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Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored. Methods A prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay. Results Faecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis. Conclusions The findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy.

Abstract Branched-chain amino acids (BCAAs), particularly leucine, are indispensable AAs for immune regulation through metabolic rewiring. However, the molecular mechanism underlying this phenomenon remains unclear. Our investigation revealed that T-cell receptor (TCR)-activated human CD4+ T cells increase the expression of BCAT1, a cytosolic enzyme responsible for BCAA catabolism, and SLC7A5, a major BCAA transporter. This upregulation facilitates increased leucine influx and catabolism, which are particularly crucial for Th17 responses. Activated CD4+ T cells induce an alternative pathway of cytosolic leucine catabolism, generating a pivotal metabolite, β-hydroxy β-methylbutyric acid (HMB), by acting on BCAT1 and 4-hydroxyphenylpyruvate dioxygenase (HPD)/HPD-like protein (HPDL). Inhibition of BCAT1-mediated cytosolic leucine metabolism, either with BCAT1 inhibitor 2 (Bi2) or through BCAT1, HPD, or HPDL silencing using shRNA, attenuates IL-17 production, whereas HMB supplementation abrogates this effect. Mechanistically, HMB contributes to the regulation of the mTORC1-HIF1α pathway, a major signaling pathway for IL-17 production, by increasing the mRNA expression of HIF1α. This finding was corroborated by the observation that treatment with L-β-homoleucine (LβhL), a leucine analog and competitive inhibitor of BCAT1, decreased IL-17 production by TCR-activated CD4+ T cells. In an in vivo experimental autoimmune encephalomyelitis (EAE) model, blockade of BCAT1-mediated leucine catabolism, either through a BCAT1 inhibitor or LβhL treatment, mitigated EAE severity by decreasing HIF1α expression and IL-17 production in spinal cord mononuclear cells. Our findings elucidate the role of BCAT1-mediated cytoplasmic leucine catabolism in modulating IL-17 production via HMB-mediated regulation of mTORC1-HIF1α, providing insights into its relevance to inflammatory conditions.

Although vaccines and antivirals are currently available, influenza virus infections continually present major threats to human health. Due to genetic diversity and variability of influenza viruses, the development of new antiviral agents against the virus remains as a considerable challenge. In this study, we evaluated the antiviral activity of the water extract and ethanol extract of Sorbus commixta Hedl. (SCH), widely used as a medical herb, against influenza A viruses and identified molecular mechanisms for the antiviral activity. The water extract and ethanol extract of SCH demonstrated virucidal activity against influenza A virus at the noncytotoxic concentrations. In addition, cytopathic effect reduction assay and GFP fluorescence image analysis suggest that SCH extracts have inhibitory activity on multiple stages during influenza virus life cycle. Mechanisms studies showed that SCH extracts inhibited the biological functions of influenza viral surface hemagglutinin and neuraminidase proteins that play critical roles in the viral entry and release steps. SCH extracts not only prevented the receptor binding of influenza viral HA to the cellular receptors but also inhibited the HA-mediated membrane fusion. In addition, SCH extracts suppressed the enzyme activity of the viral neuraminidase. The results together suggest that SCH extracts contain antiviral natural compounds that inhibit multiple influenza viral proteins including the viral surface proteins. Our findings suggest that SCH extracts could be promising resources for the development of novel antiviral agents against influenza A viruses.

IntroductionThis study examines the dynamics of public service motivation (PSM), organizational commitment, and perceived innovative culture and their collective influence on innovative behavior in public organizations. It uniquely focuses on intrinsic motivational factors, extends the scope of motivational studies to the public sector, and highlights the crucial role of organizational culture in fostering innovation.MethodsA web-based survey was administered to 1,021 public servants in the central government of the Republic of Korea. Structured questionnaires were used to collect data, and structural equation modeling (SEM) was employed to analyze the relationships between the variables.ResultsThe SEM results confirmed positive correlations between PSM and both organizational commitment and innovative behavior. However, contrary to expectations, organizational commitment did not significantly predict innovative behavior. Additionally, no mediating effect of organizational commitment was observed. Notably, perceived innovative culture was found to moderate the relationship between PSM and organizational commitment, and between organizational commitment and innovative behavior, particularly in environments with a strong innovation focus.DiscussionThese findings underscore the significance of PSM in spurring innovative behavior in the public sector, broadening our understanding of intrinsic motivation. This study also accentuates the influence of organizational culture on these dynamics. In practical terms, this suggests the importance of nurturing individuals with high PSM and fostering an environment that balances perceived innovative culture. While contributing to the fields of organizational psychology and public administration, this study has certain limitations and indicates the need for further research in various contexts.

