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A new natural indole, vibrindole B (1), together with known analogs, vibrindole A (2), trisindoline (3), norharmane (4), and 3-(hydroxyacetyl)indole (5), produced by the bacterium Pseudovibrio denitrificans P81, were isolated from a sponge, Aaptos species. The structures of indoles 1 to 5 were established by spectroscopic methods. The proposed biosynthetic pathway of 1 to 5 is also discussed, starting from tryptophan. Moreover, indoles 1 to 3 were found to exhibit cytotoxicity toward T24 tumor cells with IC50 values of 1.71 ± 0.11, 4.53 ± 0.14, and 2.26 ± 0.26 µM, respectively.

Composite photocatalysts comprising graphitic carbon nitride (g-C3N4) and graphene materials were synthesized and evaluated in the photocatalysis of bisphenol A (BPA) with a focus on elucidating the reaction mechanism. Embedding reduced graphene oxide (rGO) to g-C3N4 significantly accelerated the photocatalysis rate of BPA by three folds under visible light irradiation at neutral pH. We showed that rGO synthesized in intimate contact with g-C3N4 increased the surface areas and electrical conductivity of the g-C3N4 composites and promoted the electron-hole pair separation. The BPA photodegradation mechanism involved selective oxidants as superoxide (O2•−) and singlet oxygen (1O2) that were formed through one-electron reduction of O2 and the unique oxidation of O2•− by photogenerated hole (h+), respectively. The synthesized photocatalyst exhibited superior visible light photoreactivity to that of N-doped P25 TiO2, good photo-stability and reuse potential, and was operative in complex wastewater. rGO embedded g-C3N4 achieved good photomineralization of BPA at 80% in 4 h compared to 40% of bare g-C3N4. This study sheds light on the photocatalysis mechanism of BPA with a metal-free, promising rGO/g-C3N4 photocatalyst.

Deception has been reported to be influenced by task-relevant emotional information from an external stimulus. However, it remains unclear how task-irrelevant emotional information would influence deception. In the present study, facial expressions of different valence and emotion intensity were presented to participants, where they were asked to make either truthful or deceptive gender judgments according to the preceding cues. We observed the influence of facial expression intensity upon individuals' cognitive cost of deceiving (mean difference of individuals' truthful and deceptive response times). Larger cost was observed for high intensity faces compared to low intensity faces. These results provided insights on how automatic attraction of attention evoked by task-irrelevant emotional information in facial expressions influenced individuals' cognitive cost of deceiving.

Two novel 16-membered tetraene marcolides, bafilomycins N (1) and O (2), along with two known analogues, JBIR-100 (3) and bafilomycin K (4) were produced from isolate GIC10-1, a Streptomyces sp. strain that was originally cloned from bacterial communities associated with marine sponge Theonella sp. The structures of new bafilomycins 1 and 2 were established by using spectroscopic methods and comparing the spectroscopic data with those of known related metabolites. Compounds 1 and 2 were proven to be the first 14-methylbafilomycins to be isolated. Cytotoxicity of these compounds toward various cancer cell lines also is described.

We generalize the recently developed kinetic energy partition (KEP) method for systems with two competing interactions to solve the quantum eigenvalue problems of a particle interacting with a number of harmonic-oscillator potentials. First, the original formulation of the KEP method is extended to the case with many interaction potentials. Second, we apply the method to the two and three harmonic-oscillators problems, respectively. Finally, the general N harmonic-oscillators system is considered and solved. We show that the KEP method can yield the exact solutions very accurately and efficiently.

In this work, we developed a concise synthetic route for the synthesis of polysubstituted naphthalenes starting from commercially available isovanillin and its derivatives. Reaction with styryl bromide via O-styrylation, Claisen rearrangement, ene reaction, and O-alkylation occurred in high yields. The key structures were confirmed by single-crystal X-ray diffraction.

Prodigiosin (PG), a red tripyrrole pigment, belongs to a member of the prodiginine family and is normally secreted by various sources including Serratia marcescens and other Gram-negative bacteria. The studies of PG have received innovative devotion as a result of reported antimicrobial, larvicidal and anti-nematoid immunomodulation and antitumor properties, owing to its antibiotic and cytotoxic activities. This review provides a comprehensive summary of research undertaken toward the isolation and structural elucidation of the prodiginine family of natural products. Additionally, the current evidence-based understanding of the biological activities and medicinal potential of PG is employed to determine the efficacy, with some reports of information related to pharmacokinetics, pharmacodynamics and toxicology.

