Recent advances in two-dimensional materials for the diagnosis and treatment of neurodegenerative diseases.

With the size of the aging population increasing worldwide, the effective diagnosis and treatment of neurodegenerative diseases (NDDs) has become more important. Two-dimensional (2D) materials offer specific advantages for the diagnosis and treatment of NDDs due to their high sensitivity, selectivity, stability, and biocompatibility, as well as their excellent physical and chemical characteristics. As such, 2D materials offer a promising avenue for the development of highly sensitive, selective, and biocompatible theragnostics. This review provides an interdisciplinary overview of advanced 2D materials and their use in biosensors, drug delivery, and tissue engineering/regenerative medicine for the diagnosis and/or treatment of NDDs. The development of 2D material-based biosensors has enabled the early detection and monitoring of NDDs via the precise detection of biomarkers or biological changes, while 2D material-based drug delivery systems offer the targeted and controlled release of therapeutics to the brain, crossing the blood-brain barrier and enhancing treatment effectiveness. In addition, when used in tissue engineering and regenerative medicine, 2D materials facilitate cell growth, differentiation, and tissue regeneration to restore neuronal functions and repair damaged neural networks. Overall, 2D materials show great promise for use in the advanced treatment of NDDs, thus improving the quality of life for patients in an aging population.

Stimuli-Responsive Polymer Actuator for Soft Robotics.

Polymer actuators are promising, as they are widely used in various fields, such as sensors and soft robotics, for their unique properties, such as their ability to form high-quality films, sensitivity, and flexibility. In recent years, advances in structural and fabrication processes have significantly improved the reliability of polymer sensing-based actuators. Polymer actuators have attracted considerable attention for use in artificial or biohybrid systems, as they have the potential to operate under diverse conditions with high durability. This review briefly describes different types of polymer actuators and provides an understanding of their working mechanisms. It focuses on actuation modes controlled by diverse or multiple stimuli. Furthermore, it discusses the fabrication processes of polymer actuators; the fabrication process is an important consideration in the development of high-quality actuators with sensing properties for a wide range of applications in soft robotics. Additionally, the high potential of polymer actuators for use in sensing technology is examined, and the latest developments in the field of polymer actuators, such as the development of biohybrid polymers and the use of polymer actuators in 4D printing, are briefly described.

Comprehensive analysis of somatic mutations and structural variations in domestic pig.

Understanding somatic mutations and structural variations in domestic pigs (Sus scrofa domestica) is critical due to their increasing importance as model organisms in biomedical research. In this study, we conducted a comprehensive analysis through whole-genome sequencing of skin, organs, and blood samples. By examining two pig pedigrees, we investigated the inheritance and sharedness of structural variants among fathers, mothers, and offsprings. Utilizing single-cell clonal expansion techniques, we observed significant variations in the number of somatic mutations across different tissues. An in-house developed pipeline enabled precise filtering and analysis of these mutations, resulting in the construction of individual phylogenetic trees for two pigs. These trees explored the developmental relationships between different tissues, revealing insights into clonal expansions from various anatomical locations. This study enhances the understanding of pig genomes, affirming their increasing value in clinical and genomic research, and provides a foundation for future studies in other animals, paralleling previous studies in mice and humans. This approach not only deepens our understanding of mammalian genomic variations but also strengthens the role of pigs as a crucial model in human health and disease research.

Development of Novel Surface-Enhanced Raman Spectroscopy-Based Biosensors by Controlling the Roughness of Gold/Alumina Platforms for Highly Sensitive Detection of Pyocyanin Secreted from Pseudomonas aeruginosa.

