Search

Abstract Soluble methane monooxygenase (sMMO) oxidizes a wide range of carbon feedstocks (C1 to C8) directly using intracellular NADH and is a useful means in developing green routes for industrial manufacturing of chemicals. However, the high-throughput biosynthesis of active recombinant sMMO and the ensuing catalytic oxidation have so far been unsuccessful due to the structural and functional complexity of sMMO, comprised of three functionally complementary components, which remains a major challenge for its industrial applications. Here we develop a catalytically active miniature of sMMO (mini-sMMO), with a turnover frequency of 0.32 s−1, through an optimal reassembly of minimal and modified components of sMMO on catalytically inert and stable apoferritin scaffold. We characterise the molecular characteristics in detail through in silico and experimental analyses and verifications. Notably, in-situ methanol production in a high-cell-density culture of mini-sMMO-expressing recombinant Escherichia coli resulted in higher yield and productivity (~ 3.0 g/L and 0.11 g/L/h, respectively) compared to traditional methanotrophic production.

All‐solid‐state Li‐metal battery (ASSLB) represents advantageous energy storage system for automotive applications. For ASSLB, inorganic solid electrolyte is essential in determining safety and cycling performance. However, significant challenges persist in practical construction of ASSLB with optimized electrolyte. Specifically, electrolyte's structural instability influencing its electrochemical performance remains critical issue within typical operating temperatures for ASSLB in electric vehicles. Herein, this challenge is fundamentally addressed by substituting trace amount of lithium with cadmium, which lacks crystal field stabilization energy. This strategy of atomic interaction modification has induced electrolyte's structural distortion and electronic alteration by deliberately introducing disorder at local lithium sites. Li symmetric cell with cadmium‐substituted antiperovskite solid electrolyte exhibits outstanding critical current density of 11.5 mA cm−2 (5.75 mAh cm−2) and excellent stability for 3000 h at 10.0 mA cm−2 (5.0 mAh cm−2). This study highlights explicit research direction for breakthrough of ASSLB, focusing on understanding how local distortion affects complex inorganic materials.

Abstract Background In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. Methods To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. Results CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244−/− bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. Conclusion Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.

Everyday speech communication often occurs in environments with background noise, and the impact of noise on speech recognition can vary depending on factors such as noise type, noise intensity, and the listener’s hearing ability. However, the extent to which neural mechanisms in speech understanding are influenced by different types and levels of noise remains unknown. This study aims to investigate whether individuals exhibit distinct neural responses and attention strategies depending on noise conditions. We recorded electroencephalography (EEG) data from 20 participants with normal hearing (13 males) and evaluated both neural tracking of speech envelopes and behavioral performance in speech understanding in the presence of varying types of background noise. Participants engaged in an EEG experiment consisting of two separate sessions. The first session involved listening to a 12-min story presented binaurally without any background noise. In the second session, speech understanding scores were measured using matrix sentences presented under speech-shaped noise (SSN) and Story noise background noise conditions at noise levels corresponding to sentence recognitions score (SRS). We observed differences in neural envelope correlation depending on noise type but not on its level. Interestingly, the impact of noise type on the variation in envelope tracking was more significant among participants with higher speech perception scores, while those with lower scores exhibited similarities in envelope correlation regardless of the noise condition. The findings suggest that even individuals with normal hearing could adopt different strategies to understand speech in challenging listening environments, depending on the type of noise.

Abstract Background Methylphenidate (MPH) is the most frequently prescribed medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the safety of its long-term use remain unclear. In particular, real-world evidence of long-term MPH treatment regarding the risk of depression, conduct disorders, and psychotic disorders in children and adolescents is needed. This study aimed to compare the risks of depression, conduct disorder, and psychotic disorder between long- and short-term MPH treatments in children and adolescents. Methods This population-based cohort study used a nationwide claims database of all patients with ADHD in South Korea. Patients aged less than 18 years who were prescribed MPH were included in the study. Long- and short-term MPH were defined as > 1 year, and

Abstract Although a variety of urinary cancer markers are available for in vitro diagnosis, inherent problems of urine environment—containing various inorganic/organic ions/molecules that vary in concentration over a 20‐fold range or more and significantly attenuate antibody avidity for markers—render conventional immunoassays unsuitable, remaining unresolved and a major challenge. Here we developed a 3D‐plus‐3D (3p3) immunoassay method, based on a single‐step urinary marker detection by 3D‐antibody probes, which are free of steric hindrance and capable of omnidirectional capture of markers in a 3D solution. The 3p3 immunoassay showed an excellent performance in the diagnosis of prostate cancer (PCa) through detecting PCa‐specific urinary engrailed‐2 protein, demonstrating 100% sensitivity and 100% specificity with the urine specimens of PCa‐related and other related disease patients and healthy individuals. This innovative approach holds a great potential in opening up a novel clinical route for precise in vitro cancer diagnosis and also pushing urine immunoassay closer to more widespread adoption.

