Hydrogel-Gated FETs in Neuromorphic Computing to Mimic Biological Signal: A Review.

Hydrogel-gated synaptic transistors offer unique advantages, including biocompatibility, tunable electrical properties, being biodegradable, and having an ability to mimic biological synaptic plasticity. For processing massive data with ultralow power consumption due to high parallelism and human brain-like processing abilities, synaptic transistors have been widely considered for replacing von Neumann architecture-based traditional computers due to the parting of memory and control units. The crucial components mimic the complex biological signal, synaptic, and sensing systems. Hydrogel, as a gate dielectric, is the key factor for ionotropic devices owing to the excellent stability, ultra-high linearity, and extremely low operating voltage of the biodegradable and biocompatible polymers. Moreover, hydrogel exhibits ionotronic functions through a hybrid circuit of mobile ions and mobile electrons that can easily interface between machines and humans. To determine the high-efficiency neuromorphic chips, the development of synaptic devices based on organic field effect transistors (OFETs) with ultra-low power dissipation and very large-scale integration, including bio-friendly devices, is needed. This review highlights the latest advancements in neuromorphic computing by exploring synaptic transistor developments. Here, we focus on hydrogel-based ionic-gated three-terminal (3T) synaptic devices, their essential components, and their working principle, and summarize the essential neurodegenerative applications published recently. In addition, because hydrogel-gated FETs are the crucial members of neuromorphic devices in terms of cutting-edge synaptic progress and performances, the review will also summarize the biodegradable and biocompatible polymers with which such devices can be implemented. It is expected that neuromorphic devices might provide potential solutions for the future generation of interactive sensation, memory, and computation to facilitate the development of multimodal, large-scale, ultralow-power intelligent systems.

T Cell Responses in Pregnant Women Who Received mRNA-Based Vaccination to Prevent COVID-19 Revealed Unknown Exposure to the Natural Infection and Numerous SARS-CoV-2-Specific CD4- CD8- Double Negative T Cells and Regulatory T Cells.

We studied T-cell responses to SARS-CoV-2 in 19 pregnant subjects at different gestational weeks who received three doses of mRNA-based vaccination to prevent COVID-19. SARS-CoV-2 peptide pools were used for T-cell recognition studies: peptides were 15 amino acids long and had previously been defined in COVID-19-convalescent subjects. T-cell activation was evaluated with the AIM assay. Most subjects showed coordinated, spike-specific CD4+ and CD8+ T-cell responses and the development of T cell memory. Non-spike-specific T cells in subjects who were not aware of previous COVID-19 infection suggested a prior undetected, asymptomatic infection. CD4- CD8- double negative (DN) T cells were numerous, of which a percentage was specific for SARS-CoV-2 spike peptides. Regulatory T cells (Treg), both spike- and non-spike-specific, were also greatly expanded. Two Treg populations were defined: a population differentiated from naïve T cells, and pTreg, reverting from pro-inflammatory T cells. The Treg cells expressed CCR6, suggesting homing to the endometrium and vaginal epithelial cells. The pregnant women responded to SARS-CoV-2 vaccination. Asymptomatic COVID-19 was revealed by the T cell response to the non-spike peptides. The numerous DN T cells and Treg pointed our attention to new aspects of the adaptive immune response in vaccine recipients.

Dielectrophoretic force-induced wrinkling of graphene oxide: Enhancing electrical conductivity and expanding biosensing applications.

Graphene oxide (GO) has many advantages, making it suitable for various applications. However, it has low electrical conductivity, restricting its applicability to electrochemical biosensors. This study used dielectrophoretic (DEP) force to control the movement and deformation of GO nanosheets to achieve high electrical conductivity without the chemical reduction of oxygen functional groups. Subjecting the DEP force to GO nanosheets induced physical deformation leading to the formation of wrinkled structures. A computational simulation was performed to set an appropriate electrical condition for operating a positive DEP force effect of at least 1019 v2/m3, and the interdigitated microelectrode structure was selected. The resulting wrinkled GO exhibited significantly improved electrical conductivity, reaching 21.721 µS while preserving the essential oxygen functional groups. Furthermore, a biosensor was fabricated using wrinkled GO deposited via DEP force. The biosensor demonstrated superior sensitivity, exhibiting a 9.6-fold enhancement compared with reduced GO (rGO) biosensors, as demonstrated through biological experiments targeting inducible nitric oxide synthase. This study highlights the potential of using DEP force to enhance electrical conductivity in GO-based biosensing applications, opening new avenues for high-performance diagnostics.

SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19.

We enrolled healthy subjects that received 2 to 4 injections of mRNA-based vaccination to prevent COVID-19 months to a year from the last vaccine boost, and we found numerous SARS-CoV-2 spike-specific regulatory T cell (Treg) that developed T cell memory as effector memory T cells (TEM) and central memory T cells (TCM). CD4+ CD25high Treg expressed the chemokine receptor CCR6 in a considerable percentage, suggesting T cell homing to the vascular endothelium, lung and gut epithelial cells and brain. Treg phenotype was different than peripherally-induced Treg (pTreg) that revert from pro-inflammatory T cells under repeated stimulatory conditions, suggesting that SARS-CoV-2 spike-specific Treg differentiated from naïve T cells in tissues where the SARS-CoV-2 spike proteins were synthetized. Twenty two of 22 subjects studied responded to vaccination developing a spike-specific CD4+ T helper (Th)1 response, and 20 of 22 developing a spike-specific CD8+ cytotoxic T cells (CTL) response. However, in vaccine recipients the expansion of spike-specific pro-inflammatory T cells was less significant than the expansion of spike-specific Treg. Effector (TEM) and central memory (TCM) Treg were numerous as early as after two vaccine doses, with no significant differences following additional vaccine boosts. In co-culture experiments under stimulatory conditions, Treg regulated naïve T cell differentiation toward a pro-inflammatory phenotype and suppressed interferon (IFN)γ production by SARS-CoV-2-specific CD4 + Th1 cells.

Recent Advances in Multiplexed Wearable Sensor Platforms for Real-Time Monitoring Lifetime Stress: A Review.

Researchers are interested in measuring mental stress because it is linked to a variety of diseases. Real-time stress monitoring via wearable sensor systems can aid in the prevention of stress-related diseases by allowing stressors to be controlled immediately. Physical tests, such as heart rate or skin conductance, have recently been used to assess stress; however, these methods are easily influenced by daily life activities. As a result, for more accurate stress monitoring, validations requiring two or more stress-related biomarkers are demanded. In this review, the combinations of various types of sensors (hereafter referred to as multiplexed sensor systems) that can be applied to monitor stress are discussed, referring to physical and chemical biomarkers. Multiplexed sensor systems are classified as multiplexed physical sensors, multiplexed physical-chemical sensors, and multiplexed chemical sensors, with the effect of measuring multiple biomarkers and the ability to measure stress being the most important. The working principles of multiplexed sensor systems are subdivided, with advantages in measuring multiple biomarkers. Furthermore, stress-related chemical biomarkers are still limited to cortisol; however, we believe that by developing multiplexed sensor systems, it will be possible to explore new stress-related chemical biomarkers by confirming their correlations to cortisol. As a result, the potential for further development of multiplexed sensor systems, such as the development of wearable electronics for mental health management, is highlighted in this review.

T Cells in Multisystem Inflammatory Syndrome in Children (MIS-C) Have a Predominant CD4+ T Helper Response to SARS-CoV-2 Peptides and Numerous Virus-Specific CD4- CD8- Double-Negative T Cells.

We studied SARS-CoV-2-specific T cell responses in 22 subacute MIS-C children enrolled in 2021 and 2022 using peptide pools derived from SARS-CoV-2 spike or nonspike proteins. CD4+ and CD8+ SARS-CoV-2-specific T cells were detected in 5 subjects, CD4+ T helper (Th) responses alone were detected in 12 subjects, and CD8+ cytotoxic T cell (CTL) responses alone were documented in 1 subject. Notably, a sizeable subpopulation of CD4- CD8- double-negative (DN) T cells out of total CD3+ T cells was observed in MIS-C (median: 14.5%; IQR 8.65-25.3) and recognized SARS-CoV-2 peptides. T cells bearing the Vß21.3 T cell receptor (TcRs), previously reported as pathogenic in the context of MIS-C, were detected in high frequencies, namely, in 2.8% and 3.9% of the CD4+ and CD8+ T cells, respectively. However, Vß21.3 CD8+ T cells that responded to SARS-CoV-2 peptides were detected in only a single subject, suggesting recognition of nonviral antigens in the majority of subjects. Subjects studied 6-14 months after MIS-C showed T cell epitope spreading, meaning the activation of T cells that recognize more SARS-CoV-2 peptides following the initial expansion of T cells that see immunodominant epitopes. For example, subjects that did not recognize nonspike proteins in the subacute phase of MIS-C showed good Th response to nonspike peptides, and/or CD8+ T cell responses not appreciable before arose over time and could be detected in the 6-14 months' follow-up. The magnitude of the Th and CTL responses also increased over time. In summary, patients with MIS-C associated with acute lymphopenia, a classical feature of MIS-C, showed a physiological response to the virus with a prominent role for virus-specific DN T cells.

