Search

Purpose: Infants in the neonatal intensive care unit (NICU) often show cardiorespiratory deterioration during gavage feeding. We aimed to determine whether slow infusion intermittent feeding (SIIF) can reduce respiratory deterioration during gavage feeding in preterm infants in the NICU.Methods: Data on preterm infants whose gavage feeding method was changed to SIIF (1-­­hour infusion with an infusion pump and 2-­hour rest within a 3­-hour interval) from bolus gravity feeding (2-­ or 3-­hour interval) due to feeding­-associated cardiorespiratory deterioration were retrospectively reviewed. A significant cardiorespiratory event was defined as a saturation level below 80% or heart rate below 80 bpm. We compared the frequency of cardiorespiratory events and the level of respiratory support 24 hours before and after the application of SIIF.Results: A total of 34 infants were enrolled and analyzed. The total frequency of desaturation or bradycardia significantly decreased after SIIF application (8.94 vs. 5.03, P=0.001). The frequency of feeding­related bradycardia and desaturation also significantly decreased (4.15 vs. 1.68, P=0.008). Out of 34 patients, 11 (32.4%) had a decreased level of ventilator support within 1 day after SIIF. The respiratory severity scores of the 10 patients who received invasive ventilator support decreased significantly after SIIF (5.24 vs. 4.59, P=0.032).Conclusion: SIIF significantly decreased gavage feeding­associated cardiorespiratory events and reduced respiratory support in approximately one­third of subjects. Therefore, SIIF may be a therapeutic option for gavage feed­associated respiratory deterioration in preterm infants in the NICU.

This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1–3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-β-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary gland. Although characterized as an indolent tumor, ACC often leads to incurable metastatic disease. Patients with ACC respond poorly to currently available therapeutic drugs and factors contributing to the limited response remain unknown. Determining the role of molecular alterations frequently occurring in ACC may clarify ACC tumorigenesis and advance the development of effective treatment strategies. Applying Splice Expression Variant Analysis and outlier statistics on RNA sequencing of primary ACC tumors and matched normal salivary gland tissues, we identified multiple alternative splicing events (ASE) of genes specific to ACC. In ACC cells and patient-derived xenografts, FGFR1 was a uniquely expressed ASE. Detailed PCR analysis identified three novel, truncated, intracellular domain-lacking FGFR1 variants (FGFR1v). Cloning and expression analysis suggest that the three FGFR1v are cell surface proteins, that expression of FGFR1v augmented pAKT activity, and that cells became more resistant to pharmacologic FGFR1 inhibitor. FGFR1v-induced AKT activation was associated with AXL function, and inhibition of AXL activity in FGFR1v knockdown cells led to enhanced cytotoxicity in ACC. Moreover, cell killing effect was increased by dual inhibition of AXL and FGFR1 in ACC cells. This study demonstrates that these previously undescribed FGFR1v cooperate with AXL and desensitize cells to FGFR1 inhibitor, which supports further investigation into combined FGFR1 and AXL inhibition as an effective ACC therapy.This study identifies several FGFR1 variants that function through the AXL/AKT signaling pathway independent of FGF/FGFR1, desensitizing cells to FGFR1 inhibitor suggestive of a potential resistance mechanism in ACC.Significance:This study identifies several FGFR1 variants that function through the AXL/AKT signaling pathway independent of FGF/FGFR1, desensitizing cells to FGFR1 inhibitor, suggestive of a potential resistance mechanism in ACC.

Supplemental Data S1 provides description on the ACC-01-XP xenograft development using ACC-01 cell line and shows list of PCR primers and other reagents used in the study. Supplemental Data S2 shows list of alternative splicing events identified in ACC compared to normal salivary gland tissue. Supplemental Data S3 shows nucleotides and corresponding amino acid composition of the three novel FGFR1 splice variants. Figure S1 shows ASE genes in PI3K-AKT signaling pathway enrichment using the Enrichr web tool. Figure S2 shows characterization of FGFR1v and impact on cell growth following siRNA-mediated knockdown. Figure S3 shows FGFR1v stability analysis and its effect on signaling and resistance to FGFR1 inhibitor. Figure S4 shows FGFR1v-mediated AKT signaling is independent on EGFR but supports the involvement of AXL. Figure S5 shows supportive expression and activities of FGFR1v in HACC-2A cells.