TIGIT is an immune checkpoint receptor that is expressed on subsets of activated T cells and natural killer (NK) cells. Several ligands for TIGIT, including poliovirus receptor (PVR), are expressed on cancer cells and mediate inhibitory signaling to suppress antitumor activities of the immune cells. Many studies support that the TIGIT signaling is a potential target for cancer immunotherapy. We developed an IgG4-type monoclonal antibody against human TIGIT, designated as MG1131, using a phage display library of single-chain variable fragments (scFvs). MG1131 interacts with TIGIT much more tightly than PVR does. The crystal structure of a scFv version of MG1131 bound to TIGIT was determined, showing that MG1131 could block the PVR-TIGIT interaction and thus the immunosuppressive signaling of TIGIT. Consistently, MG1131 is bound to TIGIT-expressing cells and interferes with PVR binding to these cells. Moreover, MG1131 increased NK cell-mediated tumor killing activities, inhibited immunosuppressive activity of regulatory T (Treg) cells from healthy donors, and restored interferon-γ secretion from peripheral blood mononuclear cells derived from multiple myeloma patients. MG1131 also increased T cell infiltration to the tumor site and inhibited tumor growth in mice. Collectively, these data indicate that MG1131 modulates the effector functions of T cells and NK cells positively and Treg cells negatively.

Abstract Heterologous protein production in Saccharomyces cerevisiae is a useful and effective strategy with many advantages, including the secretion of proteins that require posttranslational processing. However, heterologous proteins in S. cerevisiae are often secreted at comparatively low levels. To improve the production of the heterologous protein, human granulocyte colony‐stimulating factor (hG‐CSF) in S. cerevisiae, a secretion‐enhancing peptide cassette including an hIL‐1β‐derived pro‐peptide, was added and used as a secretion enhancer to alleviate specific bottlenecks in the yeast secretory pathway. The effects of three key parameters—N‐glycosylation, net negative charge balance, and glycine‐rich flexible linker—were investigated in batch cultures of S. cerevisiae. Using a three‐stage design involving screening, selection, and optimization, the production and secretion of hG‐CSF by S. cerevisiae were significantly increased. The amount of extracellular mature hG‐CSF produced by the optimized pro‐peptide after the final stage increased by 190% compared to that of the original pro‐peptide. Although hG‐CSF was used as the model protein in the current study, this strategy is applicable to the enhanced production of other heterologous proteins, using S. cerevisiae as the host.

All‐solid‐state Li‐metal battery (ASSLB) represents advantageous energy storage system for automotive applications. For ASSLB, inorganic solid electrolyte is essential in determining safety and cycling performance. However, significant challenges persist in practical construction of ASSLB with optimized electrolyte. Specifically, electrolyte's structural instability influencing its electrochemical performance remains critical issue within typical operating temperatures for ASSLB in electric vehicles. Herein, this challenge is fundamentally addressed by substituting trace amount of lithium with cadmium, which lacks crystal field stabilization energy. This strategy of atomic interaction modification has induced electrolyte's structural distortion and electronic alteration by deliberately introducing disorder at local lithium sites. Li symmetric cell with cadmium‐substituted antiperovskite solid electrolyte exhibits outstanding critical current density of 11.5 mA cm−2 (5.75 mAh cm−2) and excellent stability for 3000 h at 10.0 mA cm−2 (5.0 mAh cm−2). This study highlights explicit research direction for breakthrough of ASSLB, focusing on understanding how local distortion affects complex inorganic materials. [ABSTRACT FROM AUTHOR]

Background: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. Methods: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. Results: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244−/− bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. Conclusion: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients. [ABSTRACT FROM AUTHOR]

This article, titled "Profiling markers of silicosis in a Victorian cohort of engineered stone workers," discusses the ongoing issue of silicosis, a lung disease caused by exposure to silica dust, particularly in the context of engineered stone workers. The study aims to understand the disease better by determining the silica load and identifying proteins present in the bronchoalveolar lavage fluid (BALF) of silicosis patients compared to non-diseased controls. The researchers found that there was no significant relationship between silica load and lung function measures. They also identified several proteins that may contribute to disease initiation and progression, potentially serving as biomarkers or therapeutic targets. [Extracted from the article]

Objective: The purpose of the current study was to examine the prevalence of attention deficit hyperactivity disorder (ADHD) in girls with central precocious puberty. Method: Girls with central precocious puberty were prospectively recruited from the pediatric clinic. Screening was done with ADHD Rating Scale (ADHD-RS) and Child Behavior Checklist (CBCL). Those who screened positive on ADHD-RS were referred for the diagnostic evaluation which included a Computerized Performance Test (CPT) and a clinical interview conducted by a child adolescent psychiatrist. Results: Among the 81 girls (mean age = 8.97 ± 0.91) who completed the study, 11 girls (13.58%) were diagnosed with ADHD: 5 of them were inattentive type and 6 of them were combined type. Conclusion: The present exploratory study showed that the prevalence of ADHD in girls with central precocious was higher than the known worldwide prevalence of ADHD in children [ABSTRACT FROM AUTHOR]

The article focuses on a corrigendum related to an error in the name of one of the authors, 'Daniel Prieto-Alhambra,' in a study on the safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression.