Pyocyanin is considered a maker of Pseudomonas aeruginosa (P. aeruginosa) infection. Pyocyanin is among the toxins released by the P. aeruginosa bacteria. Therefore, the development of a direct detection of PYO is crucial due to its importance. Among the different optical techniques, the Raman technique showed unique advantages because of its fingerprint data, no sample preparation, and high sensitivity besides its ease of use. Noble metal nanostructures were used to improve the Raman response based on the surface-enhanced Raman scattering (SERS) technique. Anodic metal oxide attracts much interest due to its unique morphology and applications. The porous metal structure provides a large surface area that could be used as a hard template for periodic nanostructure array fabrication. Porous shapes and sizes could be controlled by controlling the anodization parameters, including the anodization voltage, current, temperature, and time, besides the metal purity and the electrolyte type/concentration. The anodization of aluminum foil results in anodic aluminum oxide (AAO) formation with different roughness. Here, we will use the roughness as hotspot centers to enhance the Raman signals. Firstly, a thin film of gold was deposited to develop gold/alumina (Au/AAO) platforms and then applied as SERS-active surfaces. The morphology and roughness of the developed substrates were investigated using scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques. The Au/AAO substrates were used for monitoring pyocyanin secreted from Pseudomonas aeruginosa microorganisms based on the SERS technique. The results showed that the roughness degree affects the enhancement efficiency of this sensor. The high enhancement was obtained in the case of depositing a 30 nm layer of gold onto the second anodized substrates. The developed sensor showed high sensitivity toward pyocyanin with a limit of detection of 96 nM with a linear response over a dynamic range from 1 µM to 9 µM.

Drug Evaluation of Parkinson's Disease Patient-Derived Midbrain Organoids Using Mesoporous Au Nanodot-Patterned 3D Concave Electrode.

Brain organoids are being recognized as valuable tools for drug evaluation in neurodegenerative diseases due to their similarity to the human brain's structure and function. However, a critical challenge is the lack of selective and sensitive electrochemical sensing platforms to detect the response of brain organoids, particularly changes in the neurotransmitter concentration upon drug treatment. This study introduces a 3D concave electrode patterned with a mesoporous Au nanodot for the detection of electrochemical signals of dopamine in response to drugs in brain organoids for the first time. The mesoporous Au nanodot-patterned film was fabricated using laser interference lithography and electrochemical deposition. Then, the film was attached to a polymer-based 3D concave mold to obtain a 3D concave electrode. Midbrain organoids generated from Parkinson's disease (PD) patient-derived iPSCs with gene mutations (named as PD midbrain organoid) or normal midbrain organoids were positioned on the developed 3D concave electrode. The 3D concave electrode showed a 1.4 times higher electrochemical signal of dopamine compared to the bare gold electrode. And the dopamine secreted from normal midbrain organoids or PD midbrain organoids on the 3D concave electrode could be detected electrochemically. After the treatment of PD midbrain organoids with levodopa, the drug for PD, the increase in dopamine level was detected due to the activation of dopaminergic neurons by the drug. The results suggest the potential of the proposed 3D concave electrode combined with brain organoids as a useful tool for assessing drug efficacy. This sensing system can be applied to a variety of organoids for a comprehensive drug evaluation.

Green Synthesized Chitosan Nanoparticles for Controlling Multidrug-Resistant mecA- and blaZ-Positive Staphylococcus aureus and aadA1-Positive Escherichia coli.

Antimicrobial resistance has recently been considered an emerging catastrophe globally. The public health and environmental threats were aggravated by the injudicious use of antibiotics in animal farming, aquaculture, and croup fields, etc. Consequently, failure of antibiotic therapies is common because of the emergence of multidrug-resistant (MDR) bacteria in the environment. Thus, the reduction in antibiotic spillage in the environment could be an important step for overcoming this situation. Bear in mind, this research was focused on the green synthesis of chitosan nanoparticles (ChiNPs) using Citrus lemon (Assam lemon) extract as a cross-linker and application in controlling MDR bacteria to reduce the antibiotic spillage in that sector. For evaluating antibacterial activity, Staphylococcus aureus and Escherichia coli were isolated from environmental specimens, and their multidrug-resistant pattern were identified both phenotypically by disk diffusion and genotypically by detecting methicillin- (mecA), penicillin- (blaZ), and streptomycin (aadA1)-resistance encoding genes. The inhibitory zone's diameter was employed as a parameter for determining the antibacterial effect against MDR bacteria revealing 30 ± 0.4 mm, 34 ± 0.2 mm, and 36 ± 0.8 mm zones of inhibition against methicillin- (mecA) and penicillin (blaZ)-resistant S. aureus, and streptomycin (aadA1)-resistant E. coli, respectively. The minimum inhibitory concentration at 0.31 mg/mL and minimum bactericidal concentration at 0.62 mg/mL of yielded ChiNPs were used as the broad-spectrum application against MDR bacteria. Finally, the biocompatibility of ChiNPs was confirmed by showing a negligible decrease in BHK-21 cell viability at doses less than 2 MIC, suggesting their potential for future application in antibiotic-free farming practices.

