Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities.

BACKGROUND: Growing evidence suggests that not only cerebrovascular disease but also Alzheimer's disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aß) and tau deposition, and WMHs through longitudinal approach. METHODS: Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aß deposition, [18F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aß or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aß or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aß or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies. RESULTS: Baseline Aß deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aß or tau deposition for 2 years. We also found a significant interaction effect between baseline Aß deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aß deposition was associated with increase of WMH volume over 2 years in female, but not in male. CONCLUSIONS: Our findings suggest that Aß deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aß increase. The results also did not support any direction of influence between tau deposition and WMHs.

Engineering of a Fluorescent Protein for a Sensing of an Intrinsically Disordered Protein through Transition in the Chromophore State.

Intrinsically disordered proteins (IDPs) not only play important roles in biological processes but are also linked with the pathogenesis of various human diseases. Specific and reliable sensing of IDPs is crucial for exploring their roles but remains elusive due to structural plasticity. Here, we present the development of a new type of fluorescent protein for the ratiometric sensing and tracking of an IDP. A ß-strand of green fluorescent protein (GFP) was truncated, and the resulting GFP was further engineered to undergo the transition in the absorption maximum upon binding of a target motif within amyloid-ß (Aß) as a model IDP through rational design and directed evolution. Spectroscopic and structural analyses of the engineered truncated GFP demonstrated that a shift in the absorption maximum is driven by the change in the chromophore state from an anionic (460 nm) state into a neutral (390 nm) state as the Aß binds, allowing a ratiometric detection of Aß. The utility of the developed GFP was shown by the efficient and specific detection of an Aß and the tracking of its conformational change and localization in astrocytes.

Clinical and genetic analyses of patients with lateralized overgrowth.

BACKGROUND: The genetic features and treatment strategies of lateralized overgrowth have been elusive. We performed this study to analyze the genetic characteristics and treatment results of propranolol- or alpelisib-treated patients with lateralized overgrowth. METHODS: Fifteen patients with lateralized overgrowth were involved. Clinical characteristics and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Targeted exome sequencing with a gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and treatment results were evaluated. The PIK3CA inhibitor alpelisib was prescribed via a managed access program. RESULTS: The identified mutations were PIK3CA (n = 7), KRAS (n = 2), PTEN (n = 1), MAP2K3 (n = 1), GNAQ (n = 1), TBC1D4 (n = 1), and TEK (n = 1). Propranolol was prescribed in 12 patients, and 7 experienced mild improvement of symptoms. Alpelisib was prescribed in two patients with a PIK3CA mutation, and the reduction of proliferated masses after 1 year of treatment was proved by WB-MRI. CONCLUSIONS: Targeted exome sequencing identified various genetic features of lateralized overgrowth. Propranolol could be applied as an adjuvant therapy for reducing vascular symptoms, but a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.

Engineered Corynebacterium glutamicum as the Platform for the Production of Aromatic Aldehydes.

Aromatic aldehydes, including 4-hydroxybenzaldehyde (4-HB aldehyde), protocatechuic (PC) aldehyde, and vanillin, are used as important flavors, fragrances, and pharmaceutical precursors and have several biological and therapeutic effects. Production of aromatic aldehydes in microbial hosts poses a challenge due to its rapid and endogenous reduction to alcohols. To address this hurdle, prospecting of the genome of Corynebacterium glutamicum yielded 27 candidate proteins that were used in comprehensive screening with a 4-hydroxybenzyl (4-HB) alcohol-producing strain. We identified that NCgl0324 has aromatic aldehyde reductase activity and contributed to 4-HB aldehyde reduction in vivo since the NCgl0324 deletion strain HB-Δ0324 produced 1.36 g/L of 4-HB aldehyde, that is, about 188% more than its parental strain. To demonstrate that NCgl0324 knockout can also improve production of PC aldehyde and vanillin, first, a basal MA303 strain that produces protocatechuate was engineered from 4-hydroxybenzoate-synthesizing C. glutamicum APS963, followed by deletion of NCgl0324 to generate PV-Δ0324. The PC aldehyde/alcohol or vanillin/vanillyl alcohol biosynthetic pathways, respectively, were able to be expanded from protocatechuate upon introduction of carboxylic acid reductase (CAR) and catechol O-methyltransferase encoded by a mutated comt m gene. In shake flask culture, the resulting NCgl0324 deletion strains PV-IΔ0324 and PV-IYΔ0324 were shown to produce 1.18 g/L PC aldehyde and 0.31 g/L vanillin, respectively. Thus, modulation of the identified NCgl0324 gene was shown to have the potential to boost production of valuable aromatic aldehydes and alcohols.

