Applicability of selected reaction monitoring for precise screening tests.

INTRODUCTION: The proactive identification of diseases through screening tests has long been endorsed as a means to preempt symptomatic onset. However, such screening endeavors are fraught with complications, such as diagnostic inaccuracies, procedural risks, and patient unease during examinations. These challenges are amplified when screenings for multiple diseases are administered concurrently. Selected Reaction Monitoring (SRM) offers a unique advantage, allowing for the high-throughput quantification of hundreds of analytes with minimal interferences. AREAS COVERED: Our research posits that SRM-based assays, traditionally tailored for single-disease biomarker profiling, can be repurposed for multi-disease screening. This innovative approach has the potential to substantially alleviate time, labor, and cost demands on healthcare systems and patients alike. Nonetheless, there are formidable methodological hurdles to overcome. These include difficulties in detecting low-abundance proteins and the risk of model overfitting due to the multiple functionalities of single proteins across different disease spectrums - issues especially pertinent in blood-based assays where detection sensitivity is constrained. As we move forward, technological strides in sample preparation, online extraction, throughput, and automation are expected to ameliorate these limitations. EXPERT OPINION: The maturation of mass spectrometry's integration into clinical laboratories appears imminent, positioning it as an invaluable asset for delivering highly sensitive, reproducible, and precise diagnostic results.

Connectedness rating among commercial pig breeding herds in Korea.

This study aims to estimate the connectedness rating (CR) of Korean swine breeding herds. Using 104,380 performance and 83,200 reproduction records from three swine breeds (Yorkshire, Landrace and Duroc), the CR was estimated for two traits: average daily gain (ADG) and number born alive (NBA) in eight breeding herds in the Republic of Korea (hereafter, Korea). The average CR for ADG in the Yorkshire breed ranges from 1.32% to 28.5% depending on the farm. The average CR for NBA in the Yorkshire herd ranges from 0% to 12.79%. A total of 60% of Yorkshire and Duroc herds satisfied the preconditions suggested for genetic evaluation among the herds. The precondition for the genetic evaluation of CR for ADG, as a productive trait, was higher than 3% and that of NBA, as a reproductive trait, was higher than 1.5%. The ADG in the Yorkshire herds showed the highest average CR. However, the average CR of ADG in the Landrace herds was lower than the criterion of the precondition. The prediction error variance of the difference (PEVD) was employed to assess the validation of the CR, as PEVDs exhibit fluctuations that are coupled with the CR across the herds. A certain degree of connectedness is essential to estimate breeding value comparisons between pig herds. This study suggests that it is possible to evaluate the genetic performance together for ADG and NBA in the Yorkshire herds since the preconditions were satisfied for these four herds. It is also possible to perform a joint genetic analysis of the ADG records of all Duroc herds since the preconditions were also satisfied. This study provides new insight into understanding the genetic connectedness of Korean pig breeding herds. CR could be utilized to accelerate the genetic progress of Korean pig breeding herds.

Delayed Unilateral Facet Interlocking After a Stable Superior Articular Process Fracture of the Cervical Spine: A Case Report.

A 42-year-old man presented with neck pain after a fall from a tree. Spine computed tomography (CT) illustrated the right C5 superior articular process fracture without displacement. Magnetic resonance imaging (MRI) confirmed the fracture and injury of the posterior ligament complex. Initially he was managed conservatively with a neck brace as there were no signs of instability or vertebral body misalignment. However, three days after discharge, right shoulder weakness and numbness of the right upper arm became prominent. X-rays and CT showed anterior slippage of the C4 vertebral body and locked C4/5 facet ??a fractured bony fragment of the C5 superior articular process was pushed forward by the locked inferior articular process of C4 and invaded the neural foramen. Anterior cervical discectomy and fusion (ACDF) was performed using allograft and plate/screws fixation. Although initial imaging showed no evidence of subluxation, surgeons should be aware of occult instability and the possibility of delayed dislocation associated with the unilateral cervical facet fracture.

Sex Difference in the Effect of Bifidobacterium longum on Repeated Water Avoidance Stress-induced Gut Dysbiosis in Wistar Rats.