An antioxidant and anti-ER stress combination therapy elevates phosphorylation of α-Syn at serine 129 and alleviates post-TBI PD-like pathology in a sex-specific manner in mice.

Clinical studies have shown that traumatic brain injury (TBI) increases the onset of Parkinson's disease (PD) in later life by >50%. Oxidative stress, endoplasmic reticulum (ER) stress, and inflammation are the major drivers of both TBI and PD pathologies. We presently evaluated if curtailing oxidative stress and ER stress concomitantly using a combination of apocynin and tert-butylhydroquinone and salubrinal during the acute stage after TBI in mice reduces the severity of late-onset PD-like pathology. The effect of multiple low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on post-TBI neurodegeneration was also evaluated. The combo therapy elevated the level of phosphorylation at serine 129 (pS129) of α-Syn in the pericontusional cortex of male mice at 72 h post-TBI. Motor and cognitive deficits induced by TBI lasted at least 3 months and the combo therapy curtailed these deficits in both sexes. At 3 months post-TBI, male mice given combo therapy exhibited significantly lesser α-Syn aggregates in the SN and higher TH+ cells in the SNpc, compared to vehicle control. However, the aggregate number was not significantly different between groups of female mice. Moreover, TBI-induced loss of TH+ cells was negligible in female mice irrespective of treatment. The MPTP treatment aggravated PD-like pathology in male mice but had a negligible effect on the loss of TH+ cells in female mice. Thus, the present study indicates that mitigation of TBI-induced oxidative stress and ER stress at the acute stage could potentially reduce the risk of post-TBI PD-like pathology at least in male mice, plausibly by elevating pS129-α-Syn level.

Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome.

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates. Herein, the study presents a Magnetic Nanoparticle-Assisted Genome Editing (MAGE) platform, which significantly improves the transfection efficiency, biocompatibility, and genome-editing accuracy of CRISPR-Cas9 technology. To demonstrate the feasibility of the developed technology, MAGE is applied to correct the mutated MeCP2 gene in induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) from a Rett syndrome patient. By combining magnetofection and magnetic-activated cell sorting, MAGE achieves higher multi-plasmid delivery (99.3%) and repairing efficiencies (42.95%) with significantly shorter incubation times than conventional transfection agents without size limitations on plasmids. The repaired iPSC-NPCs showed similar characteristics as wild-type neurons when they differentiated into neurons, further validating MAGE and its potential for future clinical applications. In short, the developed nanobio-combined CRISPR-Cas9 technology offers the potential for various clinical applications, particularly in stem cell therapies targeting different genetic diseases.

Carbon-based nanocomposites for biomedical applications.

Carbon nanomaterials have attracted significant attention in the biomedical field, including for biosensing, drug delivery, and tissue engineering applications. Based on their inherent properties such as their unique structure and high conductivity, carbon nanomaterials can overcome the current limitations in biomedical research such as poor stability of biomolecules, low sensitivity and selectivity of biosensors, and difficulty in precise drug delivery. In addition, recently, several novel nanomaterials have been integrated with carbon nanomaterials to develop carbon-based nanocomposites for application in biomedical research. In this review, we discuss recent studies on carbon-based nanocomposites and their biomedical applications. First, we discuss the representative carbon nanomaterials and nanocomposites composed of carbon and other novel nanomaterials. Next, applications of carbon nanomaterials and nanocomposites in the biomedical field are discussed according to topics in the biomedical field. We have discussed the recent studies on biosensors, drug delivery, and tissue engineering. In conclusion, we believe that this review provides the potential and applicability of carbon nanomaterials and their nanocomposites and suggests future directions of the application of carbon-based nanocomposites in biomedical applications.

