Magnolia kobus Extract Inhibits Periodontitis-Inducing Mediators in Porphyromonas gingivalis Lipopolysaccharide-Activated RAW 264.7 Cells.

Periodontitis, a disease caused by inflammation of oral bacteria, contributes to the loss of alveolar bone and destruction of connective tissues. Porphyromonas gingivalis, a Gram-negative bacterium, is known to possess important pathogenic factors for periodontal disease. In this study, we investigated the anti-periodontitis effects of Magnolia kobus extract (MKE) and magnolin as a component of Magnolia kobus (MK) in murine macrophage RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Effects of MKE and magnolin on the mechanism of RAW 264.7 cellular inflammation were determined by analyzing nitric oxide (NO) production and Western blot protein expression (n = 3). MKE/magnolin inhibited NO production without affecting cell survival. MKE/magnolin treatment inhibited LPS-induced pro-inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs such as MMP-1, 3, 8, 9, and 13), and protein levels of inflammatory mediators (such as TNF-α, IL-1ß, and mPGES-1). MKE/magnolin also suppressed NF-κB activation by inhibiting the TLR4 signaling pathway. These findings suggest that MKE has a therapeutic effect on inflammatory periodontal disease caused by oral bacterium P. gingivalis and that magnolin is a major functional component in the anti-inflammatory effect of MKE.

Chemical Profiles and Antiobesity Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract in High Fat Diet Fed Mice.

The present study aimed to evaluate the antiobesity potential and synergistic effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extracts, in HFD-induced obese mice. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD + AM, HFD + LE or HFD + ALM16 (50, 100, and 200 mg/kg) daily for 5 weeks. Compared to the ND group, HFD-fed mice showed significant increases in body weight, food efficiency ratio, weights of white adipose tissues, adipocytes size, liver weight, and hepatic steatosis grade. However, ALM16 significantly reduced those increases induced by HFD. Moreover, as compared to the HFD group, the ALM16 group significantly ameliorated serum levels of lipid profiles (TG, TC, HDL, and LDL), adipokines (leptin and adiponectin), and liver damage markers (AST and ALT levels). Notably, ALM16 was more effective than AM or LE alone and had a similar or more potent effect than Garcinia cambogia extracts, as a positive control, at the same dose. These results demonstrate that ALM16 synergistically exerts anti-obesity effects based on complementary interactions between each component. Also, metabolic profiling between each extract and the ALM16 was confirmed by UPLC-QTOF/MS, and the difference was confirmed by relative quantification.

Distribution of Corynebacterium Species and Comparative Results of Diagnostic Methods for Identifying Corynebacterium in Experimental Mice in Korea.

The genus Corynebacterium, composed of Gram-positive diphtheroid rod-shaped bacteria, induces severe diseases, such as Corynebacterium-associated hyperkeratosis and pseudotuberculosis, in immunodeficient mice. We isolated and identified a total of 165 strains of Corynebacterium species from experimental mice in Korean laboratories, diagnosed using several methods. When identified based on molecular methods, namely, 16S rRNA and rpoB gene sequence analysis, the main Corynebacterium species isolated in Korean laboratory mice were C. mastitidis (44.8%, n = 74), C. bovis (25.5%, n = 42), C. lowii (21.2%, n = 35), and C. amycolatum (8.5%, n = 14). Diagnoses were also performed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and biochemical methods. MALDI-TOF MS yielded results that were 77.9% identical to the molecular identification results, whereas biochemical methods showed only 15.5% identical to molecular identification, partly owing to difficulties in distinguishing among C. mastitidis strains. Collectively, our findings indicate that molecular biological methods are better suited for detecting and identifying Corynebacterium species candidates isolated from mice than biochemical methods. Because of limitations associated with the use of MALDI-TOF MS, more precise results will be obtained by complementing this approach with other methods when used for rapid identification testing.

Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications.

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Deciphering the key factors determining spatio-temporal heterogeneity of cyanobacterial bloom dynamics in the Nakdong River with consecutive large weirs.