Dysbiosis in gut microbiota is known to contribute to development of irritable bowel syndrome. We tried to investigate the effect of Bifidobacterium longum on repeated water avoidance stress (WAS) in a Wistar rat model. The three groups (no-stress, WAS, and WAS with B. longum) of rats were allocated to sham or WAS for 1 hour daily for 10 days, and B. longum was administered through gavage for 10 days. Fecal pellet numbers were counted at the end of each 1-hour session of WAS. After 10 days of repeated WAS, the rats were eutanized, and the feces were collected. WAS increased fecal pellet output (FPO) significantly in both sexes (P < 0.001), while the female B. longum group showed significantly decreased FPO (P = 0.005). However, there was no consistent change of myeloperoxidase activity and mRNA expression of interleukin-1ß and TNF-α. Mast cell infiltration at colonic submucosa increased in the female WAS group (P = 0.016). In terms of fecal microbiota, the repeated WAS groups in both sexes showed different beta-diversity compared to control and WAS with B. longum groups. WAS-induced mast cell infiltration was reduced by the administration of B. longum in female rats. Moreover, administration of B. longum relieved WAS-caused dysbiosis, especially in female rats. In conclusion, B. longum was beneficial for WAS-induced stress in rats, especially in females.

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

Determining Quasi-Equilibrium Electron and Hole Distributions of Plasmonic Photocatalysts Using Photomodulated X-ray Absorption Spectroscopy.

Most photocatalytic and photovoltaic devices operate under broadband, constant illumination. Electron and hole dynamics in these devices, however, are usually measured by using ultrafast pulsed lasers in a narrow wavelength range. In this work, we use excited-state X-ray theory originally developed for transient X-ray experiments to study steady-state photomodulated X-ray spectra. We use this method to attempt to extract electron and hole distributions from spectra collected at a nontime-resolved synchrotron beamline. A set of plasmonic metal core-shell nanoparticles is designed as the control experiment because they can systematically isolate photothermal, hot electron, and thermalized electron-hole pairs in a TiO2 shell. Steady-state changes in the Ti L2,3 edge are measured with and without continuous-wave illumination of the nanoparticle's localized surface plasmon resonance. The results suggest that within error the quasi-equilibrium carrier distribution can be determined even from relatively noisy data with mixed excited-state phenomena. Just as importantly, the theoretical analysis of noisy data is used to provide guidelines for the beamline development of photomodulated steady-state spectroscopy.

The Origin and Fate of Liver Myofibroblasts.

Liver fibrosis of different etiologies is a serious health problem worldwide. There is no effective therapy available for liver fibrosis except the removal of the underlying cause of injury or liver transplantation. Development of liver fibrosis is caused by fibrogenic myofibroblasts that are not present in the normal liver, but rather activate from liver resident mesenchymal cells in response to chronic toxic or cholestatic injury. Many studies indicate that liver fibrosis is reversible when the causative agent is removed. Regression of liver fibrosis is associated with the disappearance of activated myofibroblasts and resorption of the fibrous scar. In this review, we discuss the results of genetic tracing and cell fate mapping of hepatic stellate cells and portal fibroblasts, their specific characteristics, and potential phenotypes. We summarize research progress in the understanding of the molecular mechanisms underlying the development and reversibility of liver fibrosis, including activation, apoptosis, and inactivation of myofibroblasts.

MatGD: Materials Graph Digitizer.

We developed Material Graph Digitizer (MatGD), which is a tool for digitizing a data line from scientific graphs. The algorithm behind the tool consists of four steps: (1) identifying graphs within subfigures, (2) separating axes and data sections, (3) discerning the data lines by eliminating irrelevant graph objects and matching with the legend, and (4) data extraction and saving. From the 62,534 papers in the areas of batteries, catalysis, and metal-organic frameworks (MOFs), 501,045 figures were mined. Remarkably, our tool showcased performance with over 99% accuracy in legend marker and text detection. Moreover, its capability for data line separation stood at 66%, which is much higher compared to those of other existing figure-mining tools. We believe that this tool will be integral to collecting both past and future data from publications, and these data can be used to train various machine learning models that can enhance material predictions and new materials discovery.

Evaluation of algal species distributions and prediction of cyanophyte cell counts using statistical techniques.

Safe drinking water sources are crucial for human health. Consequently, water quality management, including continuous monitoring of water quality and algae at sources, is critical to ensure the availability of safe water for local residents. This study aimed to construct statistical prediction models considering probability distributions relevant to cyanophyte cell counts and compare their prediction performance. In this study, water quality parameters at Juam Lake and Tamjin Lake, representative water sources in the Yeongsan and Seomjin rivers, South Korea, were investigated. We used a water quality monitoring network, algae alert system, and hydraulic and hydrological data measured every 7 days from January 2017 to December 2022 from the Water Environment Information System of the National Institute of Environmental Research. Using data for 2017-2021 as a training set and data for 2022 as a test set, the performances of seven models were compared for predicting cyanophyte cell counts. Environmental factors associated with algae in water sources were observed based on the monitoring data, and a prediction model appropriate for the cyanophyte distribution was generated, which also included the risk of toxicity. The extreme gradient boosting with the random forest model had the best predictive performance for cyanophyte cell counts. The study results are expected to facilitate water quality management in various water systems, including water sources.