We aimed to derive comprehensive MRI parameters that reflect intramuscular fat infiltration severity for designated lower extremity levels, based on semiquantitative analyses in Charcot-Marie-Tooth disease type 1A (CMT1A) patients. We reviewed lower extremity MRIs of 116 CMT1A patients. Intramuscular fat infiltration grading using the Mercuri scale was performed for the non-dominant lower extremity at three levels (proximal, mid, and distal) for the thigh and at two levels (proximal and distal) for the lower leg. Based on MRI results, the following parameters were calculated for each level and for entire muscles: fat infiltration proportion (FIP), significant fat infiltration proportion (SigFIP), and severe fat infiltration proportion (SevFIP). The relationships between the MRI parameters and clinical data were evaluated using Spearman’s correlation analysis. FIP, SigFIP, and SevFIP measured for entire muscles significantly correlated with Charcot-Marie-Tooth Neuropathy Score (p p p = 0.0003, 0.0010, and 0.0011), and disease duration (p

The objectives of this study were to assess changes in apparent diffusion coefficient (ADC) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters after radiation therapy (RT) for bone metastases from hepatocellular carcinoma (HCC) and to evaluate their prognostic value. This prospective study was approved by the Institutional Review Board. Fourteen patients with HCC underwent RT (30 Gy in 10 fractions once daily) for bone metastases. The ADC and DCE-MRI parameters and the volume of the target lesions were measured before (baseline) and one month after RT (post-RT). The Wilcoxon signed-rank test was used to compare the parameters between the baseline and post-RT MRI. The parameters were compared between patients with or without disease progression in RT fields using the Mann–Whitney test. Intraclass correlation coefficients were used to evaluate the interobserver agreement. The medians of the ADC, rate constant [kep], and volume fraction of the extravascular extracellular matrix [ve] in the baseline and post-RT MRI were 0.67 (range 0.61–0.72) and 0.75 (range 0.63–1.43) (× 10–3 mm2/s) (P = 0.027), 836.33 (range 301.41–1082.32) and 335.80 (range 21.86–741.87) (× 10–3/min) (P = 0.002), and 161.54 (range 128.38–410.13) and 273.99 (range 181.39–1216.95) (× 10–3) (P = 0.027), respectively. The medians of the percent change in the ADC of post-RT MRI in patients with progressive disease and patients without progressive disease were − 1.35 (range − 6.16 to 6.79) and + 46.71 (range 7.71–112.81) (%) (P = 0.011), respectively. The interobserver agreements for all MRI parameters were excellent (intraclass correlation coefficients > 0.8). In conclusion, the ADC, kep, and ve of bone metastases changed significantly after RT. The percentage change in the ADC was closely related to local tumor progression.

We propose a stabilization method for a Q-switched composite YAG/Yb:YAG/Cr:YAG laser configured for use as a laser igniter. The method is based on reducing the fluctuations in the magnitude of the initial seed signal caused by interference of the initial resonator modes. We have shown that a stable laser output could be achieved using a Fabry-Perot etalon, which can reduce the number of modes, to reduce the initial noise fluctuation in a resonator.

A collective synthetic route for tricyclic guaiane sesquiterpenes and total syntheses of (+)-dysodensiol F, (+)-10β,14-dihydroxy-allo-aromadendrane, and (-)-dendroside C aglycon starting from a versatile hydroazulene intermediate were accomplished. The key features of these syntheses involve late-stage carbene-mediated diastereoselective cyclopropanation, construction of an unusual cis-fused-hydroazulene skeleton via intramolecular Dieckmann condensation, and highly stereoselective tandem conjugate addition/intramolecular allylic alkylation to afford a 5/7/3 tricyclic skeleton of guaiane natural products. The synthesis of (-)-dendroside C aglycon and the first total synthesis of (+)-dysodensiol F and (+)-10β,14-dihydroxy-allo-aromadendrane are described in detail. Activation of the Nrf2/ARE signaling pathway by (-)-dendroside C aglycon is also disclosed via our synthesis.