Human Motor System-Based Biohybrid Robot-On-a-Chip for Drug Evaluation of Neurodegenerative Disease.

Biohybrid robots have been developed for biomedical applications and industrial robotics. However, the biohybrid robots have limitations to be applied in neurodegenerative disease research due to the absence of a central nervous system. In addition, the organoids-on-a-chip has not yet been able to replicate the physiological function of muscle movement in the human motor system, which is essential for evaluating the accuracy of the drugs used for treating neurodegenerative diseases. Here, a human motor system-based biohybrid robot-on-a-chip composed of a brain organoid, multi-motor neuron spheroids, and muscle bundle on solid substrateis proposed to evaluate the drug effect on neurodegenerative diseases for the first time. The electrophysiological signals from the cerebral organoid induced the muscle bundle movement through motor neuron spheroids. To evaluate the drug effect on Parkinson's disease (PD), a patient-derived midbrain organoid is generated and incorporated into a biohybrid robot-on-a-chip. The drug effect on PD is successfully evaluated by measuring muscle bundle movement. The muscle bundle movement of PD patient-derived midbrain organoid-based biohybrid robot-on-a-chip is increased from 4.5 ± 0.99 µm to 18.67 ± 2.25 µm in response to levodopa. The proposed human motor system-based biohybrid robot-on-a-chip can serve as a standard biohybrid robot model for drug evaluation.

Facile synthesis of CuONPs using Citrus limon juice for enhancing antibacterial activity against methicillin-resistant Staphylococcus aureus, beta-lactamase and tetracycline-resistant Escherichia coli.

Antimicrobial resistance (AMR) resulting from indiscriminate use of antibiotics in various fields of agriculture such as livestock farming, aquaculture, and croup fields become an emerging catatroph for the health (human, animal) and environment. Among those, poultry farming has been considered as one of the major contributors of multidrug-resistant (MDR) bacteria. Focusing this, the present research is designed for green synthesis of copper oxide nanoparticles (CuONPs) with the aim of their application in antibiotic-free poultry farming for curving use of antibiotics in that sector. For that, antibacterial CuONPs were nanoformulated to decrease the required doses of bulk CuSO4. We used a CuSO4·5H2O solution as a Cu2+ source and Citrus limon juice as a reducing agent as well as capping agent. Particle yield was initially confirmed by the λmax specific to CuONPs (295 nm) using UV-Vis spectroscopy. The presence of the Cu-O group during particle formation and crystallinity with the purity of yielded NPs was confirmed with Fourier-transform infrared spectroscopy and X-ray diffractometry. The round to spherical CuONPs of 92-155 nm average size was confirmed with atomic force, scanning electron, and transmission electron microscopy. The concentration of yielded NPs was calculated with the dynamic light scattering. The physical characterization tools indicated a maximum CuONPs yield with a 0.001 M ion source with 15% reducing agents after 12 h reduction. Antibacterial effectivity was tested against methicillin-resistant Staphylococcus aureus and tetracycline- and beta-lactamase-resistant Escherichia coli, confirmed by PCR amplicon band at 163 bp, 643 bp, and 577 bp for the mecA, blaTEM-1 and tetA genes, respectively. An antibiogram assay of CuONPs showed a maximum zone of inhibition of 26 ± 0.5 mm for the synthesized particles. The minimum inhibitory and bactericidal concentrations were 1.6 µg ml-1 and 3.1 µg ml-1, respectively, for broad-spectrum application. Finally, the biocompatibility of CuONPs was determined by demonstrating a nonsignificant decrease of BHK-21 cell viability at <2 MIC doses for complying their future in vivo applicability.

Recombinant protein embedded liposome on gold nanoparticle based on LSPR method to detect Corona virus.

