Standardized multi-institutional data analysis of fixed and removable prosthesis: estimation of life expectancy with regards to variable risk factors.

PURPOSE: This study aims to assess and predict lifespan of dental prostheses using newly developed Korean Association of Prosthodontics (KAP) criteria through a large-scale, multi-institutional survey. MATERIALS AND METHODS: Survey was conducted including 16 institutions. Cox proportional hazards model and principal component analysis (PCA) were used to find out relevant factors and predict life expectancy. RESULTS: 1,703 fixed and 815 removable prostheses data were collected and evaluated. Statistically significant factors in fixed prosthesis failure were plaque index and material type, with a median survival of 10 to 18 years and 14 to 20 years each. In removable prosthesis, factors were national health insurance coverage, antagonist type, and prosthesis type (complete or partial denture), with median survival of 10 to 13 years, 11 to 14 years, and 10 to 15 years each. For still-usable prostheses, PCA analysis predicted an additional 3 years in fixed and 4.8 years in removable prosthesis. CONCLUSION: Life expectancy of a prosthesis differed significantly by factors mostly controllable either by dentist or a patient. Overall life expectancy was shown to be longer than previous research.

The complete mitochondrial genome of the ice krill Euphausia crystallorophias Holt & Tattersall, 1906 (Euphausiacea, Euphausiidae), from the Ross Sea, Antarctica.

The mitogenome of Euphausia crystallorophias collected from the Ross Sea Region Marine Protected Area (RSR MPA) is described for the first time. The assembled mitogenome was 17,291 bp in length and consisted of two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and noncoding regions, all of which were identical to those of other euphausiid species. The most common start codon for the 13 PCGs was ATG, and the most common termination codon was TAA. The overall G + C content was 33.2% in the heavy strand. Euphausia crystallorophias was sister to E. superba in the phylogenetic analysis. The mitogenome of E. crystallorophias provided significant DNA molecular data for further identification and phylogenetic analysis within the euphausiids.

Dietary effects of protected fat, glycerol, and soybean meal on performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions.

Objective: This study aimed to determine the effects of increasing energy and protein levels in diets by including protected fat (PF), glycerol (GL), and soybean meal (SBM) on growth performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions. Methods: Thirty-six steers (initial BW, 724.9 ± 58.3 kg; age, 25.5 ± 0.4 month) were assigned into Control (TDN 76%, CP 15%), PF (TDN 83.6%, CP 15%), PF+GL (TDN 83.6%, CP 15%) and PF+GL+SBM (TDN 83.6%, CP 16.5%) by randomized complete block design for a total of 16 weeks with division of 4 week periods. The average temperature-humidity index was 87.0 (1st period; Severe), 82.8 (2nd; Moderate), 71.4 (3rd; Comfort), and 68.1 (4th; Comfort). Results: The DMI showed no treatments differences during the whole experiment. However, DMI in 1st and 2nd period decreased by approximately 30% and 10% compared to 4th period, respectively. Higher ADG and FCR were noted for treatments compared to Control at both 1st and 2nd period (p<0.05). There were no treatment effects on rectal temperature (RT), cortisol, and behaviors during the entire experiment. However, both RT and cortisol in 0, 1st and 2nd period were higher than those of 3rd and 4th period (p<0.05). Carcass yield and grade remained unaffected by increasing TDN and CP levels. Behavioral changes in the hot season (1st period) included reduced lying (43%), increased standing (48%), decreased walking (62%), and decreased eating (38%) (p<0.05), with an increase in drinking by 54%. Rumination during standing was 53% higher, while rumination during lying was about 33% lower compared to the post-hot season (3rd period) (p<0.05). Conclusion: Dietary supplementation of protected fat in late-fattening Hanwoo steers under heat stress had a positive effect on preventing a reduction in performance.

Multi-level, forming and filament free, bulk switching trilayer RRAM for neuromorphic computing at the edge.