The Protective Effect of Roseburia faecis Against Repeated Water Avoidance Stress-induced Irritable Bowel Syndrome in a Wister Rat Model.

Roseburia faecis, a butyrate-producing, gram-positive anaerobic bacterium, was evaluated for its usefulness against repeated water avoidance stress (WAS)-induced irritable bowel syndrome (IBS) in a rat model, and the underlying mechanism was explored. We divided the subjects into three groups: one without stress exposure, another subjected to daily 1-hour WAS for 10 days, and a third exposed to the same WAS regimen while also receiving two different R. faecis strains (BBH024 or R22-12-24) via oral gavage for the same 10-day duration. Fecal pellet output (FPO), a toluidine blue assay for mast cell infiltration, and fecal microbiota analyses were conducted using 16S rRNA metagenomic sequencing. Predictive functional profiling of microbial communities in metabolism was also conducted. FPO and colonic mucosal mast cell counts were significantly higher in the WAS group than in the control group (male, P = 0.004; female, P = 0.027). The administration of both BBH024 (male, P = 0.015; female, P = 0.022) and R22-12-24 (male, P = 0.003; female, P = 0.040) significantly reduced FPO. Submucosal mast cell infiltration in the colon showed a similar pattern in males. In case of fecal microbiota, the WAS with R. faecis group showed increased abundance of the Roseburia genus compared to WAS alone. Moreover, the expression of a gene encoding a D-methionine transport system substrate-binding protein was significantly elevated in the WAS with R. faecis group compared to that in the WAS (male, P = 0.028; female, P = 0.025) group. These results indicate that R. faecis is a useful probiotic for treating IBS and colonic microinflammation.

Regulation of astrocyte activity and immune response on graphene oxide-coated titanium by electrophoretic deposition.

Introduction: Astrocytes play crucial role in modulating immune response in the damaged central nervous system. Numerous studies have investigated the relationship between immune responses in astrocytes and brain diseases. However, the potential application of nanomaterials for alleviating neuroinflammation induced by astrocytes remains unexplored. Method: In this study, we utilized electrophoretic deposition (EPD) to coat graphene oxide (GO) onto titanium (Ti) to enhance the bioactivity of Ti. Results: We confirmed that GO-Ti could improve cell adhesion and proliferation of astrocytes with upregulated integrins and glial fibrillary acidic protein (GFAP) expression. Moreover, we observed that astrocytes on GO-Ti exhibited a heightened immune response when exposed to lipopolysaccharide (LPS). Although pro-inflammatory cytokines increased, anti-inflammatory cytokines and brain-derived neurotrophic factors involved in neuroprotective effects were also augmented through nuclear localization of the yes-associated protein (YAP) and nuclear factor kappa B (NF-κB). Discussion: Taken together, GO-Ti could enhance the neuroprotective function of astrocytes by upregulating the expression of anti-inflammatory cytokines and neuroprotective factors with improved cell adhesion and viability. Consequently, our findings suggest that GO-Ti has the potential to induce neuroprotective effects by regulating cell activity.

Mefenamic Acid-Upregulated Nrf2/SQSTM1 Protects Hepatocytes against Oxidative Stress-Induced Cell Damage.

Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent antioxidant properties and a neuroprotective effect against oxidative stress. However, its impact on the liver is unclear. This study aimed to elucidate the antioxidative effects of MFA and their underlying mechanisms. We observed that MFA treatment upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Treatment with various anthranilic acid derivative-class NSAIDs, including MFA, increased the expression of sequestosome 1 (SQSTM1) in HepG2 cells. MFA disrupted the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, activating the Nrf2 signaling pathway. SQTM1 knockdown experiments revealed that the effect of MFA on the Nrf2 pathway was masked in the absence of SQSTM1. To assess the cytoprotective effect of MFA, we employed tert-Butyl hydroperoxide (tBHP) as a ROS inducer. Notably, MFA exhibited a protective effect against tBHP-induced cytotoxicity in HepG2 cells. This cytoprotective effect was abolished when SQSTM1 was knocked down, suggesting the involvement of SQSTM1 in mediating the protective effect of MFA against tBHP-induced toxicity. In conclusion, this study demonstrated that MFA exhibits cytoprotective effects by upregulating SQSTM1 and activating the Nrf2 pathway. These findings improve our understanding of the pharmacological actions of MFA and highlight its potential as a therapeutic agent for oxidative stress-related conditions.