Abstract Probabilistic computing has been introduced to operate functional networks using a probabilistic bit (p-bit), broadening the computational abilities in non-deterministic polynomial searching operations. However, previous developments have focused on emulating the operation of quantum computers similarly, implementing every p-bit with large weight-sum matrix multiplication blocks and requiring tens of times more p-bits than semiprime bits. In addition, operations based on a conventional simulated annealing scheme required a large number of sampling operations, which deteriorated the performance of the Ising machines. Here we introduce a prime factorization machine with a virtually connected Boltzmann machine and probabilistic annealing method, which are designed to reduce the hardware complexity and number of sampling operations. From 10-bit to 64-bit prime factorizations were performed, and the machine offers up to 1.2 × 108 times improvement in the number of sampling operations compared with previous factorization machines, with a 22-fold smaller hardware resource.

IntroductionThe aging population in South Korea, characterized by an increasing number of older adults living alone, has raised concerns about its implications on mental health, specifically social isolation and loneliness that accompanies solitary living arrangements. This study explores the impact of living arrangements on the mental well-being of Korean older adults by focusing on the prevalence of depression and the role of social isolation in the context of evolving family structures and the COVID-19 pandemic.MethodsThis cross-sectional study analyzed the responses of older adults aged 65 years and above (mean: 73.1, SD: 5.1) by using data from the Korea National Health and Nutrition Examination Survey conducted in 2018 and 2020. In total, responses from 3,365 older adults (1,653 in 2018 and 1,712 in 2020) were employed in this research. The participants’ mental health status was assessed using the Patient Health Questionnaire-9, with living arrangements categorized by household size. A zero-inflated Poisson regression analysis was employed to investigate the relationship between living arrangements and depression severity, controlling for demographic, socioeconomic, and psychological factors.ResultsThe study found that older adults living with others exhibited a lower depression severity than those living alone. Notably, the severity of depression decreased as the number of household members increased up to a certain threshold. Socio-economic factors, such as income level, marital status, and psychological stress were also identified as significant predictors of depression severity. However, the COVID-19 pandemic did not have a statistically significant impact on depression rates among older adults during the study period.ConclusionLiving arrangements play a critical role in the mental health of Korean older adults, with solitary living being associated with higher levels of depression. These findings underscore the importance of social support systems and suggest the need for policies and interventions that promote social connectivity and address the challenges of loneliness faced by them. Future research should explore longitudinal and qualitative studies to further understand causal relationships and develop targeted interventions to improve the mental well-being of the aging population.

This study explores the pedagogical competence of VR-based survival swimming instructors in South Korea, focusing on their application of Technological Pedagogical Content Knowledge (TPACK). Employing qualitative methodology, we conducted in-depth interviews with 11 instructors to understand their instructional strategies within a VR context. The study aimed to identify how instructors integrate TPACK components into their teaching, specifically exploring technological content knowledge (content utilization, equipment preparation, addressing dizziness), pedagogical content knowledge (creating a conducive learning environment, enhancing student engagement), and technological pedagogical knowledge (setting appropriate learning objectives and guidelines, educational assessment), understanding learners, and pedagogical beliefs and philosophy. Our findings reveal that VR-based instructors proficiently blend these knowledge domains to enhance the effectiveness of survival swimming education. The results demonstrate that strategic pedagogical approaches are crucial in leveraging VR technology for educational outcomes, highlighting the importance of instructor competence in successfully implementing VR in teaching. This research contributes to the literature by detailing specific competencies critical for VR-based education and suggesting that a thorough understanding and application of the TPACK framework are essential for optimizing VR’s educational potential.

IntroductionThe Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic infectious virus that has caused significant outbreaks in the Middle East and beyond. Due to a highly mortality rate, easy transmission, and rapid spread of the MERS-CoV, it remains as a significant public health treat. There is currently no licensed vaccine available to protect against MERS-CoV.MethodsIn this study, we investigated whether the proteolytic cleavage sites and fusion peptide domain of the MERS-CoV spike (S) protein could be a vaccine target to elicit the MERS-CoV S protein-specific antibody responses and confer immune protection against MERS-CoV infection. Our results demonstrate that immunization of the proteolytic cleavage sites and the fusion peptide domain using virus-like particle (VLP) induced the MERS-CoV S protein-specific IgG antibodies with capacity to neutralize pseudotyped MERS-CoV infection in vitro. Moreover, proteolytic cleavage sites and the fusion peptide VLP immunization showed a synergistic effect on the immune protection against MERS-CoV infection elicited by immunization with VLP expressing the receptor binding domain (RBD) of the S protein. Additionally, immune evasion of MERS-CoV RBD variants from anti-RBD sera was significantly controlled by anti-proteolytic cleavage sites and the fusion peptide sera.Conclusion and discussionOur study demonstrates the potential of VLP immunization targeting the proteolytic cleavage sites and the fusion peptide and RBD domains of the MERS-CoV S protein for the development of effective treatments and vaccines against MERS-CoV and related variants.

