Oxygen Vacancy-Controlled CuOx/N,Se Co-Doped Porous Carbon via Plasma-Treatment for Enhanced Electro-Reduction of Nitrate to Green Ammonia.

The electrochemical nitrate reduction reaction (NO3RR) is of significance in regards of environmentally friendly issues and green ammonia production. However, relatively low performance with a competitive hydrogen evolution reaction (HER) is a challenge to overcome for the NO3RR. In this study, oxygen vacancy-controlled copper oxide (CuOx) catalysts through a plasma treatment are successfully prepared and supported on high surface area porous carbon that are co-doped with N, Se species for its enhanced electrochemical properties. The oxygen vacancy-increased CuOx catalyst supported on the N,Se co-doped porous carbon (CuOx-H/NSePC) exhibited the highest NO3RR performance with faradaic efficiency (FE) of 87.2% and yield of 7.9 mg cm-2 h-1 for the ammonia production, representing significant enhancements of FE and ammonia yield as compared to the un-doped or the oxygen vacancy-decreased catalysts. This high performance should be attributed to a significant increase in the catalytic active sites with facilitated energetics from strategies of doping the catalytic materials and weakening the N─O bonding strength for the adsorption of NO3 - ions on the modulated oxygen vacancies. This results show a promise that co-doping of heteroatoms and regulating of oxygen vacancies can be key factors for performance enhancement, suggesting new guidelines for effective catalyst design of NO3RR.

Comparing the effectiveness of game literacy education and game coding education in improving problematic internet gaming.

Objective: Problematic internet gaming by adolescents has been thought to be associated with low self-esteem, depression, anxiety, and attention problems. We hypothesized that both game literacy and coding education would effectively improve problematic internet use. However, game coding education would be more effective in enhancing self-esteem and social anxiety in adolescents than game literacy education. Methods: A total of 733 adolescent volunteers were included and randomly assigned to either the game coding education or game literacy education programs. Both programs consisted of eight sessions, each lasting 45 minutes, over four weeks. The coding education sessions included game planning and development lessons and allowed students to create the game's characters, stages, and tutorials directly using Scratch, a free coding program. Game literacy education sessions included lessons on enjoying gaming with a healthy rationale and etiquette. Data on demographics, gaming patterns, and psychological status, including positive/negative perceptions of online games, depression, social anxiety, and self-esteem, were collected. Results: Both game coding and game literacy education significantly improved YIAS scores compared to baseline, and there was no significant difference in the YIAS scores between the two groups after the interventions. In the hierarchical logistic regression analysis of all participants, higher YIAS scores, stronger negative perceptions of gaming, and lower attention problem scores at baseline predicted lower levels of internet gaming addiction after interventions. In the hierarchical logistic regression analysis among individuals with game coding education, higher YIAS scores, stronger negative perceptions of gaming, lower attention problem scores, and higher self-esteem scores at baseline predicted lower levels of internet gaming addiction after intervention. In addition, game coding education greatly improved negative perceptions of games, self-esteem, and social anxiety compared to game literacy education. Conclusion: Both game literacy and game coding education effectively mitigate internet game addiction. However, game coding education effectively mitigated problematic internet gaming by improving negative perceptions of games, self-esteem, and social anxiety in adolescents. We found that the application of knowledge by students in creating their own games was more effective than simply developing a conceptual understanding of the games.

Targeting class A GPCRs for hard tissue regeneration.

