Morphology Control of Au-Ni Hybrid Nanoparticles: Exploring Heterostructures and Optical Tuning.

Hybrid nanoparticles (NPs) have attracted considerable attention because of their ability to provide diverse properties by integrating the inherent properties of multiple components; however, synthetic strategies to control their morphology remain unexplored. In this study, a new method was used to control the morphology and optical properties of Au-Ni heterostructure (ANH) NPs. Unique morphological changes were observed by varying the Au/Ni precursor ratio from 2:1 to 1:4, exhibiting a shape transformation from dumbbell-like to quasi-spherical owing to the Ni NP size expansion, whereas the Au NP maintained their size. Moreover, increasing the Ni ratio induced plasmonic band broadening and wavelength redshift, resulting in color changes from red to navy and black. In terms of the structure, the atomic orientation of the crystallite showed that even a large lattice mismatch can result in heterojunctions at the NPs. In addition, the reaction aliquots uncovered heterogeneous nucleation and growth of ANH NPs in the colloidal system, demonstrating Ni reduction on the preformed Au NP owing to the reduction in potential gap. This study provides new insights into controlling the morphology of hybrid NPs using colloidal synthesis and the design of optimized materials for various applications.

Enhanced stability of boron modified NiFe hydroxide for oxygen evolution reaction.

The introduction of non-metal elements including boron has been identified as a significant means to enhance oxygen evolution reaction (OER) performance in NiFe-based catalysts. To understand the catalytic activity and stability, recent attention has widened toward the Fe species as a potential contributor, prompting exploration from various perspectives. Here, boron incorporation in NiFe hydroxide achieves significantly enhanced activity and stability compared to the boron-free NiFe hydroxide. The boron inclusion in NiFe hydroxide is found to show exceptionally improved stability from 12 to 100 hours at a high current density (200 mA cm-2). It facilitates the production and redeposition of OER-active, high-valent Fe species in NiFe hydroxide based on the operando Raman, UV-vis, and X-ray absorption spectroscopy analysis. It is proposed that preserving a homogenous distribution of Fe across the boron-containing catalyst surface enhances OER stability, unlike the bare NiFe hydroxide electrocatalyst, which exhibits uneven Fe dissolution, confirmed through elementary mapping analysis. These findings shed light on the potential of anionic regulation to augment the activity of iron, an aspect not previously explored in depth, and thus are expected to aid in designing practical OER electrocatalysts.

Effect of 3D-printed polycaprolactone/osteolectin scaffolds on the odontogenic differentiation of human dental pulp cells.

Cell-based tissue engineering often requires the use of scaffolds to provide a three-dimensional (3D) framework for cell proliferation and tissue formation. Polycaprolactone (PCL), a type of polymer, has good printability, favorable surface modifiability, adaptability, and biodegradability. However, its large-scale applicability is hindered by its hydrophobic nature, which affects biological properties. Composite materials can be created by adding bioactive materials to the polymer to improve the properties of PCL scaffolds. Osteolectin is an odontogenic factor that promotes the maintenance of the adult skeleton by promoting the differentiation of LepR+ cells into osteoblasts. Therefore, the aim of this study was to evaluate whether 3D-printed PCL/osteolectin scaffolds supply a suitable microenvironment for the odontogenic differentiation of human dental pulp cells (hDPCs). The hDPCs were cultured on 3D-printed PCL scaffolds with or without pores. Cell attachment and cell proliferation were evaluated using EZ-Cytox. The odontogenic differentiation of hDPCs was evaluated by alizarin red S staining and alkaline phosphatase assays. Western blot was used to evaluate the expression of the proteins DSPP and DMP-Results: The attachment of hDPCs to PCL scaffolds with pores was significantly higher than to PCL scaffolds without pores. The odontogenic differentiation of hDPCs was induced more in PCL/osteolectin scaffolds than in PCL scaffolds, but there was no statistically significant difference. 3D-printed PCL scaffolds with pores are suitable for the growth of hDPCs, and the PCL/osteolectin scaffolds can provide a more favorable microenvironment for the odontogenic differentiation of hDPCs.