Following the construction of eight large weirs in a 200-km section of the Nakdong River, which is a major water source for the region, harmful cyanobacterial blooms have been occurring annually, causing severe problems with water quality. The present study investigated the community structure of harmful cyanobacteria and identified temporal and spatial patterns in harmful cyanobacterial blooms and their dynamic relationships with physicochemical, hydrological, and meteorological variables in the eight weir sections for 6 years from 2013 to 2018. The dominant harmful cyanobacteria in the eight weir sections were Aphanizomenon and Microcystis spp. There was a successional phenomenon wherein Aphanizomenon spp. first bloomed in spring, and then Microcystis spp. bloomed as water temperatures increased. Additionally, the initiation and duration of the blooms of both genera were affected by the timing and volume of heavy rainfall that caused flushing of cyanobacterial biomass, resulting in direct reduction of cyanobacterial growth in all sections. The harmful cyanobacteria of upstream weirs did not affect the biomass of downstream weirs in terms of either growth initiation or time taken to reach peak biomass, despite being physically connected. Owing to the long retention time during the dry season, similar to what occurs in separate reservoirs, the water quality of each weir section, particularly regarding nutrient characteristics and retention time, were the major factors determining the harmful cyanobacterial abundance, resulting in heterogeneous spatial distribution of harmful cyanobacterial blooms in the Nakdong River.

Nitrogen Stimulates Microcystis-Dominated Blooms More than Phosphorus in River Conditions That Favor Non-Nitrogen-Fixing Genera.

Despite the implementation of intensive phosphorus reduction measures, periodic outbreaks of cyanobacterial blooms in large rivers remain a problem in Korea, raising the need for more effective solutions to reduce their occurrence. This study sought to evaluate whether phosphorus or nitrogen limitation is an effective approach to control cyanobacterial (Microcystis) blooms in river conditions that favor this non-nitrogen-fixing genus. These conditions include nutrient enrichment, high water temperature, and thermal stratification during summer. Mesocosm bioassays were conducted to investigate the limiting factors for cyanobacterial blooms in a river reach where severe Microcystis blooms occur annually. We evaluated the effect of five different nitrogen (3, 6, 9, 12, and 15 mg/L) and phosphorus (0.01, 0.02, 0.05, 0.1, and 0.2 mg/L) concentrations on algae growth. The results indicate that nitrogen treatments stimulated cyanobacteria (mostly Microcystis aeruginosa) more than phosphorus. Interestingly, phosphorus additions did not stimulate cyanobacteria, although it did stimulate Chlorophyceae and Bacillariophyceae. We conclude that phosphorus reduction might have suppressed the growth of Chlorophyceae and Bacillariophyceae more than that of cyanobacteria; therefore, nitrogen or at least both nitrogen and phosphorus control appears more effective than phosphorus reductions alone for reducing cyanobacteria in river conditions that are favorable for non-nitrogen-fixing genera.

Cellular Response of Ventricular-Subventricular Neural Progenitor/Stem Cells to Neonatal Hypoxic-Ischemic Brain Injury and Their Enhanced Neurogenesis.

PURPOSE: To elucidate the brain's intrinsic response to injury, we tracked the response of neural stem/progenitor cells (NSPCs) located in ventricular-subventricular zone (V-SVZ) to hypoxic-ischemic brain injury (HI). We also evaluated whether transduction of V-SVZ NSPCs with neurogenic factor NeuroD1 could enhance their neurogenesis in HI. MATERIALS AND METHODS: Unilateral HI was induced in ICR neonatal mice. To label proliferative V-SVZ NSPCs in response to HI, bromodeoxyuridine (BrdU) and retroviral particles encoding LacZ or NeuroD1/GFP were injected. The cellular responses of NSPCs were analyzed by immunohistochemistry. RESULTS: Unilateral HI increased the number of BrdU+ newly-born cells in the V-SVZ ipsilateral to the lesion while injury reduced the number of newly-born cells reaching the ipsilateral olfactory bulb, which is the programmed destination of migratory V-SVZ NSPCs in the intact brain. These newly-born cells were directed from this pathway towards the lesions. HI significantly increased the number of newly-born cells in the cortex and striatum by the altered migration of V-SVZ cells. Many of these newly-born cells differentiated into active neurons and glia. LacZ-expressing V-SVZ NSPCs also showed extensive migration towards the non-neurogenic regions ipsilateral to the lesion, and expressed the neuronal marker NeuN. NeuroD1+/GFP+ V-SVZ NSPCs almost differentiated into neurons in the peri-infarct regions. CONCLUSION: HI promotes the establishment of a substantial number of new neurons in non-neurogenic regions, suggesting intrinsic repair mechanisms of the brain, by controlling the behavior of endogenous NSPCs. The activation of NeuroD1 expression may improve the therapeutic potential of endogenous NSPCs by increasing their neuronal differentiation in HI.

