Preliminary research on tailored fluid therapy in pigs: comparing customized ionic solutions with Hartmann's solution.

BACKGROUND: Fluid therapy in veterinary medicine is pivotal for treating various conditions in pigs; however, standard solutions, such as Hartmann's solution, may not optimally align with pig physiology. This study explored the development and efficacy of a customized fluid therapy tailored to the ionic concentrations of pig blood, aiming to enhance treatment outcomes and safety in both healthy and diseased pigs. RESULTS: The study involved two experiments: the first to assess the safety and stability of customized fluids in healthy pigs, and the second to evaluate the efficacy in pigs with clinical symptoms of dehydration. In healthy pigs, the administration of customized fluids showed no adverse effects, with slight alterations observed in pO2, hematocrit, and glucose levels in some groups. In symptomatic pigs, the customized fluid group did not show any improvement in clinical symptoms, with no significant changes in blood chemistry or metabolite levels compared to controls. The customized fluid group showed a mild increase in some values after administration, yet within normal physiological ranges. The study reported no significant improvements in clinical or dehydration status, attributing the observed variations in blood test results to the limited sample size and anaesthesia effects rather than fluid characteristics. CONCLUSIONS: Customized fluid therapy, tailored to mimic the ionic concentrations of pig blood, appears to be a safe and potentially more effective alternative to conventional solutions such as Hartmann's solution for treating pigs under various health conditions. Further research with larger sample sizes and controlled conditions is recommended to validate these findings and to explore the full potential of customized fluid therapy in veterinary practice.

BattleSound: A Game Sound Benchmark for the Sound-Specific Feedback Generation in a Battle Game.

A haptic sensor coupled to a gamepad or headset is frequently used to enhance the sense of immersion for game players. However, providing haptic feedback for appropriate sound effects involves specialized audio engineering techniques to identify target sounds that vary according to the game. We propose a deep learning-based method for sound event detection (SED) to determine the optimal timing of haptic feedback in extremely noisy environments. To accomplish this, we introduce the BattleSound dataset, which contains a large volume of game sound recordings of game effects and other distracting sounds, including voice chats from a PlayerUnknown's Battlegrounds (PUBG) game. Given the highly noisy and distracting nature of war-game environments, we set the annotation interval to 0.5 s, which is significantly shorter than the existing benchmarks for SED, to increase the likelihood that the annotated label contains sound from a single source. As a baseline, we adopt mobile-sized deep learning models to perform two tasks: weapon sound event detection (WSED) and voice chat activity detection (VCAD). The accuracy of the models trained on BattleSound was greater than 90% for both tasks; thus, BattleSound enables real-time game sound recognition in noisy environments via deep learning. In addition, we demonstrated that performance degraded significantly when the annotation interval was greater than 0.5 s, indicating that the BattleSound with short annotation intervals is advantageous for SED applications that demand real-time inferences.

Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis.

Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2-, SDC1-, or heparan sulfate 2-O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)-stimulated FGFR1- v-akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin- and caveolin-mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1-AKT-p53-p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1-AKT-p53-p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1-AKT-p53-p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis.

Inflammasome-mediated Inflammation by Malassezia in human keratinocytes: A comparative analysis with different strains.

Malassezia species are associated with several common dermatologic conditions including pityriasis versicolor, seborrhoeic dermatitis, folliculitis, and atopic dermatitis and dandruff. However, its causal role remains to be established. We intended to explore the role of inflammasome activation in human keratinocytes in response to three different Malassezia species. We compared the different activation patterns of inflammasomes and the expression of pro-inflammatory cytokines and antimicrobial peptides by three different Malassezia species-M. restricta, M. globosa and M. sympodialis-in human keratinocytes. We found that different Malassezia species, especially M. restricta and M. globosa could induce nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin-domain-containing protein (NLRP)3-apoptosis-associated speck-like protein containing CARD (ASC) inflammasome activation and subsequent interleukin (IL)-1ß secretion in human keratinocytes. Malassezia species variably induced thymic stromal lymphopoietin, ß-defensin 2, and LL-37. IL-8 mRNA and IL-22 protein significantly increased in the M. sympodialis-treated group, and Chemokine C-C motif ligand (CCL)17 and CCL22 mRNA were increased in response to M. globosa- and M. restricta- treated keratinocytes, respectively. Our data show that various species of Malassezia promote variable inflammatory responses in keratinocytes by activating NLRP3 inflammasomes, pro-inflammatory cytokines and chemokines, and antimicrobial peptides.