Antibody sensor to detect viruses has been widely used but has problems such as the difficulty of right direction control of the receptor site on solid substrate, and long time and high cost for design and production of antibodies to new emerging viruses. The virus detection sensor with a recombinant protein embedded liposome (R/Li) was newly developed to solve the above problems, in which R/Li was assembled on AuNPs (Au@R/Li) to increase the sensitivity using localized surface plasmon resonance (LSPR) method. Recombinant angiotensin-converting enzyme-2 (ACE2) was used as host receptors of SARS-CoV and SARS-CoV-2, and the direction of enzyme active site for virus attachment could be controlled by the integration with liposome. The recombinant protein embedded liposomes were assembled on AuNPs, and LSPR method was used for detection. With the sensor platform S1 protein of both viruses was detected with detection limit of 10 pg/ml and SARS-CoV-2 in clinical samples was detected with 10 ~ 35 Ct values. In the selectivity test, MERS-CoV did not show a signal due to no binding with Au@R/Li. The proposed sensor platform can be used as promising detection method with high sensitivity and selectivity for the early and simple diagnosis of new emerging viruses.

Nano-Enabled Antivirals for Overcoming Antibody Escaped Mutations Based SARS-CoV-2 Waves.

This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology and the development of antiviral nanomaterials with physical antagonistic features of viral replication checkpoints as such a solution. Our detailed discussion of SARS-CoV-2 replication and pathogenesis highlights four distinct checkpoints, the S protein (ACE2 receptor coupling), the RBD motif (ACE2 receptor coupling), ACE2 coupling, and the S protein cleavage site, as targets for the development of nano-enabled solutions that, for example, prevent viral attachment and fusion with the host cell by either blocking viral RBD/spike proteins or cellular ACE2 receptors. As proof of this concept, we highlight applications of several nanomaterials, such as metal and metal oxide nanoparticles, carbon-based nanoparticles, carbon nanotubes, fullerene, carbon dots, quantum dots, polymeric nanoparticles, lipid-based, polymer-based, lipid-polymer hybrid-based, surface-modified nanoparticles that have already been employed to control viral infections. These nanoparticles were developed to inhibit receptor-mediated host-virus attachments and cell fusion, the uncoating of the virus, viral gene expression, protein synthesis, the assembly of progeny viral particles, and the release of the virion. Moreover, nanomaterials have been used as antiviral drug carriers and vaccines, and nano-enabled sensors have already been shown to enable fast, sensitive, and label-free real-time diagnosis of viral infections. Nano-biosensors could, therefore, also be useful in the remote testing and tracking of patients, while nanocarriers probed with target tissue could facilitate the targeted delivery of antiviral drugs to infected cells, tissues, organs, or systems while avoiding unwanted exposure of non-target tissues. Antiviral nanoparticles can also be applied to sanitizers, clothing, facemasks, and other personal protective equipment to minimize horizontal spread. We believe that the nanotechnology-enabled solutions described in this review will enable us to control repeated SAR-CoV-2 waves caused by antibody escape mutations.

A Nano-Biohybrid-Based Bio-Solar Cell to Regulate the Electrical Signal Transmission to Living Cells for Biomedical Application.

Bio-solar cells are studied as sustainable and biocompatible energy sources with significant potential for biomedical applications. However, they are composed of light-harvesting biomolecules with narrow absorption wavelengths and weak transient photocurrent generation. In this study, a nano-biohybrid-based bio-solar cell composed of bacteriorhodopsin, chlorophyllin, and Ni/TiO2 nanoparticles is developed to overcome the current limitations and verify the possibility of biomedical applications. Bacteriorhodopsin and chlorophyllin are introduced as light-harvesting biomolecules to broaden the absorption wavelength. As a photocatalyst, Ni/TiO2 nanoparticles are introduced to generate a photocurrent and amplify the photocurrent generated by the biomolecules. The developed bio-solar cell absorbs a broad range of visible wavelengths and generates an amplified stationary photocurrent density (152.6 nA cm-2 ) with a long lifetime (up to 1 month). Besides, the electrophysiological signals of muscle cells at neuromuscular junctions are precisely regulated by motor neurons excited by the photocurrent of the bio-solar cell, indicating that the bio-solar cell can control living cells by signal transmission through other types of living cells. The proposed nano-biohybrid-based bio-solar cell can be used as a sustainable and biocompatible energy source for the development of wearable and implantable biodevices and bioelectronic medicines for humans.