G protein-coupled receptors (GPCRs) play important roles in various pathogeneses and physiological regulations. Owing to their functional diversity, GPCRs are considered one of the primary pharmaceutical targets. However, drugs targeting GPCRs have not been developed yet to regenerate hard tissues such as teeth and bones. Mesenchymal stromal cells (MSCs) have high proliferation and multi-lineage differentiation potential, which are essential for hard tissue regeneration. Here, we present a strategy for targeting class A GPCRs for hard tissue regeneration by promoting the differentiation of endogenous MSCs into osteogenic and odontogenic progenitor cells. Through in vitro screening targeted at class A GPCRs, we identified six target receptors (LPAR1, F2R, F2RL1, F2RL2, S1PR1, and ADORA2A) and candidate drugs with potent biomineralization effects. Through a combination of profiling whole transcriptome and accessible chromatin regions, we identified that p53 acts as a key transcriptional activator of genes that modulate the biomineralization process. Moreover, the therapeutic potential of class A GPCR-targeting drugs was demonstrated in tooth pulpotomy and calvarial defect models. The selected drugs revealed potent regenerative effects in both tooth and bone defects, represented by newly formed highly mineralized regions. Consequently, this study provides translational evidence for a new regenerative strategy for damaged hard tissue.

ProLonged Liposomal Delivery of TLR7/8 Agonist for Enhanced Cancer Vaccine.

Despite numerous studies on cancer treatment, cancer remains a challenging disease to cure, even after decades of research. In recent years, the cancer vaccine has emerged as a promising approach for cancer treatment, offering few unexpected side effects compared to existing therapies. However, the cancer vaccine faces obstacles to commercialization due to its low efficacy. Particularly, the Toll-like receptor (TLR) adjuvant system, specifically the TLR 7/8 agonist, has shown potential for activating Th1 immunity, which stimulates both innate and adaptive immune responses through T cells. In this study, we developed ProLNG-S, a cholesterol-conjugated form of resiquimod (R848), to enhance immune efficacy by stimulating the immune system and reducing toxicity. ProLNG-S was formulated as ProLNG-001, a positively charged liposome, and co-administered with ovalbumin (OVA) protein in the B16-OVA model. ProLNG-001 effectively targeted secondary lymphoid organs, resulting in a robust systemic anti-tumor immune response and tumor-specific T cell activation. Consequently, ProLNG-001 demonstrated potential for preventing tumor progression and improving survival compared to AS01 by enhancing anti-tumor immunity.

Performance Promotion of Multipurpose Catalysts Using Increased Oxygen Vacancy Amounts by Charge-Mismatched Doping.

Modulating the oxygen vacancy (V0) in nanostructures has opened a new avenue for efficient catalyst design, facilitating biomass oxidation reactions and electrocatalytic properties. In this study, we have investigated the properties of NiO-based catalysts with varying degrees of V0 achieved through ion doping of the catalyst with cations of different oxidation states (TM3+) or the same valence state (TM2+) as Ni2+ in the NiO matrix. By introducing charge-mismatched dopants, we enhanced the concentration of V0 in the NiO catalyst, resulting in remarkable selectivity (∼50%) for the conversion of 2,5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA), as well as a lower overpotential in the oxygen evolution reaction (OER). We believe that charge-mismatched doping offers a novel avenue for optimizing defect engineering in oxide-based catalysts, which can enable more efficient biomass conversion and water splitting. These findings have made a significant contribution to the field of multipurpose catalysis and hold the potential to inspire new catalyst designs that would usher in a more sustainable future.

Responsiveness in interracial interactions.

Perceived responsiveness-feeling understood, validated, and cared for-is critical for wellbeing and successful relationships, yet these feelings are experienced less frequently in interracial interactions than in same race-interactions. In this article, we synthesize recent research on responsiveness in interracial interactions and relationships. We first highlight how responsiveness differs in interracial versus same-race contexts. We next discuss the role of cross-race partners' goals and motivations in responsiveness, with particular attention to the ways in which self-presentation goals undermine responsiveness as well as emerging research on goals and motivations that may facilitate responsiveness in interracial interactions. Finally, we discuss how a contextual factor, the salience of race, influences responsiveness in interracial interactions.

Functional expression of oxytocin receptors in pulp-dentin complex.