In this study, we explored whether the use of Streptococcus thermophilus LM1012 (TL-LM1012) as a safe probiotic exerts hepatoprotective effects by suppressing oxidative stress and inflammation in vitro and alleviating aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) production in vivo. In a series of safety tests, TL-LM1012 was found to have a negative response to hemolysis and biogenic amines, as well as susceptibility to antibiotics. TL-LM1012 protected cell viability and suppressed cytotoxicity by inhibiting oxidative stress and induced heme oxygenase-1 and superoxide dismutase activity in a dose-dependent manner in diesel exhaust particulate matter (DEPM)-treated HepG2 cells. Moreover, proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, were suppressed in DEPM-treated splenocytes. In DEPM-treated mice, oral administration of TL-LM1012 regulated AST, ALT, and LDH production in the serum after 14 days of treatment. These findings indicate that TL-LM1012, a safe probiotic, provides a potent preventive or therapeutic effect against liver disease caused by air pollution.

A telling feature of modern musical education is the well-established schism between theory and practice. This dichotomy is most directly observed in the two currently prevailing institutions for m...

Purpose Spinal muscular atrophy (SMA) is a genetic progressive neuromuscular disorder, and nusinersen has shown to improve its symptoms. Scoliosis is a frequent symptom in patients with SMA and complicates the intrathecal injection of nusinersen. The aim of this study was to investigate the safety and effectiveness of fluoroscopy-guided intrathecal injections in patients with SMA with severe scoliosis. Methods We retrospectively reviewed the medical records of 11 patients with SMA treated with nusinersen intrathecal injections at the Samsung Medical Center from 2018 to 2020. We assessed the type of SMA, genetic results, spine computed tomography or fluoroscopy findings, and adverse effects associated with the injection. Results Of 11 patients with SMA, six were diagnosed with severe scoliosis, four of whom underwent an operation for scoliosis. The six patients with severe scoliosis started receiving the nusinersen injection at a median age of 15.7 years. A total of 25 injections were completely performed with the interlaminar approach (ILA) at the lumbar level under C-arm fluoroscopy guidance. No adverse effects other than mild headache occurred. In one patient who underwent the complete fusion operation for scoliosis, laminectomy was performed for the nusinersen injection, and 3 doses were administered intrathecally via the interlaminar route at the lumbar level. Conclusion Fluoroscopy-guided ILA is a safe method for the intrathecal injection of nusinersen in patients with SMA with severe scoliosis. When defining the route, laminectomy might be necessary to open the window for the ILA route at the lumbar level.

Although the obesity paradox is a topic of immense interest for oncologists and epidemiologists, the mechanism underlying this unexpected benefit of obesity is poorly understood. We explored the prognostic value of obesity and its association with skeletal muscle mass.This retrospective study evaluated the data of patients who underwent surgical excision for lung adenocarcinoma between January 2011 and December 2015. Body mass index was categorized according to the criteria of the Asia-Pacific classification. Cross-sectional areas of the skeletal muscle, subcutaneous fat, and visceral fat were measured. Skeletal muscle mass status was defined based on the cut-offs of skeletal muscle index (cmA total of 636 patients with a median age of 61 years (interquartile range, 54.0-68.5 years; 321 men and 315 women) were included. Obese patients (body mass index ≥ 25 kg/mObesity was associated with favourable overall survival, independent of skeletal muscle mass, after surgical excision of lung adenocarcinoma.

Fibrosis has various biological processes and affects almost every organ, especially in patients with inflammatory bowel disease, including Crohn’s disease, who experience discomfort caused by intestinal fibrosis, which is a problem that needs to be resolved. TGF-β signaling is known to act as a key regulator of intestinal fibrosis, and its modulation could be an excellent candidate for fibrosis therapy. Xanthohumol (XN) has various effects, including anti-inflammation and anti-cancer; however, the detailed mechanism of TGF-β signaling has not yet been studied. The purpose of this study was to investigate the mechanism underlying the anti-fibrotic effect of XN on TGF-β1-induced intestinal fibrosis using primary human intestinal fibroblasts (HIFs). In this study, to check the anti-fibrotic effects of XN on intestinal fibrosis, we assessed the expression of fibrosis-related genes in TGF-β1-stimulated HIFs by qPCR, immunoblotting, and immunofluorescence staining. As a result, XN showed the ability to reduce the expression of fibrosis-associated genes increased by TGF-β1 treatment in HIFs and restored the cell shape altered by TGF-β1. In particular, XN repressed both NF-κB- and Smad-binding regions in the α-SMA promoter, which is important in fibrosis. In addition, XN inhibited NF-κB signaling, including phosphorylated-IkBα and cyclooxygenase-2 expression, and TNF-α-stimulated transcriptional activity of NF-κB. XN attenuated TGF-β1-induced phosphorylation of Smad2 and Smad3, and the transcriptional activity of CAGA. Particularly, XN interfered with the binding of TGF-Receptor I (TβRI) and Smad3 by binding to the kinase domain of the L45 loop of TβRI, thereby confirming that the fibrosis mechanism did not proceed further. In conclusion, XN has an inhibitory effect on TGF-β1-induced intestinal fibrosis in HIFs, significantly affecting TGF-β/Smad signaling.