Pilot study of a single-channel EEG seizure detection algorithm using machine learning.

OBJECTIVE: Seizures are one of the most common emergencies in the neonatal intensive care unit (NICU). They are identified through visual inspection of electroencephalography (EEG) reports and treated by neurophysiologic experts. To support clinical seizure detection, several feature-based automatic neonatal seizure detection algorithms have been proposed. However, as they were unsuitable for clinical application due to their low accuracy, we developed a new seizure detection algorithm using machine learning for single-channel EEG to overcome these limitations. METHODS: The dataset applied in our algorithm contains EEG recordings from human neonates. A 19-channel EEG system recorded the brain waves of 79 term neonates admitted to the NICU at the Helsinki University Hospital. From these datasets, we selected six patients with conformational seizure annotations for the pilot study and allocated four and two patients for our training and testing datasets, respectively. The presence of seizures in the EEGs was annotated independently by three experts through visual interpretation. We divided the data into epochs of 5 s each and further defined a seizure block to label the annotations from each expert recorded every second. Subsequently, to create a balanced dataset, any data point with a non-seizure label was moved to the training and test dataset. RESULT: The developed principal component feature-extracted machine learning algorithm used 62.5% of the relative time (only 5 s for decision) of the baseline, reaching an area under the ROC curve score of 0.91. The effect of diversified parameters was meticulously examined, and 100 principal components were extracted to optimize the model performance. CONCLUSION: Our machine learning-based seizure detection algorithm exhibited the potential for clinical application in NICUs, general wards, and at home and proved its convenience by requiring only a single channel for implementation.

Autophagy in Neurodegenerative Diseases: A Hunter for Aggregates.

Cells have developed elaborate quality-control mechanisms for proteins and organelles to maintain cellular homeostasis. Such quality-control mechanisms are maintained by conformational folding via molecular chaperones and by degradation through the ubiquitin-proteasome or autophagy-lysosome system. Accumulating evidence suggests that impaired autophagy contributes to the accumulation of intracellular inclusion bodies consisting of misfolded proteins, which is a hallmark of most neurodegenerative diseases. In addition, genetic mutations in core autophagy-related genes have been reported to be linked to neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Conversely, the pathogenic proteins, such as amyloid ß and α-synuclein, are detrimental to the autophagy pathway. Here, we review the recent advances in understanding the relationship between autophagic defects and the pathogenesis of neurodegenerative diseases and suggest autophagy induction as a promising strategy for the treatment of these conditions.

Contribution of Autophagy-Notch1-Mediated NLRP3 Inflammasome Activation to Chronic Inflammation and Fibrosis in Keloid Fibroblasts.

