Preclinical evaluation of general toxicity and safety pharmacology of a receptor-binding domain-based COVID-19 subunit vaccine in various animal models.

The coronavirus disease 2019 pandemic has resulted in the introduction of several naïve methods of vaccine development, which have been used to prepare novel viral vectors and mRNA-based vaccines. However, reluctance to receive vaccines owing to the uncertainty regarding their safety is prevalent. Therefore, rigorous safety evaluation of vaccines through preclinical toxicity studies is critical to determine the safety profiles of vaccine candidates. This study aimed to evaluate the toxicity profile of HuVac-19, a subunit vaccine of SARS-CoV-2 utilizing the receptor-binding domain as an antigen, in rats, rabbits, and dogs using single- and repeat-dose study designs. Repeat-dose toxicity studies in rats and rabbits showed transient changes in hematological and serum biochemical parameters in the adjuvant and/or vaccine groups; however, these changes were reversed or potentially reversible after the recovery period. Moreover, temporary reversible changes in absolute and relative organ weights were observed in the prostate of rats and the thymus of rabbits. Gross examination of the injection sites in rats and rabbits treated with the adjuvant- and HuVac-19 showed discoloration and foci, whereas histopathological examination showed granulomatous inflammation, inflammatory cell infiltration, and myofiber degeneration/necrosis. This inflammatory response was local, unassociated with other toxicological changes, and resolved. In a pharmacological safety study, no toxicological or physiological changes associated with HuVac-19 administration were observed. In conclusion, HuVac-19 was not associated with any major systemic adverse effects in the general toxicity and safety pharmacology evaluation, demonstrating that HuVac-19 is a vaccine candidate with sufficient capacity to be used in human clinical trials.

An Hetero-Epitaxially Grown Zeolite Membrane.

The secondary growth methodology to form zeolite membranes has stringent requirements for homogeneous epitaxial intergrowth of the seed layer and limits the number of accessible high-quality zeolite membranes. Despite previous reports on hetero-epitaxial growth, high-performance zeolite membranes have yet to be reported using this approach. Here, the successful hetero-epitaxial growth of highly siliceous ZSM-58 (DDR-type zeolite) films from a SSZ-13 (CHA-type zeolite) seed layer is reported. The resulting membranes show excellent CO2 perm-selectivities, having maximum CO2 /N2 and CO2 /CH4 separation factors (SFs) as high as about 17 and 279, respectively, at 30 °C. Furthermore, the hybrid membrane maintains the CO2 perm-selectivity in the presence of water vapor (the third main component in both cases), that is, CO2 /N2 SF of about 14 and CO2 /CH4 SF of about 78, respectively, at 50 °C (a representative temperature of both CO2 -containing streams).

PREDICTION OF NONDIAGNOSTIC RESULTS IN FINE-NEEDLE ASPIRATION OF THYROID NODULES: UTILITY OF ON-SITE GROSS VISUAL ASSESSMENT OF SPECIMENS FOR LIQUID-BASED CYTOLOGY.

OBJECTIVE: To explore a comprehensive approach for on-site gross visual assessments of liquid-based cytology (LBC) specimens of thyroid nodules and determine morphologic criteria that help predict nondiagnostic rates. METHODS: Two-hundred nodules from 165 patients who underwent fine-needle aspiration (FNA) at our hospital were included in this prospectively designed, retrospective analysis. Specimens were visually assessed on-site for three morphologic categories (specimen color, specimen volume, and particle count) using a 5-point grading. RESULTS: Twenty-two nodules (11%) showed nondiagnostic results. Regarding specimen color, nondiagnostic rates tended to be higher in grades 1 (75%) and 5 (100%) than in grades 2 (18%), 3 (8%), or 4 (17%), with a significant difference between grade 1 and grade 3 ( P = .003). For specimen volume, nondiagnostic results were significantly more common in grade 1 (33%) and 5 (33%) than in grades 3 (5%) or 4 (1%) ( P<.005). There was a significant negative correlation between the grading of the particle count and the nondiagnostic rate (Spearman ρ = -1.000; P<.001). The sensitivity and specificity in the prediction of nondiagnostic results were 77% and 76%, respectively, at the optimal cutoff value of 2 (grade 2 or lower). CONCLUSION: Particle count was an important morphologic criterion that helped predict nondiagnostic rates in LBC specimens of thyroid nodules, and the specimen color and volume were also useful adjuncts. In routine practice, on-site gross visual assessment followed by resampling (if necessary) may potentially help reduce the rates of nondiagnostic results, repeat FNAs, and the number of unnecessary needle passes. ABBREVIATIONS: FNA = fine-needle aspiration; LBC = liquid-based cytology; ROC = receiver operating characteristic; US = ultrasonography.