Appendectomy and the Risk of Parkinson's Disease: A Korean Nationwide Study.

BACKGROUND: The vermiform appendix is considered a potential reservoir for the abnormal α-synuclein aggregate in Parkinson's disease (PD). Previous epidemiologic evidence on the association between appendectomy and PD risk remains inconclusive, especially outside the Western world. OBJECTIVES: To investigate the association between appendectomy and PD risk in Korea. METHODS: Among 703,831 eligible adult subjects in the National Health Insurance Service sample cohort, we identified 16,122 patients who underwent appendectomy. The rest formed the control group. PD risk was assessed using time-dependent Cox regression analyses. RESULTS: The appendectomy group did not have altered risk of PD compared with the control group in either unadjusted [hazard ratio (HR) 1.32, 95% confidence interval (CI) 0.97-1.80, P = 0.08] or adjusted model (HR 1.42, CI 0.88-2.30, P = 0.15). No further statistical difference appeared when stratified by sex. CONCLUSIONS: Appendectomy is not associated with altered risk of PD in the Korean population.

Application of pseudo-parameter iteration method to nonlinear deflection analysis of an infinite beam with variable beam cross-sections on a nonlinear elastic foundation.

In this study, the nonlinear deflection of an infinite beam with variable beam cross-sections on a nonlinear elastic foundation was analyzed using the pseudo-parameter iteration method (PIM), which is a novel iterative semi-analytic method for solving ordinary/partial differential equations. To do this, we set six types of infinite beams with concave and convex shapes under static loading conditions. To calculate the nonlinear deflection of the infinite beam with variable cross-sections, the Bernoulli-Euler beam equation (fourth-order ordinary differential equation) considering changing beam flexural rigidity was introduced, and the PIM was adopted to this equation. Through the numerical experiment, it was confirmed that the nonlinear deflections calculated via the PIM are quite close to the exact solution within a few iterations. In addition, the graph of error quickly reaches the steady state error for all cases as the number of iterations increases.

Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea.

BACKGROUND AND PURPOSE: The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. METHODS: Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. RESULTS: Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively (p<0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p=0.019; and HR=1.17, 95% CI=1.03-1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p=0.034) in the CoHD group. CONCLUSIONS: Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.

Live attenuated smallpox vaccine candidate (KVAC103) efficiently induces protective immune responses in mice.

Smallpox, caused by the variola virus belonging to the genus Orthopoxvirus, is an acute contagious disease that killed 300 million people in the 20th century. Since it was declared to be eradicated and the national immunization program against it was stopped, the variola virus has become a prospective bio-weapon. It is necessary to develop a safe vaccine that protects people from terrorism using this biological weapon and that can be administered to immunocompromised people. Our previous study reported on the development of an attenuated smallpox vaccine (KVAC103). This study evaluated cellular and humoral immune responses to various doses, frequencies, and routes of administration of the KVAC103 strain, compared to CJ-50300 vaccine, and its protective ability against the wild-type vaccinia virus Western Reserve (VACV-WR) strain was evaluated. The binding and neutralizing-antibody titers increased in a concentration-dependent manner in the second inoculation, which increased the neutralizing-antibody titer compared to those after the single injection. In contrast, the T-cell immune response (interferon-gamma positive cells) increased after the second inoculation compared to that of CJ-50300 after the first inoculation. Neutralizing-antibody titers and antigen-specific IgG levels were comparable in all groups administered KVAC103 intramuscularly, subcutaneously, and intradermally. In a protective immunity test using the VACV-WR strain, all mice vaccinated with CJ-50300 or KVAC103 showed 100% survival. KVAC103 could be a potent smallpox vaccine that efficiently induces humoral and cellular immune responses to protect mice against the VACV-WR strain.

Increasing incidence of Parkinson's disease in patients with epilepsy: A Nationwide cohort study.