The discovery of small molecules that regulate specific neuronal phenotypes is important for the development of new therapeutic candidates for neurological diseases. Estrogen-related receptor γ (ERRγ), an orphan nuclear receptor widely expressed in the central nervous system (CNS), is closely related to the regulation of neuronal metabolism and differentiation. We previously reported that upregulation of ERRγ could enhance dopaminergic neuronal phenotypes in the neuroblastoma cell line, SH-SY5Y. In this study, we designed and synthesized a series of new ERRγ agonists using the X-ray crystal structure of the GSK4716-bound ERRγ complex and known synthetic ligands. Our new ERRγ agonists exhibited increased transcriptional activities of ERRγ. In addition, our molecular docking results supported the experimental findings for ERRγ agonistic activity of the potent analogue, 5d. Importantly, 5d not only enhanced the expression of dopaminergic neuronal-specific molecules, TH and DAT but also activated the relevant signaling events, such as the CREB-mediated signaling pathway. The results of the present study may provide useful clues for the development of novel ERRγ agonists for neurological diseases related to the dopaminergic nervous system.

The objectives of this study were to assess the fat fraction (FF) and cross-sectional area (CSA) of the sciatic nerve in Charcot-Marie-Tooth disease type 1A (CMT1A) patients using Dixon-based proton density fat quantification MRI and to elucidate its potential association with clinical parameters. Thigh MRIs of 18 CMT1A patients and 18 age- and sex-matched volunteers enrolled for a previous study were reviewed. Analyses for FF and CSA of the sciatic nerve were performed at three levels (proximal to distal). CSA and FF were compared between the two groups and among the different levels within each group. The relationship between the MRI parameters and clinical data were assessed in the CMT1A patients. The CMT1A patients showed significantly higher FF at level 3 (p = 0.0217) and significantly larger CSA at all three levels compared with the control participants (p < 0.0001). Comparisons among levels showed significantly higher FF for levels 2 and 3 than for level 1 and significantly larger CSA for level 2 compared with level 1 in CMT1A patients. CSA at level 3 correlated positively with the CMT Neuropathy Score version 2 (CMTNSv2). In conclusion, the sciatic nerve FF of CMT1A patients was significantly higher on level 3 compared with both the controls and the measurements taken on more proximal levels, suggesting the possibility of increased intraepineurial fat within the sciatic nerves of CMT1A patients, with a possible distal tendency. Sciatic nerve CSA at level 3 correlated significantly and positively with CMTNSv2, suggesting its potential value as an imaging marker for clinical severity.

Ionic liquids (ILs) have attracted significant interest because of their desirable properties. These characteristics have improved their application to overcome the shortcomings of conventional separation techniques for phytochemicals. In this study, several ILs were investigated for their capacity to extract isoimperatorin, a bioactive furanocoumarin, from the roots of Ostericum koreanum. Herein, 1-Butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) was selected as a promising IL for separating isoimperatorin. A central composite design was applied to optimize the extraction conditions. Under the optimal conditions, the yield of isoimperatorin reached 97.17 ± 1.84%. Additionally, the recovery of isoimperatorin from the [Bmim][BF4] solution was successfully achieved (87.73 ± 2.37%) by crystallization using water as an antisolvent. The purity of the isoimperatorin was greatly enhanced, from 0.26 ± 0.28% in the raw material to 26.94 ± 1.26% in the product, in a one-step crystallization process. Namely, an enhancement of approximately 103-folds was reached. The developed approach overcomes the shortcomings of conventional separation methods applied for gaining isoimperatorin by significantly reducing the laboriousness of the process and the consumption of volatile organic solvents. Moreover, the simplicity and effectiveness of the method are assumed to be valuable for producing isoimperatorin-enriched products and for promoting its purification. This work also confirms the efficiency of ILs as a promising material for the separation of phytochemicals.