Risk of Dementia After Smoking Cessation in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Incident atrial fibrillation (AF) is associated with an increased risk of dementia. However, data on the association between smoking cessation after AF diagnosis and dementia risk are limited. Objective: To evaluate the association between changes in smoking status after AF diagnosis and dementia risk. Design, Setting, and Participants: This nationwide cohort study with 126 252 patients used data from the Korean National Health Insurance Service database, including patients who had a national health checkup examination within 2 years before and after AF diagnosis between January 1, 2010, and December 31, 2016. Based on their smoking status, participants were classified as never smokers, ex-smokers, quit smokers, and current smokers. Ex-smokers were defined as those who had quit smoking before the first examination and remained quit until the second examination. Patients who were current smokers at the first health examination but had quit smoking before the second examination were classed as quit smokers. The index date was the second health examination. Patients were followed up until dementia, death, or the study period ended (December 31, 2017), whichever occurred first. Data were analyzed from January 13, 2020, to March 29, 2022. Exposures: Smoking cessation after newly diagnosed AF. Main Outcomes and Measures: Dementia, including Alzheimer disease and vascular dementia, was the primary outcome. Cox proportional hazards regression model was used to estimate hazard ratios. Results: A total of 126 252 patients (mean [SD] age, 62.6 [12.0] years; 61.9% men) were included in the analysis. The mean (SD) CHA2DS2-VASc score, which measures the risk of ischemic stroke, was 2.7 (1.7). Smoking status of the total study population was as follows: 65 579 never smokers (51.9%), 34 670 ex-smokers (27.5%), 8919 quit smokers (7.1%), and 17 084 current smokers (13.5%). During a median of 3 years of follow-up, dementia occurred in 5925 patients (1.11 per 1000 person-years). After multivariable adjustment, the risk of quit smokers was significantly lower than that of current smokers (hazard ratio, 0.83 [95% CI, 0.72-0.95]). Conclusions and Relevance: The findings of this cohort study suggest that all types of smoking were associated with a significantly higher risk of dementia in patients with new-onset AF. Smoking cessation after AF diagnosis was associated with a lower risk of dementia than among current smokers. These findings may support promoting smoking cessation to reduce dementia risk in patients with new-onset AF.

Ten-year trends of clinical outcomes after percutaneous coronary intervention: a Korean nationwide longitudinal cohort study.

OBJECTIVES: Mortality following percutaneous coronary intervention (PCI) is a key quality measurement in clinical practice. This study investigated the 10-year trends of mortality following PCI in an unselected nationwide cohort. DESIGN: Retrospective cohort study. SETTING: A nationwide study in South Korea. PARTICIPANTS: PCI claim data from 2006 to 2015 of the National Health Insurance Service and the Statistics of Korea. MEASURES: 1-year cardiovascular or non-cardiovascular death. RESULTS: In total, 437 436 patients were included. The annual number of PCI cases increased from 32 098 to 51 990 over the decade studied (p<0.001). Patients were divided into quartile subgroups according to an estimated adjusted probability for predicting 1-year all-cause death. The proportion of patients in the high-risk quartiles increased whereas those in the low-risk quartiles decreased (p<0.001). The 1-year cumulative incidence rate of all-cause death did not change in the population with risk scores in the 1st (0.9% to 0.8%) and 2nd (1.3% to 1.3%) quartiles, whereas it increased in the population with risk scores in the 3rd (3.4% to 5.1%) and 4th (15.5% to 19.4%) quartiles (p<0.001). Compared with year 2006, the mean survival time in year 2015 was shorter by 0, 3.3 and 12.4 days in patients with risk scores in the 1st or 2nd, 3rd and 4th quartiles, respectively. These findings were also consistent for cardiovascular or non-cardiovascular deaths. CONCLUSION: The number, proportion and the overall risk of patients with a high risk for mortality after PCI increased over the decade in Korea.