Keloid is a representative chronic fibroproliferative condition that occurs after tissue injury. Emerging evidence showed that activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the pro-inflammatory response in injured tissues. However, the role of NLRP3 inflammasome in keloid progression remains unclear. Notch signaling, which activates NLRP3 inflammasome, is known to contribute to scar formation in keloid, but the cause of enhanced Notch signaling in keloid is not clear. We sought to investigate whether autophagy regulates Notch1 signaling in keloid fibroblasts and determine whether Notch1 signaling might regulate NLRP3 inflammasomes and myofibroblast differentiation. An in vitro model of keloid was established by culturing primary keloid fibroblasts from patients. Expression levels of Notch1, NLRP3 inflammasome proteins, pro-inflammatory cytokines, and myofibroblast markers in keloid fibroblasts were examined and compared with those in normal fibroblasts. Autophagy known to mediate Notch1 degradation was also monitored in fibroblasts. Small interfering RNA (siRNA) targeting Notch1 was used to transfect keloid fibroblasts to further examine the role of Notch signaling in NLRP3 inflammasome activation. Expression levels of Notch1 and NLRP3 inflammasome in keloid fibroblasts increased compared to those in normal fibroblasts. Such increases were accompanied by increased LC3 levels and reduced autophagic flux. Notch1 silencing in keloid fibroblasts by siRNA transfection significantly suppressed increased levels of overall NLRP3 inflammasome complex proteins, NF-kB, and α-smooth muscle actin. Autophagy induction by rapamycin treatment in keloid fibroblasts effectively suppressed expression levels of Notch1 and NLRP3 inflammasome proteins. Decreased autophagy activity in keloid can result in Notch1-mediated myofibroblast activation and NLRP3 inflammasome signaling activation which is critical for chronic inflammation. Collectively, these results identify Notch1 as a novel activator of NLRP3 inflammasome signaling leading to chronic tissue damage and myofibroblast differentiation in keloid progression.

Extracellular Vesicle as a Source of Alzheimer's Biomarkers: Opportunities and Challenges.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aß) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry.

Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.

Hereditary spastic paraplegias are inherited neurological disorders characterized by progressive lower-limb spasticity and weakness. Although more than 50 genetic loci are known [spastic gait (SPG)1 to -57], over half of hereditary spastic paraplegia cases are caused by pathogenic mutations in four genes encoding proteins that function in tubular endoplasmic reticulum (ER) network formation: atlastin-1 (SPG3A), spastin (SPG4), reticulon 2 (SPG12), and receptor expression-enhancing protein 1 (SPG31). Here, we show that the SPG33 protein protrudin contains hydrophobic, intramembrane hairpin domains, interacts with tubular ER proteins, and functions in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections. Protrudin also interacts with KIF5 and harbors a Rab-binding domain, a noncanonical FYVE (Fab-1, YGL023, Vps27, and EEA1) domain, and a two phenylalanines in an acidic tract (FFAT) domain and, thus, may also function in the distribution of ER tubules via ER contacts with the plasma membrane or other organelles.

Analysis of blood composition by porcine breeding cycle.

BACKGROUND: Pigs for biomedical research are administered commercial fluids made for human consumption when they receive intravenous (IV) fluid therapy. Although pigs and humans have slightly different bodily fluid compositions, the composition shift happens at the same rate as their rapid growth. OBJECTIVE: The study aimed to analyse the composition of porcine blood according to breeding cycle using a portable blood analyser and provides data for developing customized IV fluids for pigs. METHODS: Pigs were sorted 25, 50, 100 and 120 days after birth, and sows were classified into candidate, pregnant and farrowing groups. A blood sample was collected from the external jugular vein and analysed using the EPOC blood analysis system using haematological, biochemical and gas parameters. RESULTS: There was no difference among pig groups by age, but hematocrit and haemoglobin amounts decreased in sows after farrowing, but their concentrations were higher as compared to pigs. Glucose gradually reduced as age increased in pigs and during pregnancy in sows. CONCLUSION: This study provided a comprehensive analysis of porcine blood composition by breeding cycle and highlighted the importance of glucose supplementation for IV fluid therapy in pigs.

Optimization of electrochemical regeneration of intercalated MXene for the adsorptive removal of ciprofloxacin: Prospective mechanism.

2D-Ti3C2Tx MXene nanosheets intercalated with sodium ions (SI-Ti3C2Tx) were synthesized and utilized in simultaneous adsorption and electrochemical regeneration with ciprofloxacin (CPX). The primary focus of this study is to investigate the long-term stability of SI-Ti3C2Tx MXene and to propose the underlying regeneration mechanisms. The successful synthesis of Ti3AlC2, Ti3C2Tx MXene, and SI-Ti3C2Tx MXene was confirmed using X-ray diffraction, X-ray photoelectron spectroscopy, and Raman spectroscopy. Electrochemical regeneration parameters such as charge passed, regeneration time, current density, and electrolyte composition were optimized with values of 787.5 C g-1, 7.5 min, 10 mA cm-2, and 2.5w/v% sodium chloride, respectively, enabling the complete regeneration of the SI-Ti3C2Tx MXene. In addition, the electrochemical regeneration significantly enhanced CPX removal from the SI-Ti3C2Tx MXene owing to partial amorphization, disorderliness, increased functional groups, delamination, and defect creation in the structure. Thus, the synthesized nano-adsorbent has proven helpful in practical water treatment with optimized electrochemical regeneration processes.