CMOS-RRAM integration holds great promise for low energy and high throughput neuromorphic computing. However, most RRAM technologies relying on filamentary switching suffer from variations and noise, leading to computational accuracy loss, increased energy consumption, and overhead by expensive program and verify schemes. We developed a filament-free, bulk switching RRAM technology to address these challenges. We systematically engineered a trilayer metal-oxide stack and investigated the switching characteristics of RRAM with varying thicknesses and oxygen vacancy distributions to achieve reliable bulk switching without any filament formation. We demonstrated bulk switching at megaohm regime with high current nonlinearity, up to 100 levels without compliance current. We developed a neuromorphic compute-in-memory platform and showcased edge computing by implementing a spiking neural network for an autonomous navigation/racing task. Our work addresses challenges posed by existing RRAM technologies and paves the way for neuromorphic computing at the edge under strict size, weight, and power constraints.

Surgical Strategy for Petroclival Meningioma-Related Trigeminal Neuralgia: The Role of Porus Trigeminus Opening.

OBJECTIVE: Petroclival meningiomas invade Meckel's cave through the porus trigeminus, leading to secondary trigeminal neuralgia. Microsurgery and stereotactic radiosurgery (SRS) are the typical treatment options. This study investigated symptom control, outcomes, and surgical strategies for PC meningioma-induced TN. METHODS: We retrospectively analyzed 28 TN patients with PC meningiomas who underwent microsurgical nerve decompression between January 2021 and February 2023. In all patients undergoing a transpetrosal approach, the porus trigeminus was opened to enable the removal of the entire tumor within Meckel's cave. Clinical outcomes were assessed using the Barrow Neurologic Institute (BNI) pain intensity scale. Risk factors for poor TN outcomes and poor facial numbness were analyzed. RESULTS: Among 28 patients, 21 (75%) underwent the transpetrosal approach, 5 (17.9%) underwent the retrosigmoid approach, and 2 (7.1%) underwent the Dolenc approach. Following microsurgery, 23 patients (82.1%) experienced TN relief without further medication (BNI I or II). TN recurrence occurred in 2 patients (7.1%), and 3 patients (10.7%) did not achieve TN relief. Cavernous sinus invasion was significantly correlated with poor TN outcomes (P = 0.047). A history of previous SRS (P = 0.011) and upper clivus type tumor (P = 0.018) were significantly associated with poor facial numbness. CONCLUSIONS: Microsurgical nerve decompression is effective in improving BNI scores in patients with TN associated with PC meningiomas. Considering the results of our study, the opening of the porus trigeminus can be considered as a suggested procedure in the treatment of PC meningiomas, especially in cases accompanied by TN.

Interspecific Variations in the Internal Mercury Isotope Dynamics of Antarctic Penguins: Implications for Biomonitoring.

Mercury (Hg) biomonitoring requires a precise understanding of the internal processes contributing to disparities between the Hg sources in the environment and the Hg measured in the biota. In this study, we investigated the use of Hg stable isotopes to trace Hg accumulation in Adélie and emperor penguin chicks from four breeding colonies in Antarctica. Interspecific variation of Δ199Hg in penguin chicks reflects the distinct foraging habitats and Hg exposures in adults. Chicks at breeding sites where adult penguins predominantly consumed mesopelagic prey showed relatively lower Δ199Hg values than chicks that were primarily fed epipelagic krill. Substantial δ202Hg variations in chick tissues were observed in both species (Adélie: -0.11 to 1.13‰, emperor: -0.27 to 1.15‰), whereas only emperor penguins exhibited the lowest δ202Hg in the liver and the highest in the feathers. Our results indicate that tissue-specific δ202Hg variations and their positive correlations with % MeHg resulted from MeHg demethylation in the liver and kidneys of emperor penguin chicks, whereas Adélie penguin chicks showed different internal responses depending on their exposure to dietary MeHg. This study highlights the importance of considering intra- and interspecific variations in adult foraging ecology and MeHg demethylation when selecting penguin chicks for Hg biomonitoring.

Reverse fabrication method of thin-film composite membranes for hydrogen separation.

A reverse method involves the pre-formation of an Matrimid (MI)-selective layer, followed by a porous polysulfone (PSF) support deposition. The membrane exhibited a high H2/CH4 selectivity and a moderate H2 permeance. This study introduces a facile method to produce membranes with inexpensive materials.

Exploring prognostic factors and treatment strategies for long-term survival in pleomorphic xanthoastrocytoma patients.