Literature-based predictions of Mendelian disease therapies.

In the effort to treat Mendelian disorders, correcting the underlying molecular imbalance may be more effective than symptomatic treatment. Identifying treatments that might accomplish this goal requires extensive and up-to-date knowledge of molecular pathways-including drug-gene and gene-gene relationships. To address this challenge, we present "parsing modifiers via article annotations" (PARMESAN), a computational tool that searches PubMed and PubMed Central for information to assemble these relationships into a central knowledge base. PARMESAN then predicts putatively novel drug-gene relationships, assigning an evidence-based score to each prediction. We compare PARMESAN's drug-gene predictions to all of the drug-gene relationships displayed by the Drug-Gene Interaction Database (DGIdb) and show that higher-scoring relationship predictions are more likely to match the directionality (up- versus down-regulation) indicated by this database. PARMESAN had more than 200,000 drug predictions scoring above 8 (as one example cutoff), for more than 3,700 genes. Among these predicted relationships, 210 were registered in DGIdb and 201 (96%) had matching directionality. This publicly available tool provides an automated way to prioritize drug screens to target the most-promising drugs to test, thereby saving time and resources in the development of therapeutics for genetic disorders.

Using electron energy-loss spectroscopy to measure nanoscale electronic and vibrational dynamics in a TEM.

Electron energy-loss spectroscopy (EELS) can measure similar information to x-ray, UV-Vis, and IR spectroscopies but with atomic resolution and increased scattering cross-sections. Recent advances in electron monochromators have expanded EELS capabilities from chemical identification to the realms of synchrotron-level core-loss measurements and to low-loss, 10-100 meV excitations, such as phonons, excitons, and valence structures. EELS measurements are easily correlated with electron diffraction and atomic-scale real-space imaging in a transmission electron microscope (TEM) to provide detailed local pictures of quasiparticle and bonding states. This perspective provides an overview of existing high-resolution EELS (HR-EELS) capabilities while also motivating the powerful next step in the field-ultrafast EELS in a TEM. Ultrafast EELS aims to combine atomic-level, element-specific, and correlated temporal measurements to better understand spatially specific excited-state phenomena. Ultrafast EELS measurements also add to the abilities of steady-state HR-EELS by being able to image the electromagnetic field and use electrons to excite photon-forbidden and momentum-specific transitions. We discuss the technical challenges ultrafast HR-EELS currently faces, as well as how integration with in situ and cryo measurements could expand the technique to new systems of interest, especially molecular and biological samples.

Multispectral sensor fusion in SmartWatch for in situ continuous monitoring of human skin hydration and body sweat loss.

Post-pandemic health operations have become a near-term reality, discussions around wearables are on the rise. How do wearable health solutions effectively deploy and use this opportunity to fill the gap between wellness and healthcare? In this paper, we will talk about wearable healthcare diagnosis, with a particular focus on monitoring skin hydration using optical multi-wavelength sensor fusion. Continuous monitoring of human skin hydration is a task of paramount importance for maintaining water loss dynamics for fitness lovers as well as for skin beauty, integrity and the health of the entire body. Preserving the appropriate levels of hydration ensures consistency of weight, positively affects psychological state, and proven to result in a decrease in blood pressure as well as the levels of "bad" cholesterol while slowing down the aging processes. Traditional methods for determining the state of water content in the skin do not allow continuous and non-invasive monitoring, which is required for variety of consumer, clinical and cosmetic applications. We present novel sensing technology and a pipeline for capturing, modeling and analysis of the skin hydration phenomena and associated changes therein. By expanding sensing capabilities built into the SmartWatch sensor and combining them with advanced modeling and Machine Learning (ML) algorithms, we identified several important characteristics of photoplethysmography (PPG) signal and spectral sensitivity corresponding to dynamics of skin water content. In a hardware aspect, we newly propose the expansion of SmartWatch capabilities with InfraRed light sources equipped with wavelengths of 970 nm and 1450 nm. Evaluation of the accuracy and characteristics of PPG sensors has been performed with biomedical optics-based simulation framework using Monte Carlo simulations. We performed rigorous validation of the developed technology using experimental and clinical studies. The developed pipeline serves as a tool in the ongoing studies of the next generation of optical sensing technology.

Chaperone-mediated autophagy dysregulation during aging impairs hepatic fatty acid oxidation via accumulation of NCoR1.