Antioxidant Effects of Myo-Inositol Improve the Function and Fertility of Cryopreserved Boar Semen.

During cryopreservation, sperm undergoes structural and molecular changes such as ice crystal formation, DNA fragmentation, and reactive oxygen species (ROS) production, leading to decreased sperm quality after thawing. Antioxidants play a crucial role in preventing these damages, both in vivo and in vitro. One potent antioxidant is myo-inositol, known for its protective effects on sperm against ROS. This study aimed to investigate the protective effect of myo-inositol on cryopreserved boar semen. The semen was diluted, cooled, and cryopreserved using a BF5 extender. It was then divided into five groups: control and different concentrations of myo-inositol (0.5, 1, 1.5, and 2 mg/mL). The post-thaw evaluation included assessments of motility, viability, acrosome integrity, mitochondrial membrane potential (MMP), caspase activity, gene expression, ROS levels, apoptosis, and IVF with treated semen. Results showed that myo-inositol at 0.5 mg/mL improved motility, acrosome integrity, and fertilization ability. It also reduced the expression of pro-apoptotic genes and increased SMCP expression. Lower concentrations also demonstrated improved viability and reduced apoptosis and ROS levels. In conclusion, myo-inositol treatment during cryopreservation improved sperm quality, reduced apoptosis and ROS levels, and enhanced fertility rates in boar semen.

Enhanced biodegradation of perfluorooctanoic acid in a dual biocatalyzed microbial electrosynthesis system.

The toxic perfluorooctanoic acid (PFOA) is widely spread in terrestrial and aquatic habitats owing to its resistance to conventional degradation processes. Advanced techniques to degrade PFOA requires drastic conditions with high energy cost. In this study, we investigated PFOA biodegradation in a simple dual biocatalyzed microbial electrosynthesis system (MES). Different PFOA loadings (1, 5, and 10 ppm) were tested and a biodegradation of 91% was observed within 120 h. Propionate production improved and short-carbon-chain PFOA intermediates were detected, which confirmed PFOA biodegradation. However, the current density decreased, indicating an inhibitory effect of PFOA. High-throughput biofilm analysis revealed that PFOA regulated the microbial flora. Microbial community analysis showed enrichment of the more resilient and PFOA adaptive microbes, including Methanosarcina and Petrimonas. Our study promotes the potential use of dual biocatalyzed MES system as an environment-friendly and inexpensive method to remediate PFOA and provides a new direction for bioremediation research.

TRIM22 facilitates autophagosome-lysosome fusion by mediating the association of GABARAPs and PLEKHM1.