Medication Adherence and Clinical Outcome of Fixed-Dose Combination vs. Free Combination of Angiotensin Receptor Blocker and Statin.

BACKGROUND: Non-compliance with angiotensin receptor blockers (ARB) or statin is one of the major hurdles to optimal medical treatment. This study investigated whether fixed-dose combination (FDC) improved compliance to medication compared with traditional free combination (FC).Methods and Results:In this retrospective nationwide cohort study, medication persistency, medication adherence measured by proportion of days covered (PDC), and all-cause death of 123,992 patients who started ARB and stain were investigated for 540 days. Patients had a mean age of 63 years and 48% were male. Persistency, PDC, and proportion of PDC ≥80% of FDC (N=34,776) were higher than those for FC (N=89,216) in both unadjusted analysis (54.5% vs. 27.8%; 84.1% vs. 63.1%; 75.5% vs. 48.1%) and propensity-score matched analysis (P<0.001, all). Death risk for the investigation period (0-540 days) was lower in FDC in unadjusted (1.8% vs. 2.6%, P<0.001) and adjusted cohort (P<0.05). In landmark analyses at days 180 and 360, there was no significant difference of death risk between FDC and FC (P>0.05). CONCLUSIONS: In this real-world data analysis, patients taking FDC of ARB and statin showed higher medication persistence and adherence compared to patients taking FC of ARB and statin up to 540 days. The risk of all-cause death was not different between FDC and FC despite better medication compliance in the FDC patients.

Ultra-flexible and rollable 2D-MoS2/Si heterojunction-based near-infrared photodetector via direct synthesis.

Atomic two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted significant attention for application in various optoelectronic devices such as image sensors, biomedical imaging systems, and consumer electronics and in diverse spectroscopic analyses. However, a complicated fabrication process, involving transfer and alignment of as-synthesized 2D layers onto flexible target substrates, hinders the development of flexible high-performance heterojunction-based photodetectors. Herein, an ultra-flexible 2D-MoS2/Si heterojunction-based photodetector is successfully fabricated through atmospheric-pressure plasma enhanced chemical vapor deposition, which enables the direct deposition of multi-layered MoS2 onto a flexible Si substrate at low temperature (<200 °C). The photodetector is responsive to near infrared light (λ = 850 nm), showing responsivity of 10.07 mA W-1 and specific detectivity (D*) of 4.53 × 1010 Jones. The measured photocurrent as a function of light intensity exhibits good linearity with a power law exponent of 0.84, indicating negligible trapping/de-trapping of photo-generated carriers at the heterojunction interface, which facilitates photocarrier collection. Furthermore, the photodetectors can be bent with a small bending radius (5 mm) and wrapped around a glass rod, showing excellent photoresponsivity under various bending radii. Hence, the device exhibits excellent flexibility, rollability, and durability under harsh bending conditions. This photodetector has significant potential for use in next-generation flexible and patchable optoelectronic devices.

Impact of medication adherence to dual antiplatelet therapy on the long-term outcome of drug-eluting or bare-metal stents.

BACKGROUND: In percutaneous coronary intervention, drug-eluting stent (DES) showed better clinical outcome compared to bare-metal stent (BMS) but mostly with different DAPT durations. HYPOTHESIS: The clinical superiority of DES over BMS may depend on the medication adherence to dual antiplatelet therapy (DAPT). METHODS: We retrospectively enrolled all Koreans PCI patients in year 2011 (n = 47,291). Medication adherence to DAPT was assessed by proportion of days covered (PDC) per 6 months. Analysis adjusted with the clinical propensity for receiving DES or BMS and DAPT PDC of the first 6 month was performed. Primary outcome was the 5-year major adverse clinical event (MACE) risk consisting all-cause death, revascularization, shock, or stroke. RESULTS: Patients with DES (n = 46,356) showed higher PDC (78% versus 60%, p<0.001) and lower MACE risk (39% versus 56%, p<0.001) compared to patients with BMS (n = 935). In the propensity-matched 1,868 patients, MACE risk was lower with DES than BMS (46% versus 54%, HR = 0.80, 95% CI = 0.70-0.91, p<0.001). In both DES and BMS, patients with good medication adherence (PDC ≥80%) showed much lower MACE risk compared to patients with PDC <80% (HR = 0.36, 95% CI = 0.30-0.44; HR = 0.40, 95%CI = 0.33-0.48, p<0.001, all). Patients with DES and PDC <80% showed higher MACE risk compared to BMS with and PDC ≥80% (HR = 1.30, 95%CI = 1.03-1.64, p = 0.027). CONCLUSIONS: Good medication adherence to DAPT in the first 6 month was prerequisite for better clinical outcome in both DES and BMS. DES with poor adherence to DAPT showed worse outcome compared with BMS with good adherence.