Dental pulp-derived stromal cells (DPSCs) are a crucial cell population for maintaining the tissue integrity of the pulp-dentin complex. The oxytocin receptor (OXTR), a member of the G protein-coupled receptor (GPCR) superfamily, plays versatile roles in diverse biological contexts. However, the role of OXTR in dental pulp has not yet been fully understood. Here, we demonstrate the biological functions and significance of OXTR in DPSCs through a multidisciplinary approach. Microarray data of 494 GPCR genes revealed high OXTR expression in human DPSCs (hDPSCs). Blocking OXTR activity increased the expression of osteogenic and odontogenic marker genes, promoting hDPSC differentiation. Additionally, we found that OXTR is involved in extracellular matrix (ECM) remodeling through the regulation of the gene expression related to ECM homeostasis. We further demonstrated that these genetic changes are mediated by trascriptional activity of Yes-associated protein (YAP). Based on the results, a preclinical experiment was performed using an animal model, demonstrating that the application of an OXTR inhibitor to damaged pulp induced significant hard tissue formation. These results provide new insight into the oxytocin-OXTR system in the regenerative process of pulp-dentin complex.

Mn-Dopant Differentiating the Ru and Ir Oxidation States in Catalytic Oxides Toward Durable Oxygen Evolution Reaction in Acidic Electrolyte.

Designing an efficient and durable electrocatalyst for the sluggish oxygen evolution reaction (OER) at the anode remains the foremost challenge in developing proton exchange membrane (PEM) electrolyzers. Here, a highly active and durable cactus-like nanoparticle with an exposed heterointerface between the IrO2 and the low oxidation state Ru by introducing a trace amount of Mn dopant is reported. The heterostructure fabrication relies on initial mixing of the Ru and Ir phases before electrochemical oxidation to produce a conjoined Ru/IrO2 heterointerface. Benefitting from electron transfer at the heterointerface, the low oxidation state Ru species shows excellent initial activity, which is maintained even after 180 h of continuous OER test. In a half-cell test, the Mn-doped RuIr nanocactus (Mn-RuIr NCT) achieves a mass activity of 1.85 A mgIr+Ru -1 at 1.48 VRHE , which is 139-fold higher than that of commercial IrO2 . Moreover, the superior electrocatalytic performance of Mn-RuIr NCT in the PEM electrolysis system ensures its viability in practical uses. The results of the excellent catalytic performance for acidic OER indicate that the heterostructuring robust rutile IrO2 and the highly active Ru species with a low oxidation state on the catalyst surface drive a synergistic effect.

Mechanisms of somatic transformation in inherited bone marrow failure syndromes.

Inherited bone marrow failure syndromes (IBMFS) cause hematopoietic stem progenitor cell (HSPC) failure due to germline mutations. Germline mutations influence the number and fitness of HSPC by various mechanisms, for example, abnormal ribosome biogenesis in Shwachman-Diamond syndrome and Diamond-Blackfan anemia, unresolved DNA cross-links in Fanconi anemia, neutrophil maturation arrest in severe congenital neutropenia, and telomere shortening in short telomere syndrome. To compensate for HSPC attrition, HSPCs are under increased replication stress to meet the need for mature blood cells. Somatic alterations that provide full or partial recovery of functional deficit implicated in IBMFS can confer a growth advantage. This review discusses results of recent genomic studies and illustrates our new understanding of mechanisms of clonal evolution in IBMFS.

Megastudies improve the impact of applied behavioural science.

Policy-makers are increasingly turning to behavioural science for insights about how to improve citizens' decisions and outcomes1. Typically, different scientists test different intervention ideas in different samples using different outcomes over different time intervals2. The lack of comparability of such individual investigations limits their potential to inform policy. Here, to address this limitation and accelerate the pace of discovery, we introduce the megastudy-a massive field experiment in which the effects of many different interventions are compared in the same population on the same objectively measured outcome for the same duration. In a megastudy targeting physical exercise among 61,293 members of an American fitness chain, 30 scientists from 15 different US universities worked in small independent teams to design a total of 54 different four-week digital programmes (or interventions) encouraging exercise. We show that 45% of these interventions significantly increased weekly gym visits by 9% to 27%; the top-performing intervention offered microrewards for returning to the gym after a missed workout. Only 8% of interventions induced behaviour change that was significant and measurable after the four-week intervention. Conditioning on the 45% of interventions that increased exercise during the intervention, we detected carry-over effects that were proportionally similar to those measured in previous research3-6. Forecasts by impartial judges failed to predict which interventions would be most effective, underscoring the value of testing many ideas at once and, therefore, the potential for megastudies to improve the evidentiary value of behavioural science.