Gender- and age-group-specific associations between physical performance and bone mineral density, falls, and osteoporotic fractures in Koreans: the Chungju Metabolic Disease Cohort study.

Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling.

Higher adherence to a Mediterranean-type diet is associated with reduced psychosocial stress levels in baby boomers: a cross-sectional study.

BACKGROUND/OBJECTIVES: This study investigated the relationship between adherence to the Mediterranean diet among Korean baby boomers and their levels of psychosocial stress. SUBJECTS/METHODS: The study included 1,656 adults (889 men and 797 women) born between 1955 and 1963 who participated in the 2005-2006 survey of the community-based Korean Genome and Epidemiology Study (KoGES). The Mediterranean-type diet score (MTDS) was calculated from the semi-quantitative food frequency questionnaire (SQFFQ) data. The psychosocial stress levels were calculated using the psychosocial well-being index-short form (PWI-SF). Logistic regression analyses were performed to analyze the association between the MTDS (tertiles) and the prevalence of high psychosocial stress by gender. RESULTS: The ranges of the MTDS tertile groups were T1 (20-33 points), T2 (34-37 points), and T3 (38-39 points) for men, T1 (20-33 points), T2 (34-37 points), and T3 (38-48 points) for women. In both men and women, the consumption of whole grains, potatoes, fruits, vegetables, legumes, and fish increased with higher MTDS, while the consumption of red meat and dairy products decreased (P for trend < 0.05). As MTDS score increased the intake of energy, fiber, vitamins, and minerals (P for trend < 0.05). Men in the highest MTDS tertile had a 41% lower odds ratio (OR) of high psychosocial stress compared with those in the lowest tertile (OR, 0.59; 95% confidence interval [CI], 0.38-0.91). Similarly, women in the highest tertile of the MTDS had a 39% lower OR of high psychosocial stress compared with those in the lowest tertile (OR, 0.61; 95% CI, 0.40-0.95). CONCLUSION: Promoting adherence to the Mediterranean diet among baby boomers may have a positive impact on reducing their levels of psychosocial stress.

H1N1 nanobody development and therapeutic efficacy verification in H1N1-challenged mice.

Influenza A virus causes numerous deaths and infections worldwide annually. Therefore, we have considered nanobodies as a potential treatment for patients with severe cases of influenza. We developed a nanobody that was expected to have protective efficacy against the A/California/04/2009 (CA/04; pandemic 2009 flu strain) and evaluated its therapeutic efficacy against CA/04 in mice experiments. This nanobody was derived from the immunization of the alpaca, and the inactivated CA/04 virus was used as an immunogen. We successfully generated a nanobody library through bio-panning, phage ELISA, and Bio-layer interferometry. Moreover, we confirmed that administering nanobodies after lethal doses of CA/04 reduced viral replication in the lungs and influenza-induced clinical signs in mice. These research findings will help to develop nanobodies as viral therapeutics for CA/04 and other infectious viruses.

Antibiotic resistance in bacteria isolated from freshwater aquacultures and prediction of the persistence and toxicity of antimicrobials in the aquatic environment.