Although a variety of urinary cancer markers are available for in vitro diagnosis, inherent problems of urine environment—containing various inorganic/organic ions/molecules that vary in concentration over a 20‐fold range or more and significantly attenuate antibody avidity for markers—render conventional immunoassays unsuitable, remaining unresolved and a major challenge. Here we developed a 3D‐plus‐3D (3p3) immunoassay method, based on a single‐step urinary marker detection by 3D‐antibody probes, which are free of steric hindrance and capable of omnidirectional capture of markers in a 3D solution. The 3p3 immunoassay showed an excellent performance in the diagnosis of prostate cancer (PCa) through detecting PCa‐specific urinary engrailed‐2 protein, demonstrating 100% sensitivity and 100% specificity with the urine specimens of PCa‐related and other related disease patients and healthy individuals. This innovative approach holds a great potential in opening up a novel clinical route for precise in vitro cancer diagnosis and also pushing urine immunoassay closer to more widespread adoption. [ABSTRACT FROM AUTHOR]

Anode‐free Li metal batteries (AFLMBs) are highly advantageous due to their high energy density, low cost, and simple fabrication. However, severe challenges, such as uncontrolled dendrite formation and low coulombic efficiency, restrict their practical application. Herein, this work introduces a silver nanoparticles incorporated p‐doped conjugated polymer (Ag‐PCP) wetting agent on the copper current collector, which promotes both uniform Li nucleation and rapid formation of a LiF‐rich solid electrolyte interphase (SEI) at the early stage, resulting in interfacial stabilization and high Li utilization efficiency. Moreover, this work verifies the interfacial fluorinated mechanism of the Ag‐PCP to efficiently achieve a favorable SEI chemistry, which serves as an intermediate process for promoting LiF formation. Benefiting from the synergistic effect of Ag–Li alloying and F‐doping chemistry of the Ag‐PCP chains, the deposited Li exhibits a compact column‐like structure with dendrite‐free morphology, and the anode‐free cells display superior cycling stability with long lifespan even under harsh conditions, with the LFP//Ag‐PCP│Cu full cell having a high capacity retention of 72% (Li inventory retention rate, 99.8%) at 1 C‐rate after 200 cycles. [ABSTRACT FROM AUTHOR]

Background: Methylphenidate (MPH) is the most frequently prescribed medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, the safety of its long-term use remain unclear. In particular, real-world evidence of long-term MPH treatment regarding the risk of depression, conduct disorders, and psychotic disorders in children and adolescents is needed. This study aimed to compare the risks of depression, conduct disorder, and psychotic disorder between long- and short-term MPH treatments in children and adolescents. Methods: This population-based cohort study used a nationwide claims database of all patients with ADHD in South Korea. Patients aged less than 18 years who were prescribed MPH were included in the study. Long- and short-term MPH were defined as > 1 year, and < 1 year, respectively. Overall, the risk of developing depressive disorder, conduct disorder and oppositional defiant disorder (ODD), and psychotic disorder were investigated. A 1:2 propensity score matching was used to balance the cohorts, and the Cox proportional hazards model was used to evaluate the safety of MPH. Results: We identified 1309 long-term and 2199 short-term MPH users. Long-term MPH use was associated with a significantly lower risk of depressive (hazard ratio [HR], 0.70 [95% confidence interval [CI] 0.55–0.88]) and conduct disorders and ODD (HR, 0.52 [95% CI 0.38–0.73]) than short-term MPH use. Psychotic disorder was not significantly associated with long-term MPH use (hazard ratio [HR], 0.83 [95% confidence interval [CI] 0.52–1.32]). Conclusions: Our findings suggest that long-term MPH use may be associated with a decreased risk of depression, conduct disorders and ODD. Moreover, the long-term use of MPH does not increase the risk of psychotic disorders. Long-term MPH administration may be considered as a favourable treatment strategy for children and adolescents with ADHD regarding depressive, conduct, and psychotic disorders. [ABSTRACT FROM AUTHOR]