Abstract A 4.5 Gb/s/pin transceiver capable of eliminating the inter‐symbol interference (ISI) and far‐end crosstalk (FEXT) in a hybrid scheme with low power and small area for next‐generation high‐bandwidth memory (HBM) interfaces is presented. Built around the combination of two ISI and FEXT equalization topologies, the transmitter (TX) energy efficiently reduces data‐dependent jitter (DDJ) and crosstalk‐induced jitter (CIJ) by using the compensation signal generated from edge detectors (ED) to ensure the sampling margin. The prototype transceiver, implemented using a 28‐nm complementary metal‐oxide semiconductor (CMOS) process, operates over a 3‐mm mimicked silicon interposer channel with 21.2‐dB loss. It achieves a data rate per density of 9 Gb/s/μm at a bit error rate (BER) < 10–12 with 0.23 unit interval (UI) eye width for pseudorandom binary sequence (PRBS)15 data while consuming only 1.46 pJ/bit.

Abstract MicroRNAs (miRNAs) are regulatory noncoding RNAs important for many aspects of cellular processes including cell differentiation and proliferation. Functions of numerous miRNAs have been identified in T cells, with miR-181a regulating T cell activation thresholds during thymic T cell development and during activation of peripheral T cells. Intriguingly, miR-181a is implicated in defective antiviral and vaccine responses in older individuals, as its expression declines in naïve T cells with increasing age. Here, we review the pathways that are regulated by miR-181a and that explain the unique role of miR-181a in T cell development, T cell activation and antiviral T cell responses. These studies provide a framework for understanding how a decline in miR-181a expression in T cells could contribute to age-related defects in adaptive immunity. We furthermore review the mechanisms that cause the age-related decline in miR-181a expression and discuss the potential of restoring miR-181a expression or targeting miR-181a-regulated pathways to improve impaired T cell responses in older individuals.

This study examined the impact of superiors’ ethical leadership on subordinates’ unethical pro-organizational behavior (UPB) and the mediating effects of followership. The research subjects were officials from the ten central departments of the South Korean government, and a cross-sectional survey was conducted among them. Overall, 404 questionnaires were used in the empirical analysis. Multiple regression analysis and Hayes Process Macro were used to validate the research hypotheses, which examined the relationship among ethical leadership, followership, and UPB. The results are as follows: First, the relationship between ethical leadership and followership was statistically significant. Second, the study showed that followership had a statistically significant effect on UPB but not ethical leadership. Third, testing the hypotheses regarding the mediating effect of followership on the relationship between ethical leadership and UPB revealed statistically significant results. This study confirms that followership significantly influences UPB and suggests that ethical leadership is an important precedent factor of followership. The study concludes with the theoretical and practical implications of these findings, along with the study’s limitations.

This paper presents an area- and energy- efficient digital sub-sampling clock and data recovery (CDR) with combined adaptive equalizer and self-error corrector (SEC). Using the digitized phase difference between the incoming data and the full-rate output clock of a digitally controlled oscillator (DCO) for both the equalizer adaptation and clock recovery loop, the proposed adaptive equalizer is combined with the CDR by sharing its adaptation loop including a sub-sampling phase detector (SSPD) and a digital logic circuit. Consequently, the active area and power dissipation for the adaptive equalizer are reduced. Furthermore, the SEC is proposed to improve the high-frequency jitter tolerance of the CDR. The SEC detects bit errors by observing the comparator decision and corrects the errors without any data encoding or complicate circuits. The out-of-band jitter tolerance is improved by 22.6% at 100 MHz for 17.2-dB loss channel with −12 bit-error rate (BER) with the proposed SEC. The SEC is applicable to various receivers with compact design at a low cost. The prototype receiver consumes 23.9 mW at 14-Gb/s and occupies 0.007 mm2 in a 28-nm CMOS technology.

MicroRNA miR-181a has been implicated in the regulation of T cell activation and development. Here the authors show that miR-181a is regulated by a transcription factor, YY1, with reduced YY1 expression linked to reduced miR-181a in old individuals, while silencing YY1 impairs T cell functions largely through influencing the expression of miR-181a targets.