Pleomorphic xanthoastrocytomas (PXA) are rare, accounting for < 1% of all astrocytomas. Literature on the clinical course and treatment outcomes of PXAs is limited. The study aimed to determine prognosis and treatment strategies for PXAs. Patients who had PXAs surgery between 2000-2021 were retrospectively analyzed for demographics and radiological characteristics. Initial and salvage treatment outcomes were recorded. Overall, 40 and 9 patients had grade 2 and 3 PXAs; their 5-year progression-free survival (PFS) rates were 75.8% and 37.0%, respectively (p = 0.003). Univariate analysis revealed that strong T1 enhancement (p = 0.036), infiltrative tumor margins (p < 0.001), peritumoral edema (p = 0.003), WHO grade (p = 0.005), and gross total resection (p = 0.005) affected the PFS. Multivariate analysis revealed that the WHO grade (p = 0.010) and infiltrative tumor margins (p = 0.008) influenced the PFS. The WHO grade (p = 0.027) and infiltrative tumor margins (p = 0.027) also affected the overall survival (OS). Subgroup analysis for grade 2 PXAs revealed no significant associations between adjuvant radiation therapy and the PFS and OS. This study highlighted the heterogeneous nature of PXAs and its impact on patient prognosis. Infiltrative tumor margins emerged as a key prognostic factor. Our findings have emphasized the prognostic relevance of radiological features and the need for larger studies on comprehensive management.

High-density transparent graphene arrays for predicting cellular calcium activity at depth from surface potential recordings.

Optically transparent neural microelectrodes have facilitated simultaneous electrophysiological recordings from the brain surface with the optical imaging and stimulation of neural activity. A remaining challenge is to scale down the electrode dimensions to the single-cell size and increase the density to record neural activity with high spatial resolution across large areas to capture nonlinear neural dynamics. Here we developed transparent graphene microelectrodes with ultrasmall openings and a large, transparent recording area without any gold extensions in the field of view with high-density microelectrode arrays up to 256 channels. We used platinum nanoparticles to overcome the quantum capacitance limit of graphene and to scale down the microelectrode diameter to 20 µm. An interlayer-doped double-layer graphene was introduced to prevent open-circuit failures. We conducted multimodal experiments, combining the recordings of cortical potentials of microelectrode arrays with two-photon calcium imaging of the mouse visual cortex. Our results revealed that visually evoked responses are spatially localized for high-frequency bands, particularly for the multiunit activity band. The multiunit activity power was found to be correlated with cellular calcium activity. Leveraging this, we employed dimensionality reduction techniques and neural networks to demonstrate that single-cell and average calcium activities can be decoded from surface potentials recorded by high-density transparent graphene arrays.

Production of Mono-Hydroxylated Derivatives of Terpinen-4-ol by Bacterial CYP102A1 Enzymes.

CYP102A1 from Bacillus megaterium is an important enzyme in biotechnology, because engineered CYP102A1 enzymes can react with diverse substrates and produce human cytochrome P450-like metabolites. Therefore, CYP102A1 can be applied to drug metabolite production. Terpinen-4-ol is a cyclic monoterpene and the primary component of essential tea tree oil. Terpinen-4-ol was known for therapeutic effects, including antibacterial, antifungal, antiviral, and anti-inflammatory. Because terpenes are natural compounds, examining novel terpenes and investigating the therapeutic effects of terpenes represent responses to social demands for eco-friendly compounds. In this study, we investigated the catalytic activity of engineered CYP102A1 on terpinen-4-ol. Among CYP102A1 mutants tested here, the R47L/F81I/F87V/E143G/L188Q/N213S/E267V mutant showed the highest activity to terpinen-4-ol. Two major metabolites of terpinen-4-ol were generated by engineered CYP102A1. Characterization of major metabolites was confirmed by liquid chromatography-mass spectrometry (LC-MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopy (NMR). Based on the LC-MS results, the difference in mass-to-charge ratio of an ion (m/z) between terpinen-4-ol and its major metabolites was 16. One major metabolite was defined as 1,4-dihydroxy-p-menth-2-ene by NMR. Given these results, we speculate that another major metabolite is also a mono-hydroxylated product. Taken together, we suggest that CYP102A1 can be applied to make novel terpene derivatives.