Directing transition metal-based oxygen-functionalization catalysis.

This review presents the recent progress of oxygen functionalization reactions based on non-electrochemical (conventional organic synthesis) and electrochemical methods. Although both methods have their advantages and limitations, the former approach has been used to synthesize a broader range of organic substances as the latter is limited by several factors, such as poor selectivity and high energy cost. However, because electrochemical methods can replace harmful terminal oxidizers with external voltage, organic electrosynthesis has emerged as greener and more eco-friendly compared to conventional organic synthesis. The progress of electrochemical methods toward oxygen functionalization is presented by an in-depth discussion of different types of electrically driven-chemical organic synthesis, with particular attention to recently developed electrochemical systems and catalyst designs. We hope to direct the attention of readers to the latest breakthroughs of traditional oxygen functionalization reactions and to the potential of electrochemistry for the transformation of organic substrates to useful end products.

Asymmetric Synthesis of 1,2-Dihydronaphthalene-1-ols via Copper-Catalyzed Intramolecular Reductive Cyclization.

We describe a copper-catalyzed intramolecular reductive cyclization of easily accessible benz-tethered 1,3-dienes containing a ketone moiety. This process provided biologically active 1,2-dihydronaphthalene-1-ol derivatives in good yields with excellent enantio- and diastereoselectivity. Mechanistic investigations using density functional theory revealed that (Z)- and (E)-allylcopper intermediates formed in situ from the diene and copper catalyst undergo isomerization and selective intramolecular allylation of the (E)-allylcopper form of the major product through a six-membered boatlike transition state. The resulting products were further transformed to fully saturated naphthalene-1-ols by reactions of the olefin moiety.

Rugosic acid A, derived from Rosa rugosa Thunb., is novel inhibitory agent for NF-κB and IL-6/STAT3 axis in acute lung injury model.

Rosa rugosa Thunb., is as a medicinal plant known for anti-diabetic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of in R. rugosa extract (95% EtOH) remain unknown. Here, we hypothesized that terpenoid structure, the most abundant constituents in R. rugosa extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-13) and newly purified 11-methoxy polisin A, and 13-methoxy bisaborosaol F using NMR and ESI-MS and to screened their effects on NO production in LPS-induced macrophages. Rugosic acid A (RA) induced to ameliorate NO production, iNOS, and pro-inflammatory cytokines associated with the NF-κB. And, RA suppressed IL-6 secretion and IL-6-mediated STAT3 activation in LPS-mediated inflammation. In addition, RA was evaluated in LPS-mediated acute lung injury (ALI) model similar to acute pneumonia. Our results suggested that RA was suppressed to translocate nuclear NF-κB and IL-6-mediated STAT3 activation. Finally, RA led to amelioration of ALI by decreasing myeloperoxidase (MPO) and inhibiting phosphorylation of NF-κB and STAT3. Our group originally found that R. rugosa extract had new methoxy compounds and RA may be alternative natural agent for acute pneumonia similar to severe acute respiratory syndrome by coronavirus.

Asymmetric Synthesis of 1-Benzazepine Derivatives via Copper-Catalyzed Intramolecular Reductive Cyclization.