Summary: Generation of protective immunity to infections and vaccinations declines with age. Studies in healthy individuals have implicated reduced miR-181a expression in T cells as contributing to this defect. To understand the impact of miR-181a expression on antiviral responses, we examined LCMV infection in mice with miR-181ab1-deficient T cells. We found that miR-181a deficiency delays viral clearance, thereby biasing the immune response in favor of CD4 over CD8 T cells. Antigen-specific CD4 T cells in mice with miR-181a-deficient T cells expand more and have a broader TCR repertoire with preferential expansion of high-affinity T cells than in wild-type mice. Importantly, generation of antigen-specific miR-181a-deficient CD8 effector T cells is particularly impaired, resulting in lower frequencies of CD8 T cells in the liver even at time points when the infection has been cleared. Consistent with the mouse model, CD4 memory T cells in individuals infected with West Nile virus at older ages tend to be more frequent and of higher affinity. : T cell aging in humans is associated with progressive loss in miR-181a, the implications of which for antiviral immunity are unknown. Using mouse models, Kim et al. find that miR-181a deficiency in T cells reproduces many aging features including impaired effector T cell expansion, viral clearance, generation of tissue-residing T cells, and recall responses. Keywords: immunosenescence, antiviral response, microRNA, CD8 effector T cell, T cell repertoire, immune aging

Summary: Induction of protective vaccine responses, governed by the successful generation of antigen-specific antibodies and long-lived memory T cells, is increasingly impaired with age. Regulation of the T cell proteome by a dynamic network of microRNAs is crucial to T cell responses. Here, we show that activation-induced upregulation of miR-21 biases the transcriptome of differentiating T cells away from memory T cells and toward inflammatory effector T cells. Such a transcriptome bias is also characteristic of T cell responses in older individuals who have increased miR-21 expression and is reversed by antagonizing miR-21. miR-21 targets negative feedback circuits in several signaling pathways. The concerted, sustained activity of these signaling pathways in miR-21high T cells disfavors the induction of transcription factor networks involved in memory cell differentiation. Our data suggest that curbing miR-21 upregulation or activity in older individuals may improve their ability to mount effective vaccine responses. : A hallmark of the aging immune system is its failure to induce long-lived memory. Kim et al. report that increased expression of miR-21 in naive T cells from older individuals sustains signaling in the MAPK and AKT-mTORC pathways, disfavoring induction of transcription factor networks involved in memory cell generation. Keywords: T memory cell, short-lived T effector cell, T cell differentiation, immune aging, immunosenescence, vaccination, microRNA

The complete chloroplast genome sequence of Castanea crenata was sequenced and assembled using PacBio Sequel data. The cpDNA was 160,787 bp in length, containing a pair of inverted repeats (IRs) of 25,654 bp each separated by a large and small single copy (LSC and SSC) regions of 90,645 bp and 18,836 bp, respectively. The cpDNA contained 102 genes, including 65 protein-coding genes, 8 ribosomal RNA genes and 37 transfer RNA genes. Phylogenetic analysis indicated that C. crenata was closest to C. pumila var. pumila, which is known as a typical variety of American chinquapin or dwarf chestnut.

The parameters that modulate the functional capacity of secondary Th1 effector cells are poorly understood. In this study, we employ a serial adoptive transfer model system to show that the functional differentiation and secondary memory potential of secondary CD4+ effector T cells are dependent on the inflammatory environment of the secondary challenge. Adoptive transfer of TCR transgenic lymphocytic choriomeningitis virus (LCMV) Glycoprotein-specific SMARTA memory cells into LCMV-immune hosts, followed by secondary challenge with Listeria monocytogenes recombinantly expressing a portion of the LCMV Glycoprotein (Lm-gp61), resulted in the rapid emergence of SMARTA secondary effector cells with heightened functional avidity (as measured by their ability to make IFNγ in response to ex vivo restimulation with decreasing concentrations of peptide), limited contraction after pathogen clearance and stable maintenance secondary memory T cell populations. In contrast, transfer of SMARTA memory cells into naïve hosts prior to secondary Lm-gp61 challenge, which resulted in a more extended infectious period, resulted in poor functional avidity, increased death during the contraction phase and poor maintenance of secondary memory T cell populations. The modulation of functional avidity during the secondary Th1 response was independent of differences in antigen load or persistence. Instead, the inflammatory environment strongly influenced the function of the secondary Th1 response, as inhibition of IL-12 or IFN-I activity respectively reduced or increased the functional avidity of secondary SMARTA effector cells following rechallenge in a naïve secondary hosts. Our findings demonstrate that secondary effector T cells exhibit inflammation-dependent differences in functional avidity and memory potential, and have direct bearing on the design of strategies aimed at boosting memory T cell responses.