C-MET and 11 C-ACE. The Kruskal-Wallis test and Bonferroni post hoc analysis were used to compare the differences in 11 C-TNR MET and 11 C-TNR ACE . The Cox proportional hazards regression analysis and classification and regression tree models were used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: The median 11 C-TNR MET and 11 C-TNR ACE for oligodendrogliomas (ODs), IDH1 -mutant astrocytomas, IDH1 -wildtype astrocytomas, and glioblastomas were 2.75, 1.40, 2.30, and 3.70, respectively, and 1.40, 1.20, 1.77, and 2.87, respectively. The median 11 C-TNR MET was significantly different among the groups, except between ODs and IDH1 -wildtype astrocytomas, whereas the median 11 C-TNR ACE was significantly different among all groups. The classification and regression tree model identified 4 risk groups ( IDH1 -mutant with 11 C-TNR ACE ≤ 1.4, IDH1 -mutant with 11 C-TNR ACE > 1.4, IDH1 -wildtype with 11 C-TNR ACE ≤ 1.8, and IDH1 -wildtype with 11 C-TNR ACE > 1.8), with median PFS of 52.7, 44.5, 25.9, and 8.9 months, respectively. Using a 11 C-TNR ACE cutoff of 1.4 for IDH1 -mutant gliomas and a 11 C-TNR ACE cutoff of 2.0 for IDH1 -wildtype gliomas, all gliomas were divided into 4 groups with median OS of 52.7, 46.8, 27.6, and 12.0 months, respectively. Significant differences in PFS and OS were observed among the 4 groups after correcting for multiple comparisons. CONCLUSIONS: 11 C-ACE PET/CT is better for glioma classification and survival prediction than 11 C-MET PET/CT, highlighting its potential role in cerebral glioma patients.

Cyclohexylalanine-Containing α-Helical Amphipathic Peptide Targets Cardiolipin, Rescuing Mitochondrial Dysfunction in Kidney Injury.

Mitochondrial dysfunction is linked to degenerative diseases, resulting from cardiolipin (CL)-induced disruption of cristae structure in the inner mitochondrial membrane (IMM); therefore, preserving cristae and preventing CL remodeling offer effective strategies to maintain mitochondrial function. To identify reactive oxygen species (ROS)-blocking agents against mitochondrial dysfunction, a library of cyclohexylamine-containing cell-penetrating α-helical amphipathic "bundle" peptides were screened. Among these, CMP3013 is selectively bound to abnormal mitochondria, preserving the cristae structure impaired by mitochondria-damaging agents. With a stronger affinity for CL compared with other IMM lipid components, CMP3013 exhibited high selectivity. Consequently, it protected cristae, reduced ROS production, and enhanced adenosine triphosphate (ATP) generation. In mouse models of acute kidney injury, a 1 mg/kg dose of CMP3013 demonstrated remarkable efficacy, highlighting its potential as a therapeutic agent for mitochondrial dysfunction-related disorders. Overall, CMP3013 represents a promising agent for mitigating mitochondrial dysfunction and associated diseases.

Visualizing Cancer-Originating Acetate Uptake Through MCT1 in Reactive Astrocytes in the Glioblastoma Tumor Microenvironment.

BACKGROUND: Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explores 11C-acetate PET as an imaging technique for detecting reactive astrogliosis. METHODS: Through in vitro, mouse models, and human tissue experiments, we examined the association between elevated 11C-acetate uptake and reactive astrogliosis in gliomas. We explored acetate from glioblastoma cells, which triggers reactive astrogliosis in neighboring astrocytes by upregulating MAO-B and MCT1 expression. We evaluated the presence of cancer stem cells in the reactive astrogliosis region of glioblastomas and assessed the correlation between the volume of 11C-acetate uptake beyond MRI and prognosis. RESULTS: Elevated 11C-acetate uptake is associated with reactive astrogliosis and astrocytic MCT1 in the periphery of glioblastomas in human tissues and mouse models. Glioblastoma cells exhibit increased acetate production as a result of glucose metabolism, with subsequent secretion of acetate. Acetate derived from glioblastoma cells induces reactive astrogliosis in neighboring astrocytes by increasing the expression of MAO-B and MCT1. We found cancer stem cells within the reactive astrogliosis at the tumor periphery. Consequently, a larger volume of 11C-acetate uptake beyond contrast-enhanced MRI was associated with worse prognosis. CONCLUSION: Our results highlight the role of acetate derived from glioblastoma cells in inducing reactive astrogliosis and underscore the potential value of 11C-acetate PET as an imaging technique for detecting reactive astrogliosis, offering important implications for the diagnosis and treatment of glioblastomas.