Although radiation therapy (RT) plays an important role in the palliation of localized bone metastases, there is no consensus on a reliable method for evaluating treatment response. Therefore, we retrospectively evaluated the potential of magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) maps and conventional images in whole-tumor volumetric analysis of texture features for assessing treatment response after RT. For this purpose, 28 patients who received RT for osteolytic bone metastasis and underwent both pre- and post-RT MRI were enrolled. Volumetric ADC histograms and conventional parameters were compared. Cox regression analyses were used to determine whether the change ratio in these parameters was associated with local disease progression-free survival (LDPFS). The ADCmaximum, ADCmean, ADCmedian, ADCSD, maximum diameter, and volume of the target lesions after RT significantly increased. Change ratios of ADCmean < 1.41, tumor diameter ≥ 1.17, and tumor volume ≥ 1.55 were significant predictors of poor LDPFS. Whole-tumor volumetric ADC analysis might be utilized for monitoring patient response to RT and potentially useful in predicting clinical outcomes.

With the transition of EUV lithography to high volume manufacturing, EUV mask metrology has become a critical requirement. At PSI, we are developing RESCAN, a lensless actinic microscope dedicated to EUV mask inspection. RESCAN is based on coherent diffraction imaging (CDI), a method that reconstructs the complex image of the sample through its diffraction spectrum measured with a CCD detector. While this approach can overcome the cons and limitations of traditional optical imaging systems, in CDI, the quality of the recorded diffraction data is crucial for the reliable reconstruction of a high-resolution image. Ultimately, the signal-to-noise ratio of the recorded diffraction data depends on several parameters, such as the reflectance of the sample, the quantum efficiency of the detector, its full well capacity, and the intensity of the illumination. This paper investigates the optimal photon flux for RESCAN and analyzes the relation between the image quality and the EUV illumination intensity for a CDI-based imaging tool dedicated to EUV mask inspection and review.

The urban ecosystem provides many services that help humans lead physically and mentally healthy lives. The quality of such urban ecosystem services is closely related to various urban forms, such as land cover, land use, buildings, infrastructure, population, and type and scale of green space. This study aims to promote the overall improvement and balance of an urban ecosystem’s regulating services. Initially, ecosystem regulating services are assessed according to the type of the urban space, and their contributions are analyzed based on linear regression slope and pairwise comparison of the ecosystem services. The contribution of ecosystem regulating services of Suwon City in South Korea was assessed through the following process: (1) selection of assessment indices and assessment methods for urban ecosystem regulating services, (2) urban space classification, (3) ecosystem regulating service assessment by type of urban space, and (4) pairwise comparison of ecosystem regulating services by type and for the entire study area. The study areas are classified into six type areas: forests (type A), agricultural land (type B), low-rise residential areas (type C), mid-rise mixed (residential and commercial) areas (type D), high-rise residential areas (type E), and industrial and barren land (type F). By studying representative regulating services, such as vegetation vitality, flood reduction capacity, carbon storage capacity, and heat reduction capacity, this study confirmed that type A provided the best service, while type C provided the worst. In addition, the relative contribution analysis between the regulating services based on pairwise comparison showed that the standard deviation between the contributions was 0.04 when diagnosing the entire study area, but apparently no types except type A were balanced. The reason such regulating services are imbalanced is that their vegetation vitality was calculated to be the lowest compared with the assessment indices of type A. Additionally, this imbalance was found to be most severe in the mid-rise mixed (residential and commercial) districts. Through this study, the spatial types in which the ecosystem regulating services in Suwon City are imbalanced could be determined. It was also revealed that regulating services should be prioritized for improvement in order to achieve greater balance in urban ecosystem. Such pairwise comparison results can be effectively utilized in determining the area and supply needed when formulating urban greening plans and forest restoration plans.