The occurrence of antibiotic-resistant bacteria isolated from freshwater aquaculture effluents was investigated. The bacterial strains were collected from four different freshwater aquaculture effluents (catfish, trout, eel, and loach). Based on sequence of 16S rRNA, a total of 20 bacterial strains was isolated and one half of the isolated bacteria were Aeromonas sp. The antimicrobial sensitivity test was performed using the disc diffusion method. Individual antibiotic-resistant bacteria to antimicrobials were 41.7% and multiple antibiotic resistant bacteria were 58.3%. The disinfection of antibiotic-resistant bacteria by electron beam (E-beam) irradiation was carried out using an electron accelerator. Antibiotic-resistant bacteria were effectively disinfected by E-beam irradiation. The isolated bacteria were completely disinfected at a dose of less than 2 kGy. The persistence and toxicity of each antimicrobial in the aquatic environment was estimated due to the human health and ecosystems. In order to estimate the persistence and toxicity of antimicrobials in the aquatic environment, two quantitative structure activity relationship (QSAR) models were used. The persistence and toxicity of each antimicrobial were influenced on its hydrophobicity. In addition, QSAR models showed that isoelectric point and hydrogen bonding acceptor are key parameters to estimate the persistence and toxicity of antimicrobials in the aquatic environment.

Sodium intake trend and current intake level by meal provision place among the citizens of Seoul.

BACKGROUND/OBJECTIVES: The diversity of meal provision places has increased in recent years and sodium intake can vary depending on where meals are eaten, particularly in large cities. In this study, an analysis of the recent trends in sodium intake was performed and a comparison of sodium intake level according to meal provision place among citizens of Seoul was performed. SUBJECTS/METHODS: Data from a 24-h recall dietary intake survey from the 2010-2019 Korea National Health and Nutrition Examination Survey (KNHANES) were used in order to determine the trends in sodium intake among citizens of Seoul, aged 3-74 years old. (n = 11,811). The trend of daily sodium intake was presented in absolute amount and proportion compared to the chronic disease risk reduction intake (CDRR) for each selected characteristic. A comparison of sodium intake level according to meal provision place by sex and age groups as a total amount per meal (mg), density per meal (mg/1,000 kcal), and proportion of the daily sodium intake was performed using the 2016-2019 KNHANES. RESULTS: Sodium intake levels showed a downward trend from 2010-2019. The highest level of sodium intake was observed for subjects aged 30-49, and the level for males aged 30-49 was 202.8% higher than the CDRR. Results of the analysis of sodium intake per meal according to meal provision place showed that the highest sodium intake was in the order of restaurant meal (RM) > institutional foodservice (IF) > home meal (HM) > convenience food (CF). A higher sodium density (mg/1,000 kcal) was observed for IF compared with RM in most adults. Adults aged over 50 years old consumed more than half of the daily sodium in HM. CONCLUSION: Significant variation in the level of sodium intake was observed according to sex and age groups, therefore, different approaches and nutrition policies based on meal provision place are needed.

Relationship between vitamin D, parathyroid hormone, and bone mineral density in elderly Koreans.

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.

Comparison of physicochemical characteristics and consumer perception of rice samples with different countries of origin and prices.

BACKGROUND: Rice is the only food item which is not liberalized in Korea. To prepare for future liberalization of the rice market in Korea, the physicochemical characteristics and consumer perception of four domestic rice samples were compared with those of 11 foreign rice samples. Additionally, the influences of country of origin (CO) and price on purchase intent (PI) and willingness to pay (WTP) were investigated. RESULTS: Consumer acceptance of rice samples from Japan was generally higher than that of rice samples from other countries. In an informed test, PI was affected by price and CO, while WTP was affected mostly by price. The PI decreased with the price provided while the WTP increased. In a blind test, consumers evaluated PI and WTP according to sensory liking. The PI was higher in the informed test than in the blind test in all domestic samples. Generally, consumer acceptance was highly correlated with fat acidity (r = - 0.76), protein content (r = - 0.72), and b value (r = - 0.64) of the rice samples. CONCLUSION: Further efforts to increase the quality of rice are recommended for survival in the global market after liberalization of rice, even though consumers showed loyalty for PI of domestic samples.