BACKGROUND: Although epilepsy is an uncommon comorbidity of Parkinson's disease (PD), the exact incidence of PD among the patients with epilepsy is not clarified yet. OBJECTIVES: We aimed to estimate the incidence of PD in patients with epilepsy and explore the association between epilepsy and PD. METHODS: Epilepsy patients enrolled in the National Health Insurance Service Health Screening Cohort (NHIS-HealS) (2002-2013) between 2003 and 2007 were set up as the experimental group. The major outcome was the occurrence of PD. Non-epilepsy patients were obtained through Propensity Score Matching of 'greedy nearest neighbor' algorithm in 1:1 ratio. The Cox Proportional Hazards model was used to calculate PD incidence and hazard ratio (HR). RESULTS: A total of 10,510 patients were finally included in the study, which contained 5255 patients in epilepsy and non-epilepsy groups, respectively. During the follow-up period, 85 patients with Parkinson's disease among 5255 patients with epilepsy and 57 patients with Parkinson's disease among 5255 patients without epilepsy occurred. The 10,000 Person-Year (PY), representing the number of PD patients per 10,000 per year, was 21.38 in the epilepsy group and 11.18 in the non-epilepsy group. When all variables were adjusted, it was found that the epilepsy group had a 2.19 times significantly higher risk of developing Parkinson's disease than the control group (The adjusted HR: 2.19 (95% CI, 1.55-3.12)). CONCLUSION: This study indicates an increased risk of PD in patients with epilepsy. However, further research is needed to prove an exact causal relationship between these two brain disorders.

Correction to: Enzyme­derived deer velvet extract activate the immune response in cyclophosphamide­induced immunosuppressive mice.

[This corrects the article DOI: 10.1007/s10068-023-01275-4.].

Data-centric artificial olfactory system based on the eigengraph.

Recent studies of electronic nose system tend to waste significant amount of important data in odor identification. Until now, the sensitivity-oriented data composition has made it difficult to discover meaningful data to apply artificial intelligence in terms of in-depth analysis for odor attributes specifying the identities of gas molecules, ultimately resulting in hindering the advancement of the artificial olfactory technology. Here, we realize a data-centric approach to implement standardized artificial olfactory systems inspired by human olfactory mechanisms by formally defining and utilizing the concept of Eigengraph in electrochemisty. The implicit odor attributes of the eigengraphs were mathematically substantialized as the Fourier transform-based Mel-Frequency Cepstral Coefficient feature vectors. Their effectiveness and applicability in deep learning processes for gas classification have been clearly demonstrated through experiments on complex mixed gases and automobile exhaust gases. We suggest that our findings can be widely applied as source technologies to develop standardized artificial olfactory systems.

Booster doses of an inactivated F genotype mumps vaccine enhance immunogenicity in mice.

The mumps virus (MuV) causes a highly contagious human disease characterized by swelling of the parotid glands. Although the administration of an attenuated Jeryl Lynn (JL) MuV vaccine shows efficacy in reducing the incidence of MuV infection, sporadic mumps outbreaks still occur in vaccinated populations. We have previously established that an inactivated F genotype mumps vaccine has a higher neutralizing antibody titer against diverse circulating mumps viruses in mice. Here, we aimed to develop a vaccination strategy to enhance the immune response for MuV and assess the effects of heterologous vaccination compared with homologous approaches. We administered an inactivated F genotype mumps vaccine booster following a homologous prime-boost regime and compared its efficacy with three doses of homologous JL vaccine in mice. We demonstrated robust stimulation of neutralizing antibodies and cellular immune response of interferon-γ-secreting cytotoxic T cells following administration of an inactivated F genotype mumps vaccine booster after a homologous prime-boost regime with JL. Compared with the homologous prime-boost regime, this heterologous prime-boost regime showed protective efficacy against the F genotype of MuV. These findings suggest that the heterologous vaccination strategy based on the administration of an inactivated F genotype mumps vaccine provides more effective cross-protection against circulating wild-type mumps viruses than homologous vaccination.