Impact of intraoperative zero-balance fluid therapy on the occurrence of acute kidney injury in patients who had undergone colorectal cancer resection within an enhanced recovery after surgery protocol: a propensity score matching analysis.

PURPOSE: An enhanced recovery after surgery (ERAS) protocol for colorectal cancer resection encourages perioperative euvolemic status, and zero-balance fluid therapy is recommended for low-risk patients. Recently, several studies have reported concerns of increased acute kidney injury (AKI) in patients within an ERAS protocol. In the present study, we investigated the impact of intraoperative zero-balance fluid therapy within an ERAS protocol on postoperative AKI. METHODS: Patients who underwent elective surgery for primary colorectal cancer were divided into zero-balance and non-zero-balance fluid therapy groups according to intraoperative fluid amount and balance. After propensity score (PS) matching, 210 patients from each group were selected. Incidences of AKI were compared between the two groups according to the Kidney Disease Improving Global Outcomes criteria. Postoperative kidney functions and surgical outcomes were also compared. RESULTS: AKI was significantly higher in the zero-balance fluid therapy group compared to the non-zero-balance fluid therapy group (21.4% vs. 13.8%, p = 0.040) in PS-matched patients. The decrease in the estimated glomerular filtration rate on the day of surgery was significantly higher in the zero-balance fluid therapy group (- 5.9 mL/min/1.73 m2 vs. - 1.4 mL/min/1.73 m2, p = 0.005). There were no differences in general morbidity or mortality rate, although surgery-related complications were more common in the zero-balance group. CONCLUSIONS: Despite the proven benefits of zero-balance fluid therapy in colorectal ERAS protocols, care should be taken to monitor for postoperative AKI. Further studies regarding the clinical significance of postoperative AKI occurrence and optimised intraoperative fluid therapy are needed in a colorectal ERAS setting.

Comparison between Post-Operative Analgesic Efficacy of Low-Concentration High-Volume and High-Concentration Low-Volume Combinations of Ropivacaine for Transverse Abdominis Plane Block in Pediatric Open Inguinal Hernia Repair.

Transverse abdominis plane (TAP) block can provide post-operative analgesia in children undergoing open inguinal hernia repair. However, the optimal anesthetic dose, and concentration for TAP block in the pediatric population, is not well defined. This study compared the post-operative analgesic effect of TAP block between low-concentration, with high-volume (LCHV) and high-concentration, with low-volume (HCLV) combinations of local anesthetic. Forty-four patients who underwent open inguinal hernia repair were randomly assigned to two groups. The patients in the LCHV group received 0.67 mL/kg of 0.15% ropivacaine. Whereas, those in the HCLV group received 0.4 mL/kg of 0.25% ropivacaine. Both groups received the same amount of ropivacaine (1 mg/kg). The primary outcome measure was the face, leg, activity, cry, consolability (FLACC) scale score at post-anesthetic care unit (PACU; T1). FLACC scale score at T1 was significantly lower in the HCLV group (2.91 versus 1.43; mean difference, -1.49; 95% confidence interval, -0.0245 to -2.936; p = 0.0464). FLACC scale scores one hour and six hours after the surgery were not different between the two groups. This study reports better post-operative analgesic effects after unilateral open inguinal hernia repair with 1 mg/kg of 0.25% ropivacaine than 1 mg/kg of 0.15% ropivacaine at PACU.