Nanomaterial-based biohybrid hydrogel in bioelectronics.

Despite the broadly applicable potential in the bioelectronics, organic/inorganic material-based bioelectronics have some limitations such as hard stiffness and low biocompatibility. To overcome these limitations, hydrogels capable of bridging the interface and connecting biological materials and electronics have been investigated for development of hydrogel bioelectronics. Although hydrogel bioelectronics have shown unique properties including flexibility and biocompatibility, there are still limitations in developing novel hydrogel bioelectronics using only hydrogels such as their low electrical conductivity and structural stability. As an alternative solution to address these issues, studies on the development of biohybrid hydrogels that incorporating nanomaterials into the hydrogels have been conducted for bioelectronic applications. Nanomaterials complement the shortcomings of hydrogels for bioelectronic applications, and provide new functionality in biohybrid hydrogel bioelectronics. In this review, we provide the recent studies on biohybrid hydrogels and their bioelectronic applications. Firstly, representative nanomaterials and hydrogels constituting biohybrid hydrogels are provided, and next, applications of biohybrid hydrogels in bioelectronics categorized in flexible/wearable bioelectronic devices, tissue engineering, and biorobotics are discussed with recent studies. In conclusion, we strongly believe that this review provides the latest knowledge and strategies on hydrogel bioelectronics through the combination of nanomaterials and hydrogels, and direction of future hydrogel bioelectronics.

A photoluminescence sensor for in-situ monitoring of the dopamine neurotransmitters released from PC12 cells.

Constructing simple, stable, fast, and sensitive neurotransmitter-based sensors is a promising tool to diagnose neurological diseases. Dopamine (DA), "a catecholamine neurotransmitter" is important in transmitting nerve impulses. Therefore, great attention is taken to monitor DA concentrations received. The challenge in developing a DA-based sensor is to enhance its stability and sensitivity. Thus, we have used o-phthalaldehyde (OPA)/2-mercapto ethanol (2ME)/mesoporous silica instated of 2ME in solution. Here we have successfully developed a fluorescence DA neurotransmitters sensor. The sensor was used for detecting a wide range of concentrations of DA (5 nM to 5 µM). Effects of pH (4.3-11.4) and temperatures (25-70 °C) on the sensor efficiency were investigated. The detection limit was 1.35 × 10-11 mol/dm3, which is lower than the normal DA level in the central nervous system. The results indicated that using OPA/2ME/MSNPs has long-time stability over a year of its preparation. Moreover, the developed sensor showed high specificity towards DA in the presence of different interferences such as ascorbic acid or another catecholamine neurotransmitter such as γ-aminobutyric acid. Finally, the fabricated biosensor was used to monitor the DA neurotransmitter released from PC12 cells. Hence, it was successfully developed a simple and stable probe for accurate photoluminescence detection of DA neurotransmitters.

International Normalized Ratio-to-Albumin Ratio as a Novel Marker of Upper Gastrointestinal Bleeding Severity.