Computer-guided binding mode identification and affinity improvement of an LRR protein binder without structure determination.

Precise binding mode identification and subsequent affinity improvement without structure determination remain a challenge in the development of therapeutic proteins. However, relevant experimental techniques are generally quite costly, and purely computational methods have been unreliable. Here, we show that integrated computational and experimental epitope localization followed by full-atom energy minimization can yield an accurate complex model structure which ultimately enables effective affinity improvement and redesign of binding specificity. As proof-of-concept, we used a leucine-rich repeat (LRR) protein binder, called a repebody (Rb), that specifically recognizes human IgG1 (hIgG1). We performed computationally-guided identification of the Rb:hIgG1 binding mode and leveraged the resulting model to reengineer the Rb so as to significantly increase its binding affinity for hIgG1 as well as redesign its specificity toward multiple IgGs from other species. Experimental structure determination verified that our Rb:hIgG1 model closely matched the co-crystal structure. Using a benchmark of other LRR protein complexes, we further demonstrated that the present approach may be broadly applicable to proteins undergoing relatively small conformational changes upon target binding.

Structure-guided rational design of the substrate specificity and catalytic activity of an enzyme.

The quest for an enzyme with desired property is high for biocatalyic production of valuable products in industrial biotechnology. Synthetic biology and metabolic engineering also increasingly require an enzyme with unusual property in terms of substrate spectrum and catalytic activity for the construction of novel circuits and pathways. Structure-guided enzyme engineering has demonstrated a prominent utility and potential in generating such an enzyme, even though some limitations still remain. In this chapter, we present some issues regarding the implementation of the structural information to enzyme engineering, and exemplify the structure-guided rational approach to the design of an enzyme with desired functionality such as substrate specificity and catalytic efficiency.

Change of Pyogenic and Tuberculous Spondylitis between 2007 and 2016 Year : A Nationwide Study.

OBJECTIVE: We attempted to compare the incidence of pyogenic spondylitis (PS) and tuberculous spondylitis (TS) between 2007 and 2016. Furthermore, we investigated the patients who underwent surgery in 2016 compared to that in 2007. METHODS: We used a nationwide database managed by the Korean National Health Insurance Service (NHIS) in 2007 and 2016. Total 9655 patients with a newly diagnosis of PS or TS were enrolled in PS or TS group. Among them, 1721 patients underwent either fusion or decompression surgery. We analyzed demographic distribution of patients according to gender and age and year of diagnosis. RESULTS: Comparing between 2007 and 2016, the incidence of PS has increased in 2016 than in 2007 (4874 vs. 2431, p<0.0001). Conversely, declination of incidence of TS was discovered in 2016 compared to 2007 (594 vs. 1756, p<0.0001). Females showed predominance over males regarding both PS and TS (5228 vs. 4427, p<0.0001). Among them, the number of PS patients who underwent surgery increased significantly in 2016 relative to that in 2007 (979 vs. 592, p<0.0001). CONCLUSION: This nationwide study suggests that PS may increase and TS may decrease in Korea. In addition, demand for surgery regarding PS may increase.

Change in Paralytic Shellfish Toxins in the Mussel Mytilus galloprovincialis Depending on Dynamics of Harmful Alexandrium catenella (Group I) in the Geoje Coast (South Korea) during Bloom Season.