EUV photomasks define the lithographic layers of chips, which are binary structures of relatively low versatility in contrast to specimen in biology or materials science. This knowledge can be used in EUV photomask imaging and inspection methods to improve the speed or sensitivity. We present here a total variation-based phase retrieval algorithm similar to previous methods by Chang et al. and Enfedaque et al. for EUV mask imaging and metrology. Total variation (TV) regularization exploits the binary structure of the reticles, enforcing a sparse sample gradient. We compare the TV regularized algorithm, PtychoADMM, to a standard phase retrieval approach, the difference map (DM). For simulated data containing Poisson noise, we do not observe a benefit from using the TV based PtychoADMM algorithm. The reconstructed image quality is similar, while PtychoADMM being a computationally more demanding method. In future, we will investigate if TV can recover information where the standard DM approach fails, e.g. for relaxed measurement requirements like a lower signal to noise ratio or less probe overlap in the ptychography scan.

The present study investigated the immunomodulatory activity and associated mechanisms of heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) in a cyclophosphamide (CTX)-induced mouse model of immunosuppression. HT-LM1004 induced phagocytic activity and nitric oxide production in RAW264.7 macrophages and stimulated the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, and IL-12p70. In mice with CTX-induced immunosuppression, oral HT-LM1004 administration restored thymus and spleen indices, including spleen weight. Consistent with the in vitro results, HT-LM1004 increased TNF-α, IFN-γ, IL-2, and IL-12p70 levels in mice after 14 days of treatment and enhanced the natural killer (NK) cell activity of splenocytes from mice with CTX-induced immunosuppression against YAC-1 lymphoma cells. The method of HT-LM1004 generation influenced this activity: L. plantarum LM1004 grown in a membrane bioreactor, which reduced the size of the cells to

We propose a passively coherent combined polarization beam system composed of a polarization Michelson interferometer and a two-pass amplifier. We investigate the output characteristics, such as the output power, spectrum, and intensity autocorrelation signal of the two-pulse combined beam, and compare the results with one of the two divided pulses utilized for the beam combination. We found that the intensity autocorrelation signal width difference between the two compared beams was less than 1%.

Background This study aimed to evaluate the potential value of 3D multiple gradient echo Dixon‐based magnetic resonance imaging (MRI) sequence as a tool for thigh intramuscular fat quantification in Charcot–Marie–Tooth disease (CMT) patients. Methods A prospective comparison study comprising 18 CMT patients and 18 age/sex‐matched volunteers was performed. MRI including 3D multiple gradient echo Dixon‐based imaging was performed for each subject. Region of interest analyses were performed at the upper and lower third of both thighs. The two‐sample t‐test or Wilcoxon rank sum test was used for intergroup comparison of the mean muscle fat fraction. Intraclass correlation coefficients were used to evaluate the interobserver agreement and test–retest reproducibility. Semiquantitive analysis using the Goutallier classification (Grades 0–4) was performed on T1‐weighted images in upper thigh muscles. For Goutallier Grade 0 muscles, comparison of the mean intramuscular fat fraction between volunteers and CMT patients was performed. Results The interobserver agreements were excellent for all measurements (intraclass correlation coefficients > 0.8). Mean muscle fat fractions were significantly higher in all the measured muscles of CMT patients (P

Long-term evaluation from 2000 to 2020 of a temperate reservoir indicated that water quality and trophic status were not critically controlled by the inter-annual dynamics of monsoon precipitation. The fluctuation of annual concentrations of TP, TSS, and EC did not always correlate with the variation of precipitation. BOD and COD demonstrated monotonically increasing trends with Sen’s slope of 0.02 and 0.01, respectively, while Chl-a manifested a decreasing trend (slope = −0.23). The increases of different magnitudes in the levels of TP, TSS, and Chl-a in the monsoon and the early post-monsoon periods were observed in the drought, flood, and normal years. The drought years showed distinct seasonal variations in many parameters, while those in the flood and the normal years were very similar. Pearson correlation and empirical regression analyses resulted in weaker correlation between water quality and hydrological parameters than other reservoirs, which, along with low impact of precipitation, was attributed to the low drainage ratio (28.8) of the study area. BOD/COD ratios were higher than 0.5 in the reservoir, indicating the presence of a significant fraction of biodegradable organic matter. The ratio increased in the longitudinal flow direction (&gt, 50% in the drought years), implying the possibility of autochthonous sources of organic matter. TSID evaluation resulted in variation of limiting factors not related to the fluctuation of annual precipitation. The loadings of the significant principal components were very similar among the different precipitation groups, supporting the other findings that annual precipitation governed by monsoon intensity would not solely control the water quality dynamics of the study area.