High Doses of ANA12 Improve Phenobarbital Efficacy in a Model of Neonatal Post-Ischemic Seizures.

Phenobarbital (PB) remains the first-line medication for neonatal seizures. Yet, seizures in many newborns, particularly those associated with perinatal ischemia, are resistant to PB. Previous animal studies have shown that in postnatal day P7 mice pups with ischemic stroke induced by unilateral carotid ligation, the tyrosine receptor kinase B (TrkB) antagonist ANA12 (N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide, 5 mg/kg) improved the efficacy of PB in reducing seizure occurrence. To meet optimal standards of effectiveness, a wider range of ANA12 doses must be tested. Here, using the unilateral carotid ligation model, we tested the effectiveness of higher doses of ANA12 (10 and 20 mg/kg) on the ability of PB to reduce seizure burden, ameliorate cell death (assessed by Fluoro-Jade staining), and affect neurodevelopment (righting reflex, negative geotaxis test, open field test). We found that a single dose of ANA12 (10 or 20 mg/kg) given 1 h after unilateral carotid ligation in P7 pups reduced seizure burden and neocortical and striatal neuron death without impairing developmental reflexes. In conclusion, ANA12 at a range of doses (10-20 mg/kg) enhanced PB effectiveness for the treatment of perinatal ischemia-related seizures, suggesting that this agent might be a clinically safe and effective adjunctive agent for the treatment of pharmacoresistant neonatal seizures.

Dementia in Australia: Clinical recommendations post-diagnosis.

The delivery of a dementia diagnosis, the information provided, and the practical advice and support arranged can have a long-lasting impact on patients and their families and deserves attention equal to that given to the assessment and investigation process. Patients and their families need a constructive yet sensitive conversation about the nature and cause of their difficulties, communicated in plain language, and tailored to their main concerns and needs. This conversation should lead to the provision of high-quality, easily accessible information. Following this, clinicians may wish to consider broaching the following dementia topics: (1) pharmacological and non-pharmacological interventions, (2) connection and integration with relevant organisations, (3, 4) application for formal support services and engagement with support teams, (5) safety in the home, (6, 7) financial planning, guardianship and legal matters, (8) driving eligibility, (9) support and education resources to family carers and (10) research initiatives and genetic information. Addressing these topics will contribute to improved disease management, which is likely to improve the dementia journey for the patient, their carer(s), and family.

The Effects of an App-Based Physical Activity Program on Colorectal Cancer Patients Undergoing Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Colorectal cancer is one of the most common malignancies worldwide. Oxaliplatin, which is used as adjuvant chemotherapy, affects quality of life by causing oxaliplatin-induced peripheral neuropathy in colorectal cancer patients. OBJECTIVES: This study examined the effects of an application (app)-based physical activity program for alleviating peripheral neuropathy symptoms in colorectal cancer patients undergoing chemotherapy. METHODS: This was a randomized controlled study that included 34 patients undergoing chemotherapy after being diagnosed with colorectal cancer. Outcomes were compared between patients who participated in a 6-week app-based physical activity program (experimental group; n = 17) and who received standard booklet education (control group; n = 17). Data were collected using questionnaires, and exercise time was recorded to evaluate intervention adherence. RESULTS: Significant differences were observed between the groups in peripheral neuropathy symptoms (F = 8.93, P = .002), interference with activities (Z = -2.55, P = .011), and quality of life (F = 7.65, P = .003). The experimental group showed significantly higher average exercise times at 1 to 4 weeks (Z = -2.10, P = .026), 5 to 6 weeks (Z = -4.02, P < .001), and 1 to 6 weeks (Z = -3.40, P = .001) than the control group. CONCLUSIONS: The app-based physical activity program had a positive effect on participants' exercise adherence and reduced peripheral neuropathy symptoms. Thus, we propose the adoption of a mobile health app that can be used at any time or place as an intervention for preventing or alleviating adverse effects during the treatment of cancer patients. IMPLICATIONS FOR PRACTICE: An app-based physical activity program using the mobile health app can be used as a nursing intervention to manage symptoms and increase the health behavior adherence in cancer patients.