[Development of an Aging Anxiety Scale for Middle-Aged Women].

PURPOSE: This was a methodological study that aimed to develop a measurement scale for aging anxiety among middle-aged women. METHODS: In this study, construct factors were extracted, and a conceptual framework was established through an extensive literature review and in-depth interviews with middle-aged women. Under the conceptual framework, 44 preliminary items were constructed, and a preliminary scale of 25 items was completed after two rounds of expert validation and item review. For this study, data were collected from 201 women aged 40~59 years, and the construct validity and reliability of the preliminary scale were verified. RESULTS: To verify the construct validity, exploratory factor analysis was conducted. Four factors containing 19 items were extracted. Concurrent validity of the developed scale was verified with Pearson's correlation analysis. The final scale comprised 4 factors ("Social valueless", "Physical weakness", "Concern about changes in appearance", and "Expectations of old age") and 19 items. The Cronbach's α value was .91. CONCLUSION: The scale for measuring aging anxiety in middle-aged women developed in this study validly reflected the peculiarities of aging anxiety in middle-aged women, who experience many physical, emotional, and social changes. The scale can be said to reflect the cultural background, as it reflected real experiences gained through in-depth interviews with middle-aged women.

Effects of Weir Construction on Phytoplankton Assemblages and Water Quality in a Large River System.

Flow regulation is one of the most common anthropogenic factors affecting rivers worldwide. In Korea, 16 weirs were constructed along four major rivers from 2009 to 2012. This study aimed to elucidate initial changes in physical, chemical, and biological variables after the construction of consecutive weirs on the Nakdong River, a major large river system. Water quality variables and phytoplankton cell densities were investigated at eight representative sites and compared with the data recorded before the weir construction. There were spatial and temporal changes in the hydraulic retention time (HRT), total phosphorus (TP), and chlorophyll a concentrations among the eight weir sections. HRT increased after the weir construction, while TP and chlorophyll a tended to decrease from the middle to lower section of the Nakdong River. Furthermore, differences were observed in the phytoplankton community composition between 2006⁻2007 and 2013. There was a marginal decrease in the duration of centric diatom (Stephanodiscus hantzschii) blooms after weir construction. However, Microcystis aeruginosa proliferated more extensively during summer and autumn than it did before the weir construction. Our results suggest that changes in hydrological factors, in response to consecutive weir construction, may contribute to greater physical, chemical, and ecological variability.

Molecular Verification of Bloom-forming Aphanizomenon flos-aquae and Their Secondary Metabolites in the Nakdong River.

Aphanizomenon spp. have formed harmful cyanobacterial blooms in the Nakdong River during spring, autumn, and now in winter, and the expansion of blooming period and area, associated with the global warming is predicted. The genus Aphanizomenon has been described to produce harmful secondary metabolites such as off-flavors and cyanotoxins. Therefore, the production of harmful secondary metabolites from the Aphanizomenon blooms in the Nakdong River needs to be monitored to minimize the risk to both water quality and public health. Here, we sampled the cyanobacterial blooms in the Nakdong River and isolated ten Aphanizomenon strains, morphologically classified as Aphanizomenon flos-aquae Ralfs ex Bornet et Flahault 1888. Phylogenetic analysis using 16S rRNA and internal transcribed spacer (ITS) region nucleotide sequences confirmed this classification. We further verified the harmful secondary metabolites-producing potential of A. flos-aquae isolates and water samples containing cyanobacterial blooms using PCR with specific primer sets for genes involved in biosynthesis of off-flavor metabolites (geosmin) and toxins (microcystins, saxitoxins and cylindrospermopsins). It was confirmed that these metabolite biosynthesis genes were not identified in all isolates and water samples containing only Aphanizomenon spp. Thus, it is likely that there is a low potential for the production of off-flavor metabolites and cyanotoxins in Aphanizomenon blooms in the Nakdong River.