Background Obesity and its associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are a particular worldwide health problem at present. Momordica cochinchinensis fruit is consumed widely in Southeast Asia. However, whether it has functional effects on fat-induced metabolic dysfunction and gut microbiota remains unclear. This study was conducted to determine how Momordica cochinchinensis aril (MCA) affects obesity, nonalcoholic fatty liver, insulin resistance and gut microbiota in diet-induced obese mice.Methods Wild type male mice at age of 5 weeks received four different kinds of diets: a normal diet, high-fat diet (HFD), or HFD supplemented with 1% or 3% (wt:wt) lyophilized MCA for 10 weeks. Body weight, adipose tissue and liver weight, serum biochemical parameters, glucose tolerance and liver lipids were measured. Gut microbial composition was analyzed.Results MCA protected the mice against high-fat diet (HFD)-induced body weight gain, hyperlipidemia and hyperglycemia, compared with mice that were not treated. MCA inhibited the expansion of adipose tissue and adipocyte hypertrophy. In addition, the insulin sensitivity-associated index that evaluates insulin function was also significantly restored. MCA also regulated the secretion of adipokines in HFD-induced obese mice. Moreover, hepatic fat accumulation and liver inflammation were reduced, which suggested that fatty liver was prevented by MCA. Furthermore, MCA supplementation suppressed hepatic lipid accumulation by activation of AMPK and PPAR-alpha signaling pathway in the human fatty liver HuS-E/2 cell model. Supplementation with MCA resulted in microbiota populations changed significantly.Conclusion Our data indicate that dietary MCA is involved in the prevention of HFD-induced adiposity, insulin resistance and nonalcoholic fatty liver disease and altered the microbial contents of the gut and modulated microbial dysbiosis in the host.

Additional file 1. STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies

In the current study, an NMR spectroscopic pattern-based procedure for probing scalarane derivatives was performed and four new 24-homoscalaranes, lendenfeldaranes A&ndash, D (1&ndash, 4), along with three known compounds, 12&alpha, acetoxy-22-hydroxy-24-methyl-24-oxoscalar-16-en- 25-al (5), felixin F (6), and 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (7) were isolated from the sponge Lendenfeldia sp. The structures of scalaranes 1&ndash, 7 were elucidated on the basis of spectroscopic analysis. Scalaranes 1&ndash, 7 were further evaluated for their cytotoxicity toward a series of human cancer cell lines and the results suggested that 5 and 7 dominated in the anti- proliferative activity of the extract. The 18-aldehyde functionality was found to play a key role in their activity.

Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid β-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.

Two color laser pulses are used to form an air plasma and generate broadband infrared radiation suitable as a seed for backward Raman amplification of CO2 laser pulses. Broadband radiation in the atmospheric window from 8-14 microns is observed. The infrared radiation is characterized using a long wavelength grating spectrometer specially designed to accept an ionizing laser filament at its input plane. The LWIR yield is greatly enhanced by chirping the drive pulse. Unidirectional pulse propagation simulations suggest that this is due in part to the dependence of the nonlinear refractive index on the pulse duration., Comment: 7 pages, 8 figures

Hepatitis C virus (HCV) NS3 protein possesses protease and helicase activities and is considered an oncoprotein in virus-derived hepatocellular carcinoma. The NS3-associated oncogenesis has been studied but not fully understood. In this study, we have identified novel interactions of the NS3 protein with DNA repair factors, Werner syndrome protein (WRN) and Ku70, in both an HCV subgenomic replicon system and Huh7 cells expressing NS3. HCV NS3 protein inhibits WRN-mediated DNA repair and reduces the repair efficiency of nonhomologous end joining. It interferes with Ku70 recruitment to the double-strand break sites and alters the nuclear distribution of WRN-Ku repair complex. In addition, WRN is a substrate of the NS3/4A protease; the level of WRN protein is regulated by both the proteasome degradation pathway and HCV NS3/4A protease activity. The dual role of HCV NS3 and NS3/4A proteins in regulating the function and expression level of the WRN protein intensifies the effect of impairment on DNA repair. This may lead to an accumulation of DNA mutations and genome instability and, eventually, tumor development. IMPORTANCE HCV infection is a worldwide problem of public health and a major contributor to hepatocellular carcinoma. The single-stranded RNA virus with RNA-dependent RNA polymerase experiences a high error rate and develops strategies to escape the immune system and hepatocarcinogenesis. Studies have revealed the involvement of HCV proteins in the impairment of DNA repair. The present study aimed to further elucidate mechanisms by which the viral NS3 protein impairs the repair of DNA damage. Our results clearly indicate that HCV NS3/4A protease targets WRN for degradation, and, at the same time, diminishes the repair efficiency of nonhomologous end joining by interfering with the recruitment of Ku protein to the DNA double-strand break sites. The study describes a novel mechanism by which the NS3 protein influences DNA repair and provides new insight into the molecular mechanism of HCV pathogenesis.

Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid β-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.

Emerging AI-enabled applications such as augmented/virtual reality (AR/VR) leverage multiple deep neural network (DNN) models for sub-tasks such as object detection, hand tracking, and so on. Because of the diversity of the sub-tasks, the layers within and across the DNN models are highly heterogeneous in operation and shape. Such layer heterogeneity is a challenge for a fixed dataflow accelerator (FDA) that employs a fixed dataflow on a single accelerator substrate since each layer prefers different dataflows (computation order and parallelization) and tile sizes. Reconfigurable DNN accelerators (RDAs) have been proposed to adapt their dataflows to diverse layers to address the challenge. However, the dataflow flexibility in RDAs is enabled at the area and energy costs of expensive hardware structures (switches, controller, etc.) and per-layer reconfiguration. Alternatively, this work proposes a new class of accelerators, heterogeneous dataflow accelerators (HDAs), which deploys multiple sub-accelerators each supporting a different dataflow. HDAs enable coarser-grained dataflow flexibility than RDAs with higher energy efficiency and lower area cost comparable to FDAs. To exploit such benefits, hardware resource partitioning across sub-accelerators and layer execution schedule need to be carefully optimized. Therefore, we also present Herald, which co-optimizes hardware partitioning and layer execution schedule. Using Herald on a suite of AR/VR and MLPerf workloads, we identify a promising HDA architecture, Maelstrom, which demonstrates 65.3% lower latency and 5.0% lower energy than the best FDAs and 22.0% lower energy at the cost of 20.7% higher latency than a state-of-the-art RDA. The results suggest that HDA is an alternative class of Pareto-optimal accelerators to RDA with strength in energy, which can be a better choice than RDAs depending on the use cases., This paper is accepted at HPCA 2021

In this study, an in vitro tyrosinase inhibition assay in combination with ultra performance liquid chromatography-orbitrap mass spectrometry (UPLC-orbitrap-MS) was developed for the rapid screening and identification of tyrosinase modulators from roots of Angelica keiskei. Of the 15 candidates considered, nine chalcones, xanthoangelols (1), B (2), D (3), E (4), G (5), H (6), 4-hydroxyderricin (7), xanthokeismin B (8) and (2E)-1-[4-hydroxy-2-(2-hydroxy-2-propanyl)-2,3-dihydro-1-benzofuran-7-yl]-3-(4-hydroxyphenyl)-2-propen-1-one (9), five coumarins, umbelliferone (10), selinidin (11), isopimpinellin (12), phellopterin (13) and xanthyletin (14), and one other compound, ashitabaol A (15), were distinguished between the test samples and the controls with statistical significance, and the structure of each compound was determined by comparing with in-house standards and the literature. Among these, six compounds, xanthoangelol (1), xanthoangelol D (3), xanthoangelol H (6), 4-hydroxyderricin (7), laserpitin (16) and isolaserpitin (17), were isolated from roots of A. keiskei. Of the compounds isolated, compounds 1, 7 and 16 were subjected to tyrosinase inhibitory assay, and the IC50 values were 15.87 ± 1.21, 60.14 ± 2.29 and >100 μM, respectively. The present study indicated that the combination of in vitro tyrosinase inhibition assay coupled with UPLC-MS/MS could be widely applied to the rapid screening of active substances from various natural resources.