Evaluation of a Brief Sleep Intervention Designed to Improve the Sleep, Mood, and Cognitive Performance of Esports Athletes.

This study evaluated a brief sleep intervention designed to improve the sleep, mood, and cognitive performance of professional electronic sports (esports) athletes from three major esports regions (i.e., Asia, North America, and Oceania). Fifty-six esports athletes from South Korea (N = 34), the United States (N = 7), and Australia (N = 15) completed the study. Participants completed an initial 2-week pre-intervention phase to establish a baseline, followed by a 2-week intervention phase that involved a group sleep education class, 1:1 session with a trained clinical psychologist, and daily biofeedback. A wrist activity monitor and daily sleep diary were used to monitor sleep during both phases, while at pre- and post-intervention, participants completed a battery of sleep and mood questionnaires and underwent cognitive performance testing. Sleep knowledge increased from pre- to post-intervention (d = 0.83 [95% CI −1.21, −0.43], p =< 0.001), while there were modest improvements in sleep diary estimates (i.e., sleep onset latency (Mdiff = −2.9 min, p = 0.02), sleep onset time (Mdiff = −12 min, p = 0.03), and sleep efficiency (Mdiff = 1.1%, p = 0.004)) and wrist activity monitor estimates (i.e., sleep onset time (Mdiff = −18 min, p = 0.01)). Insomnia severity scores decreased significantly (d = 0.47 [95% CI 0.08, 0.84], p = 0.001), while sleepiness scores increased but not meaningfully (d = 0.23 [95% CI −0.61, 0.14], p = 0.025). However, there was no significant change in mood (i.e., depression and anxiety) or cognitive performance scores (i.e., mean reaction time or lapses). Sleep interventions for esports athletes require further investigation. Future research should examine whether a stepped-care model, whereby increasing therapeutic input is provided as needed, can optimize sleep, mood, and cognitive performance outcomes.

Combination of ion exchange system and biological reactors for simultaneous removal of ammonia and organics.

A novel process for a simultaneous removal of ammonia and organics was developed on the basis of ion exchange and biological reactions. From batch experiments, it was found out that NH(4)(+) could be removed effectively by combining cation exchange and biological nitrification showing 0.98 mg N/m(2) ∙ s of a maximum flux. On the other hand, the removal of NO(3)(-) was 3.5 times faster than NH(4)(+) and the maximum flux was calculated to be 3.4 mg N/m(2) ∙ s. The systems for NH(4)(+) and NO(3)(-) removal were combined for establishing the IEBR process. When the process was operated in a continuous mode, approximately 95.8% of NH(4)(+) was removed showing an average flux of 0.22 mg N/m(2) · s. The removal efficiency of total nitrogen was calculated as 94.5% whereas that of organics was 99.5%. It was concluded that the IEBR process would be effectively used for a simultaneous removal of NH(4)(+) and organics.

Association between Diet Quality and Sarcopenia in Older Adults: Systematic Review of Prospective Cohort Studies.

(1) Background: Nutrition is a key determinant of sarcopenia in later life. (2) Methods: A systematic review of prospective cohort studies examining association of diet quality with muscle mass (MM), muscle strength (MS) or physical performance (PP) among older adults was conducted. A total of 22,885 results were obtained from a literature search in MEDLINE via PubMed and EMBASE up to November 2020. Inclusion criteria included diet quality assessment via dietary indices or statistical approaches, a sample of adults aged 45 years and over at baseline in a longitudinal study design. (3) Results: Of the 22,885 cohort studies, 14 studies were eligible. Meaningful results were obtained for the Mediterranean diet and Nordic diet regarding the decrease of sarcopenia risk, however results from non-European countries were inconsistent. In addition, due to the insufficient number of studies on Japanese Food Guide Spinning Top (JFG-ST), dietary variety score (DVS), and dietary quality index-international (DQI-I), effectiveness was difficult to prove. Studies using factor analysis to examine dietary patterns suggested that the risk of sarcopenia is increased with a high in saturated fat diet such as westernized pattern etc. (4) Conclusion: In this systematic review it was found that various diet qualities are meaningful to a decreased risk of sarcopenia.

Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment.

BACKGROUND: Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/ß-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT. METHODS: We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment. RESULTS: After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (-11.3%±1.6% relative to the baseline at 48 weeks, P<0.05). CONCLUSION: Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.

Improvement of mechanical properties of orodispersible hyaluronic acid film by carboxymethyl cellulose addition.

Orodispersible films (ODF) were prepared with mixtures of hyaluronic acid (HA) and carboxymethyl cellulose (CMC), and the effect of CMC addition on the disintegration and mechanical properties of the composite films were examined. Low molecular weight HA (10 kDa) appeared more acceptable for ODF than high molecular weight HA (800 kDa) because of its rapid disintegration in the oral cavity. The composite films appeared similar to pullulan film with excellent transparency and surface smoothness. The disintegration time as well as mechanical properties of the films such as tensile strength and elongation at break were increased by the addition of CMC. Overall, the CMC addition, up to 35%, improved the mechanical properties of low molecular weight HA film within a proper range of disintegration time for ODF.

Evaluation of New Octacalcium Phosphate-Coated Xenograft in Rats Calvarial Defect Model on Bone Regeneration.

Bone graft material is essential for satisfactory and sufficient bone growth which leads to a successful implant procedure. It is classified into autogenous bone, allobone, xenobone and alloplastic materials. Among them, it has been reported that heterogeneous bone graft material has a porous microstructure that increases blood vessels and bone formation, and shows faster bone formation than other types of bone graft materials. We observed new bone tissue formation and bone remodeling using Ti-oss® (Chiyewon Co., Ltd., Guri, Korea), a heterologous bone graft material. Using a Sprague-Dawley rat calvarial defect model to evaluate the bone healing effect of biomaterials, the efficacy of the newly developed xenograft Ti-oss® and Bio-Oss® (Geistilch Pharma AG, Wolhusen, Switzerland). The experimental animals were sacrificed at 8 and 12 weeks after surgery for each group and the experimental site was extracted. The average new bone area for the Ti-oss® experimental group at 8 weeks was 17.6%. The remaining graft material was 22.7% for the experimental group. The average new bone area for the Ti-oss® group was 24.3% at 12 weeks. The remaining graft material was 22.8% for the experimental group. It can be evaluated that the new bone-forming ability of Ti-oss® with octacalcium phosphate (OCP) has the bone-forming ability corresponding to the conventional products.

Cardiovascular Health Metrics in the Development and Regression of Nonalcoholic Fatty Liver Disease: A Cohort Study.

Cardiovascular Health (CVH) metrics scores are associated with cardiovascular disease but whether CVH scores are associated with nonalcoholic fatty liver disease (NAFLD) is uncertain. Our aim was to investigate associations between CVH scores and development or regression of NAFLD. A cohort study was performed in Korean adults who underwent a comprehensive health examination. The CVH metrics were defined according to the American Heart Association Life's Simple 7 metrics, ranging from 0 (all metrics considered unhealthy) to 7 (all metrics considered healthy). Fatty liver was diagnosed by ultrasound, and liver fibrosis assessed using NAFLD fibrosis score (NFS). Among 93,500 participants without NAFLD or fibrosis at baseline, 15,899 developed NAFLD, and 998 developed NAFLD plus intermediate/high NFS. Healthy CVH metrics were inversely associated with NAFLD and also NAFLD with fibrosis. In time-dependent models after updating the CVH score and confounders as time-varying covariate, the multivariable-adjusted hazard ratio (95% confidence intervals) for incident NAFLD plus intermediate/high NFS participants with CVH metrics score 2, 3, 4, 5, or 6-7 to those with score 0-1 were 0.86 (0.59-1.25), 0.51 (0.36-0.73), 0.44 (0.31-0.62), 0.20 (0.14-0.29) and 0.09 (0.05-0.14), respectively. Regression of NAFLD occurred in 9742/37,517 participants who had NAFLD at baseline with positive association with CVH metrics. Higher CVH scores were significantly associated with both (a) decreased incidence of NAFLD, and (b) regression of existing NAFLD. Promoting adherence to ideal CVH metrics can be expected to reduce the burden of NAFLD as well as cardiovascular disease.