LRRK2 Kinase Activity Induces Mitochondrial Fission in Microglia via Drp1 and Modulates Neuroinflammation.

Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase domain and G2019S, the most prevalent LRRK2 pathogenic mutation, increases its kinase activity. LRRK2 regulates mitochondria morphology and autophagy in neurons. LPS treatment increases LRRK2 protein level and mitochondrial fission in microglia, and down-regulation of LRRK2 expression or inhibition of its kinase activity attenuates microglia activation. Here, we evaluated the direct role of LRRK2 G2019S in mitochondrial dynamics in microglia. Initial observation of microglia in G2019S transgenic mice revealed a decrease in mitochondrial area and shortage of microglial processes compared with their littermates. Next, we elucidated the molecular mechanisms of these phenotypes. Treatment of BV2 cells and primary microglia with LPS enhanced mitochondrial fission and increased Drp1, a mitochondrial fission marker, as previously reported. Importantly, both phenotypes were rescued by treatment with GSK2578215A, a LRRK2 kinase inhibitor. Finally, the protein levels of CD68, an active microglia marker, Drp1 and TNF-α were significantly higher in brain lysates of G2019S transgenic mice compared with the levels in their littermates. Taken together, our data suggest that LRRK2 could promote microglial mitochondrial alteration via Drp1 in a kinase-dependent manner, resulting in stimulation of pro-inflammatory responses. This mechanism in microglia might be a potential target to develop PD therapy since neuroinflammation by active microglia is a major symptom of PD.

Brain and spinal cord injury repair by implantation of human neural progenitor cells seeded onto polymer scaffolds.

Hypoxic-ischemic (HI) brain injury and spinal cord injury (SCI) lead to extensive tissue loss and axonal degeneration. The combined application of the polymer scaffold and neural progenitor cells (NPCs) has been reported to enhance neural repair, protection and regeneration through multiple modes of action following neural injury. This study investigated the reparative ability and therapeutic potentials of biological bridges composed of human fetal brain-derived NPCs seeded upon poly(glycolic acid)-based scaffold implanted into the infarction cavity of a neonatal HI brain injury or the hemisection cavity in an adult SCI. Implantation of human NPC (hNPC)-scaffold complex reduced the lesion volume, induced survival, engraftment, and differentiation of grafted cells, increased neovascularization, inhibited glial scar formation, altered the microglial/macrophage response, promoted neurite outgrowth and axonal extension within the lesion site, and facilitated the connection of damaged neural circuits. Tract tracing demonstrated that hNPC-scaffold grafts appear to reform the connections between neurons and their targets in both cerebral hemispheres in HI brain injury and protect some injured corticospinal fibers in SCI. Finally, the hNPC-scaffold complex grafts significantly improved motosensory function and attenuated neuropathic pain over that of the controls. These findings suggest that, with further investigation, this optimized multidisciplinary approach of combining hNPCs with biomaterial scaffolds provides a more versatile treatment for brain injury and SCI.

Neurogenin-2-transduced human neural progenitor cells attenuate neonatal hypoxic-ischemic brain injury.

Neonatal hypoxic-ischemic (HI) brain injury leads to high mortality and neurodevelopmental disabilities. Multipotent neural progenitor cells (NPCs) with self-renewing capacity have the potential to reduce neuronal loss and improve the compromised environment in the HI brain injury. However, the therapeutic efficacy of neuronal-committed progenitor cells and the underlying mechanisms of recovery are not yet fully understood. Therefore, this study investigated the regenerative ability and action mechanisms of neuronally committed human NPCs (hNPCs) transduced with neurogenin-2 (NEUROG2) in neonatal HI brain injury. NEUROG2- or green fluorescent protein (GFP)-encoding adenoviral vector-transduced hNPCs (NEUROG2- or GFP-NPCs) were transplanted into neonatal mouse brains with HI injury. Grafted NEUROG2-NPCs showed robust dispersion and engraftment, prolonged survival, and neuronal differentiation in HI brain injury. NEUROG2-NPCs significantly improved neurological behaviors, decreased cellular apoptosis, and increased the neurite outgrowth and axonal sprouting in HI brain injury. In contrast, GFP-NPC grafts moderately enhanced axonal extension with limited behavioral recovery. Notably, NEUROG2-NPCs showed increased secretion of multiple factors, such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NTF3), fibroblast growth factor 9 (FGF9), ciliary neurotrophic factor (CNTF), and thrombospondins 1 and 2 (THBS 1/2), which promoted SH-SY5Y neuroblastoma cell survival and neurite outgrowth. Thus, we postulate that NEUROG2-expressing human NPCs facilitate functional recovery after neonatal HI brain injury via their ability to secrete multiple factors that enhance neuronal survival and neuroplasticity.