Chromosome-level genome assembly and annotation of the Antarctica whitefin plunderfish Pogonophryne albipinna.

The Antarctic whitefin plunderfish Pogonophryne albipinna belongs to the family Artedidraconidae, a key component of Antarctic benthic ecosystems within the order Perciformes and the suborder Notothenioidei. While genome research on P. albipinna using short-read sequencing is available, high-quality genome assembly and annotation employing long-read sequencing have yet to be performed. This study presents a chromosome-scale genome assembly and annotation for P. albipinna, utilizing a combination of Illumina short-read, PacBio long-read, and Hi-C sequencing technologies. The resulting genome assembly spans approximately 1.07 Gb, with a longest scaffold measuring 59.39 Mb and an N50 length of 41.76 Mb. Of the 1,111 Hi-C scaffolds, 23 exceeded 10 Mb and were thus classified as chromosome-level. BUSCO completeness was assessed at 95.6%. The assembled genome comprises 50.68% repeat sequences, and a total of 31,128 protein-coding genes were predicted. This study will enhance our understanding of the genomic characteristics of cryonotothenioids and facilitate comparative analyses of their adaptation and evolution in extreme environments.

Prediction of pseudoprogression in post-treatment glioblastoma using dynamic susceptibility contrast-derived oxygenation and microvascular transit time heterogeneity measures.

OBJECTIVES: To evaluate the added value of MR dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI)-derived tumour microvascular and oxygenation information with cerebral blood volume (CBV) to distinguish pseudoprogression from true progression (TP) in post-treatment glioblastoma. METHODS: This retrospective single-institution study included patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and a newly developed or enlarging measurable contrast-enhancing mass within 12 weeks after concurrent chemoradiotherapy. CBV, capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were obtained from DSC-PWI. Predictors were selected using univariable logistic regression, and performance was measured with adjusted diagnostic odds with tumour volume and area under the curve (AUC) of receiver operating characteristics analysis. RESULTS: A total of 103 patients were included (mean age, 59.6 years; 59 women), with 67 cases of TP and 36 cases of pseudoprogression. Pseudoprogression exhibited higher CTH (4.0 vs. 3.4, p = .019) and higher OEF (12.7 vs. 10.7, p = .014) than TP, but a similar CBV (1.48 vs. 1.53, p = .13) and CMRO2 (7.7 vs. 7.3s, p = .598). Independent of tumour volume, both high CTH (adjusted odds ratio [OR] 1.52; 95% confidence interval [CI]: 1.11-2.09, p = .009) and high OEF (adjusted OR 1.17; 95% CI:1.03-1.33, p = .016) were predictors of pseudoprogression. The combination of CTH, OEF, and CBV yielded higher diagnostic performance (AUC 0.71) than CBV alone (AUC 0.65). CONCLUSION: High intratumoural capillary transit heterogeneity and high oxygen extraction fraction derived from DSC-PWI have enhanced the diagnostic value of CBV in pseudoprogression of post-treatment IDH-wild type glioblastoma. CLINICAL RELEVANCE STATEMENT: In the early post-treatment stage of glioblastoma, pseudoprogression exhibited both high oxygen extraction fraction and high capillary transit heterogeneity and these dynamic susceptibility contrast-perfusion weighted imaging derived parameters have added value in cerebral blood volume-based noninvasive differentiation of pseudoprogression from true progression. KEY POINTS: • Capillary transit time heterogeneity and oxygen extraction fraction can be measured noninvasively through processing of dynamic susceptibility contrast imaging. • Pseudoprogression exhibited higher capillary transit time heterogeneity and higher oxygen extraction fraction than true progression. • A combination of cerebral blood volume, capillary transit time heterogeneity, and oxygen extraction fraction yielded the highest diagnostic performance (area under the curve 0.71).

Hypoxia stabilizes SETDB1 to maintain genome stability.

Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element-derived double-stranded RNAs, thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.

Design of hypoxia responsive CRISPR-Cas9 for target gene regulation.