Tripartite motif (TRIM) proteins are a large family of E3 ubiquitin ligases implicated in antiviral defense systems, tumorigenesis, and protein quality control. TRIM proteins contribute to protein quality control by regulating the ubiquitin-proteasome system, endoplasmic reticulum-associated degradation, and macroautophagy/autophagy. However, the detailed mechanisms through which various TRIM proteins regulate downstream events have not yet been fully elucidated. Herein, we identified a novel function of TRIM22 in the regulation of autophagy. TRIM22 promotes autophagosome-lysosome fusion by mediating the association of GABARAP family proteins with PLEKHM1, thereby inducing the autophagic clearance of protein aggregates, independent of its E3 ubiquitin ligase activity. Furthermore, a TRIM22 variant associated with early-onset familial Alzheimer disease interferes with autophagosome-lysosome fusion and autophagic clearance. These findings suggest TRIM22 as a critical autophagic regulator that orchestrates autophagosome-lysosome fusion by scaffolding autophagy-related proteins, thus representing a potential therapeutic target in neurodegenerative diseases.Abbreviations: AD: Alzheimer disease; ADAOO: AD age of onset; AICD: APP intracellular domain; APP: amyloid beta precursor protein; BSA: bovine serum albumin; cDNAs: complementary DNAs; CQ: chloroquine; CTF: carboxyl-terminal fragment; EBSS: Earle's balanced salt solution; GABARAP: GABA type A receptor-associated protein; GST: glutathione S-transferase; HA: hemagglutinin; HOPS: homotypic fusion and protein sorting; IFN: interferon; IL1A/IL-1α: interleukin 1 alpha; KO: knockout; MTORC1: mechanistic target of rapamycin kinase complex 1; NFKBIA/IκBα: NFKB inhibitor alpha; NFE2L2/NRF2: NFE2 like bZIP transcription factor; PBS: phosphate-buffered saline; PI3K: class I phosphoinositide 3-kinase; PLA: proximity ligation assay; PLEKHM1: pleckstrin homology and RUN domain containing M1; PSEN1: presenilin 1; SEM: standard errors of the means; SNAREs: soluble N-ethylmaleimide-sensitive factor attachment protein receptors; SNCA: synuclein alpha; SNP: single nucleotide polymorphism; TBS: tris-buffered saline; TNF/TNF-α: tumor necrosis factor; TRIM: tripartite motif; ULK1: unc-51 like autophagy activating kinase 1; WT: wild-type.

Protective effect of TPP-Niacin on microgravity-induced oxidative stress and mitochondrial dysfunction of retinal epithelial cells.

Adverse effects of spaceflight on the human body are attritubuted to microgravity and space radiation. One of the most sensitive organs affected by them is the eye, particularly the retina. The conditions that astronauts suffer, such as visual acuity, is collectively called a spaceflight-associated neuro-ocular syndrome (SANS); however, the underlying molecular mechanism of the microgravity-induced ocular pathogenesis is not clearly understood. The current study explored how microgravity affects the retina function in ARPE19 cells in vitro under time-averaged simulated microgravity (µG) generated by clinostat. We found multicellular spheroid (MCS) formation and a significantly decreased cell migration potency under µG conditions compared to 1G in ARPE19 cells. We also observed that µG increases intracellular reactive oxygen species (ROS) and causes mitochondrial dysfunction in ARPE19 cells. Subsequently, we showed that µG activates autophagic pathways and ciliogenesis. Furthermore, we demonstrated that mitophagy activation is triggered via the mTOR-ULK1-BNIP3 signaling axis. Finally, we validated the effectiveness of TPP-Niacin in mitigating µG-induced oxidative stress and mitochondrial dysfunction in vitro, which provides the first experimental evidence for TPP-Niacin as a potential therapeutic agent to ameliorate the cellular phenotypes caused by µG in ARPE19 cells. Further investigations are, however, required to determine its physiological functions and biological efficacies in primary human retinal cells, in vivo models, and target identification.

Autophagy: Guardian of Skin Barrier.

Autophagy is a major degradation pathway that removes harmful intracellular substances to maintain homeostasis. Various stressors, such as starvation and oxidative stress, upregulate autophagy, and the dysregulation of autophagy is associated with various human diseases, including cancer and skin diseases. The skin is the first defense barrier against external environmental hazards such as invading pathogens, ultraviolet rays, chemical toxins, and heat. Although the skin is exposed to various stressors that can activate autophagy, the roles of autophagy in the skin have not yet been fully elucidated. Accumulating evidence suggests that autophagy is closely associated with pathogenesis and the treatment of immune-related skin diseases. In this study, we review how autophagy interacts with skin cells, including keratinocytes and immune cells, enabling them to successfully perform their protective functions by eliminating pathogens and maintaining skin homeostasis. Furthermore, we discuss the implications of autophagy in immune-related skin diseases, such as alopecia areata, psoriasis, and atopic dermatitis, and suggest that a combination of autophagy modulators with conventional therapies may be a better strategy for the treatment of these diseases.