Excessive nitric oxide attenuates leptin-mediated signal transducer and activator of transcription 3 activation.

The mechanisms of leptin resistance observed in most cases of human obesity are poorly understood. Therefore, we evaluated the effects of nitric oxide (NO) on the leptin-induced activation of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathways and on the leptin receptor (LEPR) expression using SH-SY5Y cells. Here, we show that the NO donor spermine/NONOate inhibited leptin-induced activation of STAT3 in vitro. The inhibition of leptin-mediated STAT3 phosphorylation caused by excessive NO was partially prevented by a sulfhydryl reducing agent, ascorbic acid. Cellular experiments show that reduced expression of long form leptin receptor (LEPR-b) and STAT3 protein instability induced by NO may be mechanisms of the NO-mediated inhibition of leptin-STAT3 signaling. We also present data showing that the hypothalamic NO content of high-fat (HF)-diet-induced obese mice was higher than that of control mice; this is likely caused by decreased caveolin-1 expression and increased nNOS expression induced by HF diet over 19 weeks. Concurrently with the overproduction of NO, the decrease of hypothalamic LEPR-b in obese mice also supports these in vitro data. Combined results suggest that excess of NO can induce the attenuation of leptin-mediated STAT3 activation through reduced expression of LEPR-b mRNA and instability of STAT3 protein at least in part. Furthermore, our in vivo data indicate that long-term HF diet induces hypothalamic overproduction of NO, which may be related with leptin insensitivity. However, further study is required to warrant direct in vivo evidence of a causal relationship between endogenous excess of hypothalamic NO and central leptin resistance.

Defect-induced ripening of zeolitic-imidazolate framework ZIF-8 and its implication to vapor-phase membrane synthesis.

We report for the first time that ZIF-8 crystals undergo an Ostwald-ripening-like process without degradation in the presence of a ligand vapor. The ripening process is dependent on the defect density of the crystals: the more defective the more amenable to the ripening. The process was adapted to synthesize ultra-thin ZIF-8 membranes by vapor-phase secondary growth.

Enhanced susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in high-fat diet-induced obesity.

Currently, obesity is considered a systemic inflammation; however, the effects of obesity on the vulnerability of dopaminergic neurons to oxidative stress are not fully defined. We evaluated the effects of high-fat diet-induced obesity (HF DIO) on neurotoxicity in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Eight weeks after a HF or matched normal diet, a severe decrease in the levels of striatal dopamine and of nigral microtubule-associated protein 2, manganese superoxide dismutase, and tyrosine hydroxylase was observed in obese mice treated with subtoxic doses of MPTP (20 mg/kg) compared with the matched lean group. In addition, the levels of nitrate/nitrite and thiobarbituric acid-malondialdehyde adducts in the substantia nigra of obese mice were reciprocally elevated or suppressed by MPTP. Interestingly, striatal nNOS phosphorylation and dopamine turnover were elevated in obese mice after MPTP treatment, but were not observed in lean mice. The nitrotyrosine immunoreactivity for evaluation of nigral nitrogenous stress in obese mice with MPTP was higher than that in matched lean mice. At higher doses of MPTP (60 mg/kg), the mortality was higher in obese mice than in lean mice. These results suggest that DIO may increase the vulnerability of dopaminergic neurons to MPTP via increased levels of reactive oxygen and nitrogen species, and the role of nNOS phosphorylation in the MPTP toxicities and dopamine homeostasis should be further evaluated.