The CRISPR-Cas9 system is a widely used gene-editing tool, offering unprecedented opportunities for treating various diseases. Controlling Cas9/dCas9 activity at specific location and time to avoid undesirable effects is very important. Here, we report a conditionally active CRISPR-Cas9 system that regulates target gene expression upon sensing cellular environmental change. We conjugated the oxygen-sensing transcription activation domain (TAD) of hypoxia-inducing factor (HIF-1α) with the Cas9/dCas9 protein. The Cas9-TAD conjugate significantly increased endogenous target gene cleavage under hypoxic conditions compared with that under normoxic conditions, whereas the dCas9-TAD conjugate upregulated endogenous gene transcription. Furthermore, the conjugate system effectively downregulated the expression of SNAIL, an essential gene in cancer metastasis, and upregulated the expression of the tumour-related genes HNF4 and NEUROD1 under hypoxic conditions. Since hypoxia is closely associated with cancer, the hypoxia-dependent Cas9/dCas9 system is a novel addition to the molecular tool kit that functions in response to cellular signals and has potential application for gene therapeutics.

Production of an O-desmethylated product, a major human metabolite, of rabeprazole sulfide by bacterial P450 enzymes.

Rabeprazole is a common type of proton pump inhibitor (PPI) used to treat various peptic disorders. Unlike most PPI drugs, rabeprazole is spontaneously reduced to rabeprazole sulfide (thioether) when it is given to patients. As a result, rabeprazole sulfide is considered one of the active metabolites of rabeprazole. Rabeprazole sulfide is mainly metabolized to desmethyl rabeprazole sulfide by CYP2C19 and CYP2D6 in people. However, the pharmacological efficacy and safety of desmethyl rabeprazole sulfide have not yet been investigated. Its usage is challenging due to the high cost associated with the drug. In this study, we found CYP102A1 mutants that can produce desmethyl rabeprazole sulfide as a major metabolite of rabeprazole sulfide. The chemical characteristics of the major product were confirmed using high-performance liquid chromatography, LC-mass spectrometry, and nuclear magnetic resonance spectroscopy. CYP102A1 mutants R47L/F87V/L188Q, R47L/F87V/L188Q/A335V/Q359R, and R47L/F87V/L188Q/I254V/D351E showed kcat values of 39, 93, and 88 min-1, respectively, for O-desmethylation of rabeprazole sulfide. Furthermore, the highest concentration of desmethyl rabeprazole sulfide product from 2 mM rabeprazole sulfide at optimal conditions was obtained in bacterial whole-cell biotransformation with the R47L/F87V/L188Q mutant, reaching 0.63 mM at 4-h incubation. In conclusion, we present a platform that facilitates the efficient and sustainable production of the desmethylated product from rabeprazole sulfide for use in the biopharmaceutical industry.

A chromosome-level reference genome of the Antarctic blackfin icefish Chaenocephalus aceratus.

The blackfin Icefish (Chaenocephalus aceratus) belongs to the family Channichthyidae and the suborder Notothenioidei which lives in the Antarctic. We corrected the mis-scaffolds in the previous linkage map results by Hi-C analysis to obtain improved results for chromosome-level genome assembly. The final assembly analysis resulted in a total of 3,135 scaffolds, a genome size of 1,065.72 Mb, and an N50 of 33.46 Mb. 820.24 Mb, representing 88.88% of the total genome, is anchored to 24 chromosomes. The final gene set of 38,024 genes, including AFGPs, was annotated using RNA evidence, proteins, and ab-initio predictions. The complete percentage of BUSCO analysis is 92.7%. In this study, we aim to contribute to the study of polar fishes by improving the genome sequences of the blackfin icefish with the AFGP genes belonging to the Notothenoidei.

Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.

Cell cycle and apoptosis regulator 2 (CCAR2), also known as deleted in breast cancer 1 (DBC1), has been recently identified as a master regulator of transcriptional processes and plays diverse roles in physiology and pathophysiology, including as a regulator of apoptosis, DNA repair, metabolism, and tumorigenesis. CCAR2 functions as a coregulator of various transcription factors and a critical regulator of numerous epigenetic modifiers. Based on its ability to stimulate apoptosis by activating and stabilizing p53, CCAR2 was initially considered to be a tumor suppressor. However, an increasing number of studies have shown that CCAR2 also functions as a tumor-promoting coregulator by activating oncogenic transcription factors and regulating the enzymatic activity of epigenetic modifiers, indicating that CCAR2 may play a dual role in cancer progression by acting as a tumor suppressor and tumor promoter. Here, we review recent progress in understanding the dual tumor-suppressing and oncogenic roles of CCAR2 in cancer. We discuss CCAR2 domain structures, its interaction partners, and the molecular mechanisms by which it regulates the activities of transcription factors and epigenetic modifiers.