An asymmetric construction of enantioenriched 2,3-substituted-1-benzazepine derivatives containing a cyclic tertiary amine moiety was developed by copper-catalyzed reductive intramolecular cyclization of (E)-dienyl arenes with a tethered ketimine. This protocol involves tandem chemo-, regio-, and enantioselective hydrocupration and asymmetric cyclization in the presence of a chiral bisphosphine-copper catalyst. Under mild conditions, a broad range of 1-benzazepine derivatives was obtained in good to high yields with high degrees of diastereoselectivity and enantioselectivity.

Copper-Catalyzed Asymmetric Reduction of ß,ß-Disubstituted Alkenylboramides.

A highly enantioselective copper-catalyzed reduction of ß,ß-disubstituted alkenylboron compounds was developed using hydrosilane. The copper hydride catalyst coordinated with chiral Josiphos ligand efficiently discriminated ß-geminal substituents to generate corresponding ß-chiral alkylboramides with excellent enantioselectivities up to 99% ee. The enantioselective reduction protocol provides a facile approach to ß-chiral alkylboron compounds with less sterically discriminating substituents and spans a wide substrate range including aryl-substituted borylalkenes with effective functional group tolerance.

Effects of Serotonin and Slow-Release 5-Hydroxytryptophan on Gastrointestinal Motility in a Mouse Model of Depression.

BACKGROUND & AIMS: Mood disorders and constipation are often comorbid, yet their shared etiologies have rarely been explored. The neurotransmitter serotonin (5-HT) regulates central nervous system and enteric nervous system (ENS) development and long-term functions, including gastrointestinal (GI) motility and mood. Therefore, defects in neuron production of 5-HT might result in brain and intestinal dysfunction. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT biosynthesis. A variant of TPH2 that encodes the R441H substitution (TPH2-R441H) was identified in individuals with severe depression. We studied mice with an analogous mutation (TPH2-R439H), which results in a 60%-80% decrease in levels of 5-HT in the central nervous system and behaviors associated with depression in humans. Feeding chow that contains 5-HTP slow release (5-HTP SR) to TPH2-R439H mice restores levels of 5-HT in the central nervous system and reduces depressive-like behaviors. METHODS: We compared the effects of feeding chow, with or without 5-HTP SR, to mice with the TPH2-R439H mutation and without this mutation (control mice). Myenteric and submucosal plexuses were isolated from all 4 groups of mice, and immunocytochemistry was used to quantify total enteric neurons, serotonergic neurons, and 5-HT-dependent subsets of neurons. We performed calcium imaging experiments to evaluate responses of enteric neurons to tryptamine-evoked release of endogenous 5-HT. In live mice, we measured total GI transit, gastric emptying, small intestinal transit, and propulsive colorectal motility. To measure colonic migrating motor complexes (CMMCs), we isolated colons and constructed spatiotemporal maps along the proximodistal length to quantify the frequency, velocity, and length of CMMCs. We measured villus height, crypt perimeter, and relative densities of enterochromaffin and enteroendocrine cells in small intestinal tissue. RESULTS: Levels of 5-HT were significantly lower in enteric neurons from TPH2-R439H mice than from control mice. TPH2-R439H mice had abnormalities in ENS development and ENS-mediated GI functions, including reduced motility and intestinal epithelial growth. Total GI transit and propulsive colorectal motility were slower in TPH2-R439H mice than controls, and CMMCs were slower and less frequent. Villus height and crypt perimeter were significantly decreased in colon tissues from TPH2-R439H mice compared with controls. Administration of 5-HTP SR to adult TPH2-R439H mice restored 5-HT to enteric neurons and reversed these abnormalities. Adult TPH2-R439H mice given oral 5-HTP SR had normalized numbers of enteric neurons, total GI transit, and colonic motility. Intestinal tissue from these mice had normal measures of CMMCs and enteric epithelial growth CONCLUSIONS: In studies of TPH2-R439H mice, we found evidence for reduced release of 5-HT from enteric neurons that results in defects in ENS development and GI motility. Our findings indicate that neuron production of 5-HT links constipation with mood dysfunction. Administration of 5-HTP SR to mice restored 5-HT to the ENS and normalized GI motility and growth of the enteric epithelium. 5-HTP SR might be used to treat patients with intestinal dysfunction associated with low levels of 5-HT.