The v-raf murine sarcoma viral homolog B1 (BRAF) inhibitor drug vemurafenib (PLX4032) is used to treat melanoma, however, epidemiological evidence reveals that it could cause cutaneous keratoacanthomas and squamous cell carcinoma in cancer patients with the most prevalent HRASQ61L mutation. In a two-stage skin carcinogenesis mouse model, the skin papillomas induced by 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) (DT) resemble the lesions in BRAF inhibitor-treated patients. In this study, we investigated the bioactivity of Mentha aquatica var. Kenting Water Mint essential oil (KWM-EO) against PDV cells, mouse keratinocytes bearing HRASQ61L mutation, and its effect on inhibiting papilloma formation in a two-stage skin carcinogenesis mouse model with or without PLX4032 co-treatment. Our results revealed that KWM-EO effectively attenuated cell viability, colony formation, and the invasive and migratory abilities of PDV cells. Induction of G2/M cell-cycle arrest and apoptosis in PDV cells was also observed. KWM-EO treatment significantly decreased the formation of cutaneous papilloma further induced by PLX4032 in DT mice (DTP). Immunohistochemistry analyses showed overexpression of keratin14 and COX-2 in DT and DTP skin were profoundly suppressed by KWM-EO treatment. This study demonstrates that KWM-EO has chemopreventive effects against PLX4032-induced cutaneous side-effects in a DMBA/TPA-induced two-stage carcinogenesis model and will be worth further exploration for possible application in melanoma patients.

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.

Time is generally conceptualized in terms of space as reflected in temporal-spatial metaphors. Two observation perspectives have been proposed in the front-back axis of the temporal-spatial metaphor. One is called "ego-moving perspective" and the other "time-moving perspective." They are used to represent different relative motion between time and the observer. Previous studies have demonstrated the psychological reality of both perspectives. They also provided evidence that emotion can influence a perspective choice. In general, a positive emotion tends to facilitate the adoption of ego-moving perspective, whereas, a negative emotion tends to promote the adoption of time-moving perspective. However, it is unclear how the motivational dimension of emotion might influence the preference. The current study aimed to address the question by identifying conditions in which emotional valence or motivational attribute affects the choice of time movement perspective. An ambiguous temporal question and a visualized time motion schema were adopted to probe participants' metaphorical representation of time when they were affected by emotion. Study 1 investigated how a future emotional event would affect participants' choice of the time movement perspective. The results showed that positive future events led to a higher propensity to adopt an ego-moving perspective compared with negative future events. Study 2 explored participants' tendency to choose time movement perspective for a vague or neutral future event, after they were induced into a particular emotional state. The results showed that when being in an emotional state of approach-motivation individuals were more likely to adopt an ego-moving perspective. In contrast, being in an emotional state of avoidance-motivation, individuals were more likely to take a time-moving perspective. Taken together, these results suggest that the emotional valence of future events can influence the choice of time movement perspectives; and the motivational dimension of present emotional states plays an important role when contemplating a neutral future event.

This paper presents Timeloop, an infrastructure for evaluating and exploring the architecture design space of deep neural network (DNN) accelerators. Timeloop uses a concise and unified representation of the key architecture and implementation attributes of DNN accelerators to describe a broad space of hardware topologies. It can then emulate those topologies to generate an accurate projection of performance and energy efficiency for a DNN workload through a mapper that finds the best way to schedule operations and stage data on the specified architecture. This enables fair comparisons across different architectures and makes DNN accelerator design more systematic. This paper describes Timeloop's underlying models and algorithms in detail and shows results from case studies enabled by Timeloop, which provide interesting insights into the current state of DNN architecture design. In particular, they reveal that dataflow and memory hierarchy co-design plays a critical role in optimizing energy efficiency. Also, there is currently still not a single architecture that achieves the best performance and energy efficiency across a diverse set of workloads due to flexibility and efficiency trade-offs. These results provide inspiration into possible directions for DNN accelerator research.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform β and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 β, γ, e, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

Most cancer cases are closely related to many risk factors such as environment and diets. Carcinogenesis may also be controlled by epigenetic regulation. Salvia miltiorrhiza Bunge (Danshen) is a common Chinese herbal medicine, and it has been reported that it has anti-cancer, anti-inflammatory, anti-coagulant, and anti-thrombotic activities. In this study, we studied the effect and epigenetic mechanisms of cryptotanshinone (CTS) and dihydrotanshinone (DHTS), the major active ingredients in Danshen, against human colorectal cancer HCT116 cells. The results showed that CTS and DHTS suppressed the proliferation of HCT116 cells for 72-hour treatment and induced mRNA and protein expressions of p21 and DLEC1. Pro-apoptosis proteins such as PARP, caspase-3, and caspase-9 are cleaved and activated in HCT116 cells treating CTS and DHTS. Moreover, CTS and DHTS also increased the protein levels of epigenetics regulating enzymes, including histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) in HCT116 cells. Therefore, it is suggested that CTS and DHTS may affect tumor suppressor genes, such as p21 and DLEC1, by regulating epigenetic mechanisms, which induce apoptosis of colorectal cancer HCT116 cells. Citation Format: Zheng-Yuan Su, Yu-Hsin Chen Chen, Tien-Yuan Wu. Cryptotanshinone and dihydrotanshinone epigenetically suppress human colorectal cancer cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2613.