Caregiver Burden of Patients With Huntington's Disease in South Korea.

OBJECTIVE: This is the first prospective cohort study of Huntington's disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers. METHODS: From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups. RESULTS: Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38-65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson-Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers' demographics, blood relation, and marital and social status did not affect the burden significantly. CONCLUSION: HD patients' neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

Nanocluster Surface Microenvironment Modulates Electrocatalytic CO2 Reduction.

The catalytic activity and product selectivity of the electrochemical CO2 reduction reaction (eCO2RR) depend strongly on the local microenvironment of mass diffusion at the nanostructured catalyst and electrolyte interface. Achieving a molecular-level understanding of the electrocatalytic reaction requires the development of tunable metal-ligand interfacial structures with atomic precision, which is highly challenging. Here, the synthesis and molecular structure of a 25-atom silver nanocluster interfaced with an organic shell comprising 18 thiolate ligands are presented. The locally induced hydrophobicity by bulky alkyl functionality near the surface of the Ag25 cluster dramatically enhances the eCO2RR activity (CO Faradaic efficiency, FECO: 90.3%) with higher CO partial current density (jCO) in an H-cell compared to Ag25 cluster (FECO: 66.6%) with confined hydrophilicity, which modulates surface interactions with water and CO2. Remarkably, the hydrophobic Ag25 cluster exhibits jCO as high as -240 mA cm-2 with FECO >90% at -3.4 V cell potential in a gas-fed membrane electrode assembly device. Furthermore, this cluster demonstrates stable eCO2RR over 120 h. Operando surface-enhanced infrared absorption spectroscopy and theoretical simulations reveal how the ligands alter the neighboring water structure and *CO intermediates, impacting the intrinsic eCO2RR activity, which provides atomistic mechanistic insights into the crucial role of confined hydrophobicity.

DW71177: A novel [1,2,4]triazolo[4,3-a]quinoxaline-based potent and BD1-Selective BET inhibitor for the treatment of acute myeloid leukemia.

The bromodomain and extraterminal domain (BET) family proteins recognize acetyl-lysine (Kac) at the histone tail through two tandem bromodomains, i.e., BD1 and BD2, to regulate gene expression. BET proteins are attractive therapeutic targets in cancer due to their involvement in oncogenic transcriptional activation, and bromodomains have defined Kac-binding pockets. Here, we present DW-71177, a potent BET inhibitor that selectively interacts with BD1 and exhibits strong antileukemic activity. X-ray crystallography, isothermal titration calorimetry, and molecular dynamic studies have revealed the robust and specific binding of DW-71177 to the Kac-binding pocket of BD1. DW-71177 effectively inhibits oncogenes comparable to the pan-BET inhibitor OTX-015, but with a milder impact on housekeeping genes. It efficiently blocks cancer-associated transcriptional changes by targeting genes that are highly enriched with BRD4 and histone acetylation marks, suggesting that BD1-selective targeting could be an effective and safe therapeutic strategy against leukemia.

Evaluation of immunogenicity-induced DNA vaccines against different SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic worldwide. As of September 2023, the number of confirmed coronavirus cases has reached over 770 million and caused nearly 7 million deaths. The World Health Organization assigned and informed the characterization of variants of concern (VOCs) to help control the COVID-19 pandemic through global monitoring of circulating viruses. Although many vaccines have been proposed, developing an effective vaccine against variants is still essential to reach the endemic stage of COVID-19. We designed five DNA vaccine candidates composed of the first isolated genotype and major SARS-CoV-2 strains from isolated Korean patients classified as VOCs, such as Alpha, Beta, Gamma, and Delta. To evaluate the immunogenicity of each genotype via homologous and heterologous vaccination, mice were immunized twice within a 3-week interval, and the blood and spleen were collected 1 week after the final vaccination to analyze the immune responses. The group vaccinated with DNA vaccine candidates based on the S genotype and the Alpha and Beta variants elicited both humoral and cellular immune responses, with higher total IgG levels and neutralizing antibody responses than the other groups. In particular, the vaccine candidate based on the Alpha variant induced a highly diverse cytokine response. Additionally, we found that the group subjected to homologous vaccination with the S genotype and heterologous vaccination with S/Alpha induced high total IgG levels and a neutralization antibody response. Homologous vaccination with the S genotype and heterologous vaccination with S/Alpha and S/Beta significantly induced IFN-γ immune responses. The immunogenicity after homologous vaccination with S and Alpha and heterologous vaccination with the S/Alpha candidate was better than that of the other groups, indicating the potential for developing novel DNA vaccines against different SARS-CoV-2 variants.