Development of Alzheimer's Disease Biomarkers: From CSF- to Blood-Based Biomarkers.

In the 115 years since the discovery of Alzheimer's disease (AD), our knowledge, diagnosis, and therapeutics have significantly improved. Biomarkers are the primary tools for clinical research, diagnostics, and therapeutic monitoring in clinical trials. They provide much insightful information, and while they are not clinically used routinely, they help us to understand the mechanisms of this disease. This review charts the journey of AD biomarker discovery and development from cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aß42), total tau (T-tau), and phosphorylated tau (p-tau) biomarkers and imaging technologies to the next generation of biomarkers. We also discuss advanced high-sensitivity assay platforms for CSF Aß42, T-tau, p-tau, and blood analysis. The recently proposed Aß deposition/tau biomarker/neurodegeneration or neuronal injury (ATN) scheme might facilitate the definition of the biological status underpinning AD and offer a common language among researchers across biochemical biomarkers and imaging. Moreover, we highlight blood-based biomarkers for AD that offer a scalable alternative to CSF biomarkers through cost-saving and reduced invasiveness, and may provide an understanding of disease initiation and development. We discuss different groups of blood-based biomarker candidates, their advantages and limitations, and paths forward, from identification and analysis to clinical validation. The development of valid blood-based biomarkers may facilitate the implementation of future AD therapeutics and diagnostics.

General-Purpose Ultrasound Neuromodulation System for Chronic, Closed-Loop Preclinical Studies in Freely Behaving Rodents.

Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head-fixed, anesthesia-dependent, and acute, limiting clinical translatability. Here, this work reports a general-purpose ultrasound neuromodulation system for chronic, closed-loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact-free stimulation and simultaneous neural recording. Using the general-purpose system, it can be observed that state-dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption.

Intersection between Redox Homeostasis and Autophagy: Valuable Insights into Neurodegeneration.

Autophagy, a main degradation pathway for maintaining cellular homeostasis, and redox homeostasis have recently been considered to play protective roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Increased levels of reactive oxygen species (ROS) in neurons can induce mitochondrial damage and protein aggregation, thereby resulting in neurodegeneration. Oxidative stress is one of the major activation signals for the induction of autophagy. Upon activation, autophagy can remove ROS, damaged mitochondria, and aggregated proteins from the cells. Thus, autophagy can be an effective strategy to maintain redox homeostasis in the brain. However, the interaction between redox homeostasis and autophagy is not clearly elucidated. In this review, we discuss recent studies on the relationship between redox homeostasis and autophagy associated with neurodegenerative diseases and propose that autophagy induction through pharmacological intervention or genetic activation might be a promising strategy to treat these disorders.

Identification of Cathepsin D as a Plasma Biomarker for Alzheimer's Disease.

Although Alzheimer's disease (AD) is the most common neurodegenerative disease, there are still no drugs available to treat or prevent AD effectively. Here, we examined changes in levels of selected proteins implicated in the pathogenesis of AD using plasma samples of control subjects and patients with cognition impairment. To precisely categorize the disease, fifty-six participants were examined with clinical cognitive tests, amyloid positron emission tomography (PET) scan, and white matter hyperintensities scored by magnetic resonance imaging. Plasma cathepsin D levels of the subjects were examined by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Correlation of plasma cathepsin D levels with AD-related factors and clinical characteristics were examined by statistical analysis. By analyzing quantitative immunoblot and ELISA, we found that the plasma level of cathepsin D, a major lysosomal protease, was decreased in the group with amyloid plaque deposition at the brain compared to the control group. The level of plasma cathepsin D was negatively correlated with clinical dementia rating scale sum of boxes (CDR-SB) scores. In addition, our integrated multivariable logistic regression model suggests the high performance of plasma cathepsin D level for discriminating AD from non-AD. These results suggest that the plasma cathepsin D level could be developed as a diagnostic biomarker candidate for AD.