Introduction: Upper gastrointestinal bleeding (UGIB) is a potentially life-threatening gastrointestinal emergency, and effective management depends on early risk stratification. The Glasgow-Blatchford and Rockall scores are commonly used prognostic measures for UGIB, although these scoring systems are relatively difficult to apply in early emergency settings. AIMS65 with five items, albumin, international normalized ratio, mental status, systolic blood pressure, and age (>65 years), showed efficacy in predicting long-term hospitalization and mortality. This study aimed to investigate the usefulness of the prothrombin time-international normalized ratio-to-albumin ratio (PTAR) in the emergency room for early UGIB risk stratification. Methods: We retrospectively examined patients who visited a tertiary academic hospital's emergency department (ED) with UGIB as the chief presentation between January 2019 and December 2020. The cutoff values and diagnostic accuracies of the PTAR, Glasgow-Blatchford score, AIMS65 score, pre-endoscopy, and complete Rockall score were analyzed, and the performance of the PTAR was compared with that of other risk stratification methods. In total, 519 patients were enrolled: 163 patients were admitted in the intensive care unit (ICU) and 35 died during admission. Multiple logistic regression analyses confirmed the association of the PTAR with ICU admission and mortality. The adjusted odd ratio (aOR) of the PTAR for ICU admission care was 8.376 (2.722-25.774), and the aOR of the PTAR for mortality was 27.846 (8.701-89.116). Conclusions: The PTAR measured in the ED is an independent factor related to ICU admission and mortality in patients with UGIB. Using ED blood laboratory results, which are reported relatively quickly and are easy to acquire and calculate, the PTAR can be used as a risk stratification marker in the early emergency setting.

An antioxidant and anti-ER stress combo therapy decreases inflammation, secondary brain damage and promotes neurological recovery following traumatic brain injury in mice.

The complex pathophysiology of post-traumatic brain damage might need a polypharmacological strategy with a combination of drugs that target multiple, synergistic mechanisms. We currently tested a combination of apocynin (curtails formation of reactive oxygen species; ROS), tert-butylhydroquinone (promotes disposal of ROS), and salubrinal (prevents endoplasmic reticulum stress) following a moderate traumatic brain injury (TBI) induced by controlled cortical impact in adult mice. Adult mice of both sexes treated with the above tri-combo showed alleviated motor and cognitive deficits, attenuated secondary lesion volume, and decreased oxidative DNA damage. Concomitantly, tri-combo treatment regulated post-TBI inflammatory response by decreasing the infiltration of T cells and neutrophils and activation of microglia in both sexes. Interestingly, sexual dimorphism was seen in the case of TBI-induced microgliosis and infiltration of macrophages in the tri-combo treated mice. Moreover, the tri-combo treatment prevented TBI-induced white matter volume loss in both sexes. The beneficial effects of tri-combo treatment were long-lasting and were also seen in aged mice. Thus, the present study supports the tri-combo treatment to curtail oxidative stress and endoplasmic reticulum stress concomitantly as a therapeutic strategy to improve TBI outcomes.SIGNIFICANCE STATEMENTOf the several mechanisms that contribute to TBI pathophysiology, oxidative stress, endoplasmic reticulum (ER) stress, and inflammation play a major role. The present study shows the therapeutic potential of a combination of apocynin, tert-butylhydroquinone, and salubrinal to prevent oxidative stress and ER stress and the interrelated inflammatory response in mice subjected to TBI. The beneficial effects of the tri-combo include alleviation of TBI-induced motor and cognitive deficits and lesion volume. The neuroprotective effects of the tri-combo are also linked to its ability to prevent TBI-induced white matter damage. Importantly, neuroprotection by the tri-combo treatment was observed to be not dependent on sex or age. Our data demonstrate that a polypharmacological strategy is efficacious after TBI.

Recent progress in nanomaterial-based bioelectronic devices for biocomputing system.

Bioelectronic devices have received the massive attention because of their huge potential to develop the core electronic components for biocomputing system. Up to now, numerous bioelectronic devices have been reported such as biomemory and biologic gate by employment of biomolecules including metalloproteins and nucleic acids. However, the intrinsic limitations of biomolecules such as instability and low signal production hinder the development of novel bioelectronic devices capable of performing various novel computing functions. As a way to overcome these limitations, nanomaterials have the great potential and wide applicability to grant and extend the electronic functions, and improve the inherent properties from biomolecules. Accordingly, lots of nanomaterials including the conductive metal, graphene, and transition metal dichalcogenide nanomaterials are being used to develop the remarkable functional bioelectronic devices like the multi-bit biomemory and resistive random-access biomemory. This review discusses the nanomaterial-based superb bioelectronic devices including the biomemory, biologic gates, and bioprocessors. In conclusion, this review will provide the interdisciplinary information about utilization of various novel nanomaterials applicable for biocomputing system.