Acidification of stratum corneum prevents the progression from atopic dermatitis to respiratory allergy.

The presence of congenitally impaired skin barrier followed by atopic dermatitis (AD) is an initial step in the atopic march. The maintenance of acidic pH in the stratum corneum (SC) has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. To determine whether an AD murine model, flaky tail mice, with inherited filaggrin deficiency could develop airway inflammation by repeated topical application followed by nasal inhalation of house dust mite (HDM) antigen (defined as a novel "atopic march animal model"), and whether maintenance of an acidic SC environment by continuous application of acidic cream could interrupt the following atopic march. During the course of HDM treatment, acidic cream (pH2.8) or neutral cream (pH7.4) was applied to flaky tail mice twice daily. Repeated applications and inhalations of HDM to flaky tail mice induced AD skin lesions followed by respiratory allergies. Maintenance of SC acidity inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. Collectively, a novel atopic march model could be developed by repeated epicutaneous and nasal applications of HDM to flaky tail mice, and that the acidification of SC could prevent the atopic march from AD to respiratory allergy.

Application of Topical Acids Improves Atopic Dermatitis in Murine Model by Enhancement of Skin Barrier Functions Regardless of the Origin of Acids.

BACKGROUND: The acidic pH of the stratum corneum (SC) is important for epidermal permeability barrier homeostasis. Acidification of the skin surface has been suggested as a therapeutic strategy for skin disorders such as atopic dermatitis (AD). OBJECTIVE: We performed an animal study to evaluate the usefulness of acidification of SC for inhibition of AD lesions and to find out if the therapeutic effect of vinegar is attributable to its herbal contents, rather than its acidity. METHODS: Five groups of six oxazolone-treated (Ox)-AD mice were treated for three weeks with creams of different acidity: vehicle cream alone (pH 5.5), neutralized vinegar cream (pH 7.4), pH 5.0 vinegar cream, pH 3.5 vinegar cream, and pH 3.5 hydrogen chloride (HCl) cream. Also, we have compared two groups of Ox-AD mice treated with pH 5.5 vehicle cream or pH 5.5 vinegar cream. RESULTS: Ox-AD mice treated with acidic creams exhibited fewer AD-like lesions, had significantly lower eczema scores, decreased basal by transepidermal water loss (TEWL), and increased SC hydration compared to the groups given only vehicle and neutral cream. There was no significant difference between the acidic vinegar and HCl groups. Between the groups treated with vehicle and pH 5.5 vinegar cream, there was no difference in eczema score, basal TEWL and SC hydration. CONCLUSION: Application of topical acids, regardless of their source materials, inhibits the development of AD lesions by maintenance of skin surface pH and skin barrier function in murine model.

Korea Brain Initiative: Integration and Control of Brain Functions.

This article introduces the history and the long-term goals of the Korea Brain Initiative, which is centered on deciphering the brain functions and mechanisms that mediate the integration and control of brain functions that underlie decision-making. The goal of this initiative is the mapping of a functional connectome with searchable, multi-dimensional, and information-integrated features. The project also includes the development of novel technologies and neuro-tools for integrated brain mapping. Beyond the scientific goals this grand endeavor will ultimately have socioeconomic ramifications that not only facilitate global collaboration in the neuroscience community, but also develop various brain science-related industrial and medical innovations.