Asymmetric Synthesis of γ-Hydroxy Pinacolboronates through Copper-Catalyzed Enantioselective Hydroboration of α,ß-Unsaturated Aldehydes.

We report a copper-catalyzed enantioselective hydroboration of α,ß-unsaturated aldehydes with pinacolborane. α,ß-Unsaturated aldehydes were converted to the corresponding γ-pinacolboronate alcohols in good yields and enantioselectivities through consecutive hydroboration of the C═O and C═C bonds. This process provides simple access to the hydroborated product of allylic alcohols, and the resulting γ-pinacolboronate alcohols could be utilized in various transformations.

Copper-Catalyzed Regioselective and Diastereoselective Synthesis of Borylated 1-Benzo[ b]azepines.

A practical regioselective and diastereoselective synthesis of functionalized 1-benzo[ b]azepines by copper-catalyzed intramolecular cyclization has been developed. The reaction involves borylcupration of a mixture of ( E/ Z)-1,3-dienes, followed by capture of the generated ( Z)-allylcopper species with an imine to produce 7-membered N-heterocycles as single diastereomers. The reaction is applicable to various ( E/ Z)-dienyl arenes with an imine moiety at the ortho-position, including aryl, alkyl, and heterocyclic aldimines, and ketimines, affording borylated 2,3- cis-substituted 1-benzo[ b]azepines in good yields.

Brain-Gut Axis: Clinical Implications.

This article provides an overarching view of what is currently known about the physiology of the brain-gut axis in both health and disease and how these concepts apply to irritable bowel syndrome, the most common functional gastrointestinal disorder in pediatrics.

D-Amino Acid Analogues of the Antimicrobial Peptide CDT Exhibit Anti- Cancer Properties in A549, a Human Lung Adenocarcinoma Cell Line.

INTRODUCTION: The importance of the antitumor activity of some antimicrobial peptides (AMPs) is being increasingly recognized. The antimicrobial peptide, tachyplesin, has been shown to exhibit anticancer properties and a linear, cysteine deleted analogue (CDT), was found to retain its antibacterial function. OBJECTIVES: The objective was to test CDT and related analogues against normal mammalian, bacterial, and cancer cells to determine their effectiveness and then utilize specific assays to determine a possible mechanism of action. METHODS: We used sequence reversal and D-amino acids to synthesize four CDT analogues by solid phase peptide synthesis. A number of assays were used including liposome dye-leakage, antibacterial activity against both Gram-positive and Gram-negative bacterial strains, hemolytic assays, methyl thiazolyl tetrazolium (MTT), and apoptosis to examine their effectiveness as both AMPs and anti-cancer peptides (ACPs). We then tested the analogues for their ability to inhibit proliferation of the human lung cancer cell line, A549. RESULTS: We found that D-CDT exhibited the best bactericidal properties of those tested and was not damaging to red blood cells. Both D-CDT and reverse D-CDT showed a dose-dependent reduction of cell viability. However, D-CDT was most effective with an IC50 of 9.814 µM, a value 9-fold lower than that calculated for reverse D-CDT (90.16 µM). Apoptosis does not appear to be a mechanism by which D-CDT exerts its anticancer properties since > 100 µM was required to increase activation of caspase 3. Moreover, the ERK1/2 pathway is also unlikely since only a modest (20%) decrease of activity was observed with > 100 µM D-CDT. However, D-CDT was found to operate via a hyaluronan (HA)-dependent mechanism as pretreatment of the cells with hyaluronidase decreased the cytotoxic effects of D-CDT on A549 cells and increased its IC50 29-fold to 283.9 µM. CONCLUSION: D-CDT is both an effective AMP and ACP, and likely exerts its anticancer effects through both membranolytic as well as an HA-mediated mechanism.