Copper Doping Boosts Electrocatalytic CO2 Reduction of Atomically Precise Gold Nanoclusters.

Unraveling the atomistic synergistic effects of nanoalloys on the electrocatalytic CO2 reduction reaction (eCO2RR), especially in the presence of copper, is of paramount importance. However, this endeavor encounters significant challenges due to the lack of the crystallographically determined atomic-level structure of appropriate monometallic and bimetallic analogues. Herein, we report a one-pot synthesis and structure characterization of a AuCu nanoalloy cluster catalyst, [Au15Cu4(DPPM)6Cl4(C≡CR)1]2+ (denoted as Au15Cu4). Single-crystal X-ray diffraction analysis reveals that Au15Cu4 comprises two interpenetrating incomplete, centered icosahedra (Au9Cu2 and Au8Cu3) and is protected by six DPPM, four halide, and one alkynyl ligand. The Au15Cu4 cluster and its closest monometal structural analogue, [Au18(DPPM)6Br4]2+ (denoted as Au18), as model systems, enable the elucidation of the atomistic synergistic effects of Au and Cu on eCO2RR. The results reveal that Au15Cu4 is an excellent eCO2RR catalyst in a gas diffusion electrode-based membrane electrode assembly (MEA) cell, exhibiting a high CO Faradaic efficiency (FECO) of >90%, and this efficiency is substantially higher than that of the undoped Au18 (FECO: 60% at -3.75 V). Au15Cu4 exhibits an industrial-level CO partial current density of up to -413 mA/cm2 at -3.75 V with the gas CO2-fed MEA, which is 2-fold higher than that of Au18. The density functional theory (DFT) calculations demonstrate that the synergistic effects are induced by Cu doping, where the exposed pair of AuCu dual sites was suggested for launching the eCO2RR process. Besides, DFT simulations reveal that these special dual sites synergistically coordinate a moderate shift in the d-state, thus enhancing its overall catalytic performance.

Icariin negatively regulated lipopolysaccharide-induced inflammation and ameliorated the odontogenic activity of human dental pulp cells in vitro.

Alleviating inflammation and promoting dentine regeneration is critical for the healing of pulpitis. In this study, we investigated the anti-inflammatory, angiogenesis and odontogenesis function of icariin on Human dental pulp cells (HDPCs) under inflammatory state. Furthermore, the underlying mechanisms was also evaluated. Icariin attenuated the LPS-induced pro-inflammatory marker expression, such as interleukin-1ß (IL-1ß), IL-6 and IL-8. The immunoblotting and immunofluorescence staining results showed that icariin suppressed the inflammatory responses mediated by the protein kinase B (Akt) and nuclear factor kappa-B (NF-κB) signaling cascades. Additionally, icariin also upregulated the expression of odontogenic and angiogenic genes and proteins (namely dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), anti-collagen Ⅰ (COL-Ⅰ), and vascular endothelial growth factor (VEGF) and fibroblast growth factor-1 (FGF-1)), alkaline phosphatase activity, and calcium nodule deposition in LPS-exposed HDPCs. In a word, our findings indicated that icariin attenuated pulp inflammation and promoted odontogenic and angiogenic differentiation in the inflammatory state. Icariin may be a promising vital pulp therapy agent for the regenerative treatment of the inflamed dental pulp.