Intravenous immunoglobulin induces IgG internalization by tolerogenic myeloid dendritic cells that secrete IL-10 and expand Fc-specific regulatory T cells.

Intravenous immunoglobulin (IVIG) is used as an immunomodulatory agent in many inflammatory conditions including Multisystem Inflammatory Syndrome-Children (MIS-C) and Kawasaki disease (KD). However, the exact mechanisms underlying its anti-inflammatory action are incompletely characterized. Here, we show that in KD, a pediatric acute vasculitis that affects the coronary arteries, IVIG induces a repertoire of natural Treg that recognize immunodominant peptides in the Fc heavy chain constant region. To address which antigen-presenting cell (APC) populations present Fc peptides to Treg, we studied the uptake of IgG by innate cells in subacute KD patients 2 weeks after IVIG and in children 1.6-14 years after KD. Healthy adults served as controls. IgG at high concentrations was internalized predominantly by two myeloid dendritic cell (DC) lineages, CD14+ cDC2 and ILT-4+ CD4+ tmDC mostly through Fcγ receptor (R) II and to a lesser extent FcγRIII. Following IgG internalization, these two DC lineages secreted IL-10 and presented processed Fc peptides to Treg. The validation of IVIG function in expanding Fc-specific Treg presented by CD14+ cDC2 and ILT-4+ CD4+ tmDC was addressed in a small cohort of patients with MIS-C. Taken together, these results suggest a novel immune regulatory function of IgG in activating tolerogenic innate cells and expanding Treg, which reveals an important anti-inflammatory mechanism of action of IVIG.

Analysis of ipsilateral and bilateral ratios in male amateur golfers.

The number of injuries that force golfers to quit is also increasing. In particular, the upper body injuries are concerns for amateur golfers. This study was conducted not only to investigate muscular balance, such as ipsilateral and bilateral ratios of the upper body, but to also evaluate the possible problems of muscular joints in amateur golfers. Male golfers (n=10) and a healthy control group (n=10) were recruited for the assessment of muscular function in the upper body, which was measured by an isokinetic dynamometer at 60°/sec. The tested parts were trunk, wrist, forearm, elbow, and shoulder joints. Mann-Whitney U-test was used to evaluate the significance of the differences between groups. The ipsilateral ratios of peak torque or work per repetition (WR) of trunk flexor and extensor in the golfers were not significantly different compared to those of the control group. These results were similar to the shoulder horizontal abductor and adductor. However, there were significant differences in the ipsilateral and bilateral ratios of the wrist, forearm, and elbow joints. Especially, the WR of the wrist flexor, forearm pronator, and elbow flexor on the left side of amateur golfers showed imbalances in bilateral ratios. Moreover, the WR of the wrist and elbow flexors on the left side of amateur golfers were lower than those of the wrist and elbow extensors. Therefore, amateur golfers should strive to prevent injuries of the wrist, forearm, and elbow joints and to reinforce the endurance on those parts of the left side.

Effect of disintegrated sludge recycling on membrane permeability in a membrane bioreactor combined with a turbulent jet flow ozone contactor.

We have combined a turbulent jet flow ozone contactor (TJC) with a membrane bioreactor (MBR) to establish a zero-discharge system in terms of excess sludge in the MBR. The TJC-MBR system was compared with the conventional MBR (Control-MBR) with respect to i) the size and zeta potential of the sludge particles, ii) the loosely bound extra-cellular polymeric substances (EPSs) and tightly bound EPS of the microbial flocs, iii) the porosity and biovolume of the bio-cake accumulated on the membrane, and iv) the membrane permeability. The TJC system generated the ozonated sludge with a negligible amount of loosely bound EPS and a positive zeta potential. As a result, when such ozonated sludge was recycled, the average size of the sludge particles (e.g., microbial flocs) increased in the TJC-MBR. Consequently the bio-cake formed in the TJC-MBR had greater porosity than that in the Control-MBR, giving rise to higher membrane permeability in the TJC-MBR.