Paralytic shellfish toxins (PSTs) produced by Alexandriumcatenella (formerly A. tamarense) in Korean coastal waters caused the deaths of four people (in 1986 and 1996) who consumed contaminated mussels (Mytilus edulis). This led to more detailed consideration of the risks of PST outbreaks and incidents in Korea, including the introduction of shellfish collection bans. In this study, we investigated the relationships between A. catenella population dynamics and PST accumulation in the mussel M. galloprovincialis. Discharges from the Nakdong River affect the environmental conditions along the Geoje coast, resulting in low salinity and high nutrient levels that trigger blooms of A. catenella. At the toxin peak on 24 April 2017, the toxins detected in A. catenella cells were C1, gonyautoxin (GTX)1 and GTX2, whereas the concentrations of PSTs in M. galloprovincialis were high and in the order of GTX4 > GTX1 > GTX3 > saxitoxin (STX) > GTX2 > neoSTX > decarbamoylgonyautoxin (dcGTX)2 > dc GTX3. The PST level in mussels was also high. At 15 °C, the PSTs are constantly found to be higher (10-fold higher in 2017 and 30-fold higher in 2018) than safe levels for human consumption (80 µg STX diHCl equivalents 100 g-1).

Correction: "Changes in the medical burden of pyogenic and tuberculous spondylitis between 2007 and 2016: A nationwide cohort study".

BACKGROUND: This nationwide study aimed to compare the medical burdens of pyogenic spondylitis (PS) and tuberculous spondylitis (TS) between 2007 and 2016 in Korea. METHODS: We used a national database managed by the National Health Insurance Service (NHIS) with data from the years 2007 and 2016. A total of 9655 newly diagnosed patients with PS or TS were correspondingly enrolled in the PS or TS group. Chi square test analyses were used to compare the PS and TS groups. RESULTS: The overall incidence of infectious spondylitis during the study period was 9655 persons. The PS and TS groups consisted of 7305 and 2350 cases, respectively. Individual medical costs in the PS group (USD 10,049 ± 94 vs. USD 16,672 ± 17,729, P < 0.001) and the TS group (USD 4882 ± 6869 vs. USD 8531 ± 10,709, P < 0.001) both increased. The total medical cost for the PS group increased significantly between 2007 and 2016 in Korea (USD 24,428,560 vs. USD 81,044,196, P < 0.001). In contrast, the total medical cost for the TS group decreased between 2007 and 2016 in Korea (USD 8,573,038 vs. USD 4,879,520, P < 0.001). CONCLUSION: This nationwide study shows that the total medical cost of PS has increased and that the total medical cost of TS has decreased between 2007 and 2016 in Korea.

Changes in the medical burden of pyogenic and tuberculous spondylitis between 2007 and 2016: A nationwide cohort study.

BACKGROUND: This nationwide study aimed to compare the medical burdens of pyogenic spondylitis (PS) and tuberculous spondylitis (TS) between 2007 and 2016 in Korea. METHODS: We used a national database managed by the National Health Insurance Service (NHIS) with data from the years 2007 and 2016. A total of 9655 newly diagnosed patients with PS or TS were correspondingly enrolled in the PS or TS group. Chi square test analyses were used to compare the PS and TS groups. RESULTS: The overall incidence of infectious spondylitis during the study period was 9655 persons. The PS and TS groups consisted of 7305 and 2350 cases, respectively. Individual medical costs in the PS group (USD 10,049 ± 94 vs. USD 16,672 ± 17,729, P < 0.001) and the TS group (USD 4882 ± 6869 vs. USD 8531 ± 10,709, P < 0.001) both increased. The total medical cost for the PS group increased significantly between 2007 and 2016 in Korea (USD 24,428,560 vs. USD 81,044,196, P < 0.001). In contrast, the total medical cost for the TS group decreased between 2007 and 2016 in Korea (USD 8,573,038 vs. USD 4,879,520, P < 0.001). CONCLUSION: This nationwide study shows that the total medical cost of PS has increased and that the total medical cost of TS has decreased between 2007 and 2016 in Korea.

Enzymatic modification of daidzin using heterologously expressed amylosucrase in Bacillus subtilis.