The variations in water quality parameters and trophic status of a multipurpose reservoir in response to changing intensity of monsoon rain was investigated by applying a trophic state index deviation (TSID) analysis and an empirical regression model to the data collected in two periods from 2014 to 2017. The reservoir in general maintained mesotrophic conditions, and Carlson’s trophic state index (TSIc) was affected most by TSITP. Nutrient concentrations, particularly phosphorus, did not show strong correlations with precipitation, particularly in the period with weak monsoon, and a significant increase in total phosphorus (TP) was observed in Spring 2015, indicating the possibility of internal phosphorus loading under decreased depth and stability of water body due to a lack of precipitation. TSIChl was higher than TSISD in most data in period 1 when a negligible increase in precipitation was observed in the monsoon season while a significant fraction in period 2 showed the opposite trend. Phytoplankton growth was not limited by nutrient limitation although nutrient ratios (N/P) of most samples were significantly higher than 20, indicating phosphorus-limited condition. TSID and regression analysis indicated that phytoplankton growth was limited by zooplankton grazing in the Spring, and that cell concentrations and community structure in the monsoon and post-monsoon season were controlled by the changing intensity of the monsoon, as evidenced by the positive and negative relationships between community size and cyanobacterial population with the amount of precipitation in the Summer, respectively. The possibility of contribution from internal loading and an increase in cyanobacterial population associated with weak monsoon, in addition to potential for nutrient enrichment in the post-monsoon season, implies a need for the application of more stringent water quality management in the reservoir that can handle all potential scenarios of eutrophication.

The first total syntheses of isocorniculatolide B, corniculatolide B, and corniculatolide C, consisting of isomeric corniculatolide skeletons, have been accomplished in a divergent manner. The key features of the synthesis involve the construction of diaryl ether linkages by nucleophilic aromatic substitution, installation of a C14-substituted alkyl side chain via a sequence of Baeyer-Villiger reaction and Claisen rearrangement, and efficient construction of corniculatolide and isocorniculatolide frameworks, including 17-membered (exterior) macrolactone skeletons from a versatile diaryl ether intermediate by Mitsunobu macrolactonization. Moreover, we prepared the structural congeners of isomeric corniculatolides via diverted total synthesis approach including desmethyl analogues and related dimeric macrolides. The anti-inflammatory activities of the synthesized natural products, analogues and synthetic intermediates were also investigated. In particular, corniculatolide B significantly inhibited the protein expression of COX-2 and the mRNA expressions of TNF-α, IL-1β and IL-6 by inhibiting of NF-κB signaling in intestinal epithelial cells induced by lipopolysaccharide treatment. It also significantly inhibited the promoter activity and the phosphorylation of subunits p50 and p65 of NF-κB to the same extent as Bay 11-7082, a potent IκB kinase inhibitor. These results suggest that corniculatolide B might have therapeutic potential in inflammatory bowel disease via NF-κB signaling pathway.

Silicalite-1 core/Al-ZSM-5 shell zeolite crystals were prepared in various sizes for use as catalysts in methane dehydroaromatization (MDA), and the growth kinetics and corresponding physicochemical properties of this core–shell zeolite were investigated. Al-ZSM-5 was grown on silicalite-1 seeds at various Si/Al ratios. Core–shell catalysts of all size variations exhibited similar deactivation trends in the MDA reaction, with minor changes in aromatic yields despite clear differences in reaction channel lengths and acid-site properties. This outcome was shown to originate from the unique growth kinetics of the Al-ZSM-5 layer on silicalite-1 seeds, in which the Al species in the sol used in the synthesis were consumed quickly during the early aggregative growth period. This led to an interesting spatial distribution of Al in the Al-ZSM-5 layer, in that the inner layer was relatively Al-rich. This distribution is advantageous because it can inhibit coke deactivation, which often occurs at the catalyst surface during MDA. However, a substantial quantity of Si–OH nests, which inhibit the effective loading of Mo species at the acid sites of the crystals, were detected in the microstructural analysis of large crystals. Therefore, this study shows that silicalite-1 core/Al-ZSM-5 shell zeolites can be prepared for use as coke-resistant catalysts for the MDA reaction. Further work is required, however, to design a synthesis method which reduces the number of Si–OH nests formed.