Imaging-Based Versus Pathologic Survival Stratifications of Diffuse Glioma According to the 2021 WHO Classification System.

OBJECTIVE: Imaging-based survival stratification of patients with gliomas is important for their management, and the 2021 WHO classification system must be clinically tested. The aim of this study was to compare integrative imaging- and pathology-based methods for survival stratification of patients with diffuse glioma. MATERIALS AND METHODS: This study included diffuse glioma cases from The Cancer Genome Atlas (training set: 141 patients) and Asan Medical Center (validation set: 131 patients). Two neuroradiologists analyzed presurgical CT and MRI to assign gliomas to five imaging-based risk subgroups (1 to 5) according to well-known imaging phenotypes (e.g., T2/FLAIR mismatch) and recategorized them into three imaging-based risk groups, according to the 2021 WHO classification: group 1 (corresponding to risk subgroup 1, indicating oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, and 1p19q-co-deleted), group 2 (risk subgroups 2 and 3, indicating astrocytoma, IDH-mutant), and group 3 (risk subgroups 4 and 5, indicating glioblastoma, IDHwt). The progression-free survival (PFS) and overall survival (OS) were estimated for each imaging risk group, subgroup, and pathological diagnosis. Time-dependent area-under-the receiver operating characteristic analysis (AUC) was used to compare the performance between imaging-based and pathology-based survival model. RESULTS: Both OS and PFS were stratified according to the five imaging-based risk subgroups (P < 0.001) and three imaging-based risk groups (P < 0.001). The three imaging-based groups showed high performance in predicting PFS at one-year (AUC, 0.787) and five-years (AUC, 0.823), which was similar to that of the pathology-based prediction of PFS (AUC of 0.785 and 0.837). Combined with clinical predictors, the performance of the imaging-based survival model for 1- and 3-year PFS (AUC 0.813 and 0.921) was similar to that of the pathology-based survival model (AUC 0.839 and 0.889). CONCLUSION: Imaging-based survival stratification according to the 2021 WHO classification demonstrated a performance similar to that of pathology-based survival stratification, especially in predicting PFS.

Aquaporin-4 Deficiency is Associated with Cognitive Impairment and Alterations in astrocyte-neuron Lactate Shuttle.

Cognitive impairment refers to notable declines in cognitive abilities including memory, language, and emotional stability leading to the inability to accomplish essential activities of daily living. Astrocytes play an important role in cognitive function, and homeostasis of the astrocyte-neuron lactate shuttle (ANLS) system is essential for maintaining cognitive functions. Aquaporin-4 (AQP-4) is a water channel expressed in astrocytes and has been shown to be associated with various brain disorders, but the direct relationship between learning, memory, and AQP-4 is unclear. We examined the relationship between AQP-4 and cognitive functions related to learning and memory. Mice with genetic deletion of AQP-4 showed significant behavioral and emotional changes including hyperactivity and instability, and impaired cognitive functions such as spatial learning and memory retention. 18 F-FDG PET imaging showed significant metabolic changes in the brains of AQP-4 knockout mice such as reductions in glucose absorption. Such metabolic changes in the brain seemed to be the direct results of changes in the expression of metabolite transporters, as the mRNA levels of multiple glucose and lactate transporters in astrocytes and neurons were significantly decreased in the cortex and hippocampus of AQP-4 knockout mice. Indeed, AQP-4 knockout mice showed significantly higher accumulation of both glucose and lactate in their brains compared with wild-type mice. Our results show that the deficiency of AQP-4 can cause problems in the metabolic function of astrocytes and lead to cognitive impairment, and that the deficiency of AQP4 in astrocyte endfeet can cause abnormalities in the ANLS system.