OBJECTIVE: Alterations in lipid metabolism are associated with aging and age-related diseases. Chaperone-mediated autophagy (CMA) is a lysosome-dependent process involved in specific protein degradation. Heat shock cognate 71 kDa protein (Hsc70) recognizes cytosolic proteins with KFERQ motif and allows them to enter the lysosome via lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A). CMA deficiency is associated with dysregulated lipid metabolism in the liver. In this study, we examined the effect of CMA on lipid metabolism in the aged liver. METHODS: 12-week-old and 88-week-old mice were employed to assess the effect of aging on hepatic CMA activity. We generated CMA-deficient mouse primary hepatocytes using siRNA for Lamp2a and liver-specific LAMP2A knockdown mice via adeno-associated viruses expressing short hairpin RNAs to investigate the influence of CMA on lipid metabolism. RESULTS: We noted aging-induced progression toward fatty liver and a decrease in LAMP2A levels in total protein and lysosomes. The expression of genes associated with fatty acid oxidation was markedly downregulated in the aged liver, as verified in CMA-deficient mouse primary hepatocytes. In addition, the aged liver accumulated nuclear receptor corepressor 1 (NCoR1), a negative regulator of peroxisome proliferator-activated receptor α (PPARα). We found that Hsc70 binds to NCoR1 via the KFERQ motif. Lamp2a siRNA treatment accumulated NCoR1 and decreased the fatty acid oxidation rate. Pharmacological activation of CMA by AR7 treatment increased LAMP2A expression, leading to NCoR1 degradation. A liver-specific LAMP2A knockdown via adeno-associated viruses expressing short hairpin RNAs caused NCoR1 accumulation, inactivated PPARα, downregulated the expression of fatty acid oxidation-related genes and significantly increased liver triglyceride levels. CONCLUSIONS: Our results elucidated a novel PPARα regulatory mechanism involving CMA-mediated NCoR1 degradation during aging. These findings demonstrate that CMA dysregulation is crucial for the progression of aging-related fatty liver diseases.

Ruptured Fusiform Anterior Cerebral Artery Aneurysm in an Infant : Case Report and a Literature Review.

Ruptured intracranial aneurysms in infants are rare and infantile fusiform anterior cerebral artery (ACA) aneurysms are much rarer. In this report, we described the case of a 7-month-old infant with a ruptured fusiform ACA aneurysm who presented with seizure and underwent endovascular treatment. The patient was initially in a coma and the neurologic condition did not improve after treatment. The clinical characteristics of the case and literature review were discussed.

Capacitive Electrode-Based Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic AD Mouse Models: The Electroceutical Targeting of Alzheimer's Disease Feasibility Study.

Iron accumulation in the brain accelerates Alzheimer's disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aß fibril structure or the Aß plaque in a mouse model of Alzheimer's disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe3O4) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7-1.4 V/cm on a magnetite-bound Aß-fibril or a transgenic Alzheimer's disease (AD) mouse model revealed the degradation of the Aß fibril or the removal of the Aß-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

Necessity of an Integrative Animal Model for a Comprehensive Study of Attention-Deficit/Hyperactivity Disorder.

Animal models of attention-deficit/hyperactivity disorder (ADHD) have been used to study and understand the behavioral, neural, and physiological mechanisms underlying ADHD. These models allow researchers to conduct controlled experiments and manipulate specific brain regions or neurotransmitter systems to investigate the underlying causes of ADHD and test potential drug targets or treatments. However, it is essential to note that while these models can provide valuable insights, they do not ideally mimic the complex and heterogeneous nature of ADHD and should be interpreted cautiously. Additionally, since ADHD is a multifactorial disorder, environmental and epigenetic factors should be considered simultaneously. In this review, the animal models of ADHD reported thus far are classified into genetic, pharmacological, and environmental models, and the limitations of the representative models are discussed. Furthermore, we provide insights into a more reliable alternative model for the comprehensive study of ADHD.

Sex and Age-Dependent Olfactory Memory Dysfunction in ADHD Model Mice.

ADHD is a typical neurodevelopmental disorder with a high prevalence rate. NSCs in the subventricular zone (SVZ) are closely related to neurodevelopmental disorder and can affect olfactory function by neurogenesis and migratory route. Although olfactory dysfunction is one of the symptoms of ADHD, the relevance of cells in the olfactory bulb derived from NSCs has not been studied. Therefore, we investigated olfactory memory and NSCs in Git1-deficient mice, under the ADHD model. Interestingly, only adult male G protein-coupled receptor kinase-interacting protein-1 (GIT1)-deficient (+/-, HE) mice showed impaired olfactory memory, suggesting sex and age dependence. We performed adult NSCs culture from the SVZ and observed distinct cell population in both sex and genotype. Taken together, our study suggests that the altered differentiation of NSCs in GIT1+/- mice can contribute to olfactory dysfunction in ADHD.