Amylosucrases (ASase, EC 2.4.1.4) from Deinococcus geothermalis (DGAS) and Neisseria polysaccharea (NPAS) were heterologously expressed in Bacillus subtilis. While DGAS was successfully expressed, NPAS was not. Instead, NPAS was expressed in Escherichia coli. Recombinant DGAS and NPAS were purified using nickel-charged affinity chromatography and employed to modify daidzin to enhance its water solubility and bioavailability. Analyses by LC/MS revealed that the major products of transglycosylation using DGAS were daidzein diglucoside and daidzein triglucoside, whereas that obtained by NPAS was only daidzein diglucoside. The optimal bioconversion conditions for daidzein triglucoside, which was predicted to have the highest water-solubility among the daidzin derivatives, was determined to be 4% (w/v) sucrose and 250 mg/L daidzin in sodium phosphate pH 7.0, with a reaction time of 12 h. Taken together, we suggest that the yield and product specificity of isoflavone daidzin transglycosylation may be modulated by the source of ASase and reaction conditions.

Association of Congestive Heart Failure and Death with Ankylosing Spondylitis : A Nationwide Longitudinal Cohort Study in Korea.

OBJECTIVE: We attempted to discover that Ankylosing spondylitis (AS) has a comprehensive relationship with congestive heart failure and death. METHODS: We used a nationwide database managed by the Korean National Health Insurance Service from 2010 to 2014. Twelve thousand nine hundred eighty-eight patients with a diagnosis of AS and 64940 age- and sex- stratified matching subjects without AS were enrolled in the AS and control groups. Incidence probabilities of 6 years congestive heart failure and death in each group were calculated. The Cox proportional hazard regression analysis was used to estimate the hazard ratio. We divided the AS and control groups into subgroups according to sex, age, income, and comorbidities. RESULTS: During the follow-up period, 102 patients (0.79%) in the AS group and 201 patients (0.32%) in the control group developed congestive heart failure (p<0.0001). In addition, 211 (1.62%) subjects in the AS group died during the follow-up period compared to 639 (0.98%) subjects in the control group (p<0.0001). The adjusted hazard ratio of congestive heart failure and death in the AS group was 2.28 (95% confidence interval [CI], 1.80-2.89) and 1.66 (95% CI, 1.42-1.95), respectively. The hazard ratios of congestive heart failure and death were significantly increased in all of the subgroups. CONCLUSION: The incidence rates of congestive heart failure and death were increased in AS patients.

Adiponectin-Secretion-Promoting Phenylethylchromones from the Agarwood of Aquilaria malaccensis.

The therapeutic potential of adiponectin regulation has received interest because of its association with diverse human disease conditions, such as diabetes, obesity, atherosclerosis, and cancer. Phenylethylchromone derivatives from Aquilaria malaccensis-derived agarwood promoted adiponectin secretion during adipogenesis in human bone marrow mesenchymal stem cells, and 5,6-dihydroxy-2-(2-phenylethyl)chromone (1) was identified as a new chromone derivative. A target identification study with the most potent adiponectin-secretion-promoting phenylethylchromones, 6-methoxy-2-(2-phenylethyl)chromone (3) and 7-methoxy-2-(2-phenylethyl)chromone (4), showed that they are PPARγ partial agonists. Therefore, the diverse therapeutic effects of agarwood are associated with a PPARγ-mediated adiponectin-secretion-promoting mechanism.

High-efficiency enzymatic production of α-isoquercitrin glucosides by amylosucrase from Deinococcus geothermalis.

Isoquercitrin (IQ, quercetin-3-O-ß-d-glucopyranoside) has diverse biological functions, such as anti-oxidant and anti-cancer activity, but its use is limited by poor solubility and bioavailability. Enzymatically modified IQ (EMIQ) is a mixture of transglycosylated IQs that have better solubility and bioavailability than do quercetin and IQ. Two different enzymes, cyclodextrin glucanotransferase (CGTase) and amylosucrase (ASase), have the transglycosylation activity to produce EMIQ. Both enzymes produce a variety of EMIQs including IQ, IQ-glucoside (IQ-G1), IQ-diglucoside (IQ-G2), and IQ-triglucoside (IQ-G3). ASase had a higher bioconversion yield from IQ to EMIQ (97.6%) than did CGTase (76.8%). In addition, the yield of IQ-G3, which was the most bioavailable form, was higher with ASase (46%) than with CGTases (8%). Taken together, these results suggest that ASase can be used to synthesize EMIQ in a simple and specific process.