We investigated whether the severity of anxiety among children undergoing endoscopy could affect sedation. We prospectively recruited patients under 18 years of age who were scheduled to undergo esophagogastroduodenoscopy (EGD). Baseline anxiety was evaluated using the Spence Children's Anxiety Scale (SCAS). Our analysis considered the type and dose of sedative drugs, degree of sedation, and complications associated with sedation according to the scale score. The mean total SCAS T-scores and each subscale score were significantly higher in the 6–12-year age group. The mean T-score among patients who exhibited irritability during EGD was higher than that among other patients, with significant differences in the Total, Obsessive Disorder, Panic Agoraphobia and General Anxiety subscales. The midazolam doses of children exhibiting irritability were more likely to need higher (p = 0.006). Other sedation-related complications were not associated with the T-scores in each subscale. Total sleep time was not associated with any T-score subscales. Anxiety levels were significantly higher among 6–12-year-olds and children exhibiting irritability. Anxiety was often associated with irritability, difficulties achieving adequate sedation during EGD, and additional sedative drug administration. We recommend higher doses or more potent drugs to facilitate endoscopy for children with high anxiety levels. [ABSTRACT FROM AUTHOR]

The phenomenon of children seemingly 'doing well' despite adversity spawned the early study of resilience, which has now expanded into a vast field of research. This article, however, is not about the resilience of children or the protective resources that they need to thrive. Locating the concept of resilience in the interactions between individuals and their social ecologies, it explores how children – as an important part of these ecologies – can be a significant protective resource for victims-/survivors of conflict-related sexual violence, and, hence, a support for resilience. It develops this argument using qualitative data from interviews with victims-/survivors of conflict-related sexual violence in Bosnia-Herzegovina (BiH), Colombia and Uganda. It further seeks to demonstrate that this linkage between children, social ecologies and resilience has broader implications for transitional justice. Specifically, the article underlines the need for transitional justice processes to give more attention to, and to invest in, the social ecologies – and the protective resources within them – that inextricably shape the lives of individuals affected by violence and human rights violations, including victims-/survivors of conflict-related sexual violence. [ABSTRACT FROM AUTHOR]

Embedded in everyday practices, food can be a rich resource for interaction design. This article focuses on eating experiences to uncover how bodily, sensory, and socio-cultural aspects of eating can be better leveraged for the design of user experience. We report a systematic literature review of 109 papers, and interviews with 18 professional chefs, providing new understandings of prior HFI research, as well as how professional chefs creatively design eating experiences. The findings inform a conceptual framework of designing for user experience leveraging eating experiences. These findings also inform implications for HFI design suggesting the value of multisensory flavor experiences, external and internal sensory stimulation and deprivation, aspects of eating for communicating meaning, and designing with contrasting pleasurable and uncomfortable experiences. The article concludes with six charts as novel generative design tools for HFI experiences focused on sensory, emotional, communicative, performative, and temporal experiences. [ABSTRACT FROM AUTHOR]

Interfacial instability between Li‐metal anode (LMA) and inorganic solid‐state electrolyte (SSE) is a critical issue in all‐solid‐state Li‐metal batteries (ASSLBs). Previous studies have focused on interface modification methodology to achieve long‐term cycling stability in ASSLBs. However, strategy establishment without an in‐depth understanding of the LMA–SSE interface is limited to a phenomenological solution. Also, the fact that rechargeable batteries are operated by behavior of charges inside electric field is frequently overlooked. Here, it is demonstrated for the first time that interface modeling based on energy band theory does effectively overcome the intrinsic vulnerability of SSE to LMA. The interfacial deterioration, due to undesirable electron transport from LMA to the SSE surface, is precluded by a titanium compound self‐induced interlayer (TSI), which forms an interfacial energy barrier. The Li symmetric cell with a TSI successfully maintains its constant overpotential over 1000 cycles and the significantly reduced impedance, whereas the cell having no interface modification exhibits erratic voltage profiles and is easily failed by repetitive charge–discharge process. This newly introduced approach is an informative tool to substantially reinforce the fundamental understanding of interfacial phenomena in all‐solid‐state batteries. Furthermore, rigorous stability requirements of automotive applications are expected to be fulfilled by the innovative interface modification. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the present study was to investigate the efficacy of combined omega-3 and Korean red ginseng supplementation on ADHD symptoms and cognitive function in children with subthreshold ADHD.Method: 120 children from 6 to 12 years with subthreshold ADHD were enrolled in this 12-week, double-blind, randomized, placebocontrolled study. The primary outcome was measured by Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Children Behavior Check List (CBCL), and neuropsychological tests assessing attention, memory, and executive function were included as secondary primary outcome measures.Results: Significant effects on the scores of ADHDRS, as well as several subscales of CBCL including ADHD and attention problem subscales were revealed.Conclusion: The combination of omega-3 and Korean red ginseng may have beneficial effects in children with subthreshold ADHD. Increased clinical awareness of ADHD symptoms even at a subthreshold level is needed. [ABSTRACT FROM AUTHOR]