The authors demonstrate the key role dataflows play in the optimization of energy efficiency for deep neural network (DNN) accelerators. By introducing a systematic approach to analyze the problem and a new dataflow, called Row-Stationary, which is up to 2.5 times more energy efficient than existing dataflows in processing a state-of-the-art DNN, this work provides guidelines for future DNN accelerator designs.

A facile route to the synthesis of γ-sulfonyl lactones 5 and β-sulfonyl styrenes 6 has been developed, achieving moderate to good yields via the (1) NaH mediated Michael addition of β-ketosulfones 3 and methyl acrylate in refluxing THF and (2) NaBH4 mediated stereoselective reduction/lactonization of δ-ketoesters 4 in boiling MeOH, or (3) boron trifluoride etherate mediated ring-opening of lactones 5 in MeOH at reflux.

Deep learning using convolutional neural networks (CNN) gives state-of-the-art accuracy on many computer vision tasks (e.g. object detection, recognition, segmentation). Convolutions account for over 90% of the processing in CNNs for both inference/testing and training, and fully convolutional networks are increasingly being used. To achieve state-of-the-art accuracy requires CNNs with not only a larger number of layers, but also millions of filters weights, and varying shapes (i.e. filter sizes, number of filters, number of channels) as shown in Fig. 14.5.1. For instance, AlexNet [1] uses 2.3 million weights (4.6MB of storage) and requires 666 million MACs per 227×227 image (13kMACs/pixel). VGG16 [2] uses 14.7 million weights (29.4MB of storage) and requires 15.3 billion MACs per 224×224 image (306kMACs/pixel). The large number of filter weights and channels results in substantial data movement, which consumes significant energy., United States. Defense Advanced Research Projects Agency (DARPA YFA grant N66001-14-1-4039), Intel Corporation, Massachusetts Institute of Technology. Center for Integrated Circuits and Systems

Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.

The aim of this study was to investigate the effect of nonylphenol (NP), a widely used surfactant, on the reproductive performance of male Brown Tsaiya ducks (Anas platyrhynchos) (MBBTDs). Mature MBBTDs (n=100) were treated with NP by daily gavaging of 0, 1 (NP1), 10 (NP10) and 250 (NP250) mg/kg-BW/d for 14 wk. Semen quality, fertilization rate and specific factors in blood plasma were measured. Weights of organs were also measured at 14 wk after NP administration. Ducks from each treatment (n=4) were continually treated with NP thereafter for 12 mo to observe changes of tissue ultrastructure by microscopic examination. The results showed that ducks treated with amounts of NP of greater than 1mg NP/kg BW/d (NP1) for 14 wk had decreased sperm viability (32.3%) compared to those in the control group (74.1%, P0.05). The fertilization rate of ducks treated with 250mg NP/kg-BW/d (NP250) for 14 wk was reduced (21.0%) compared to the control group (74.5%, P0.05). Plasma aminotransferase (AST) and alanine aminotransferase (ALT) activities were also greater in NP250 group at the 14th wk post-treatment. Plasma testosterone concentrations were increased by NP1 treatment at the 14th wk post-treatment. Administration at dosage 250mg NP/kg-BW/d for 12 mo resulted in reduced sperm counts (P0.05) and histopathological changes, such as dilated seminiferous tubules (P0.05) and degenerated spermatocytes (P0.05). These findings strongly suggest that NP adversely affects the reproductive performance of MBBTDs.

Hypercholesterolemia is a common metabolic syndrome in modern human society. Despite that the alteration of host gut microbiota has been linked to hypercholesterolemia in previous studies, the key host-microbiota interaction of hypercholesterolemia remains elusive. Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) and deep sea water (DSW) were known for cholesterol-lowering potential. The impact of NTU 101 and DSW on hamster gut microbiota was investigated side-by-side using denaturing gradient gel electrophoresis (DGGE) and metagenomic analysis in this study. These two cholesterol-lowering substances altered hamster cecal microbiota in a very different way with similar cholesterol-lowering effects. Bacteroidetes was the only bacterial population that significantly correlated to host lipid profile (serum total cholesterol and serum low-density lipoprotein). Allobaculum and Clostridium XIVa were associated with beneficial effect of NTU 101. Parasutterella was only associated with consumption of DSW. The major bacterial taxa Akkermansia is associated with high-cholesterol diet but not host cholesterol level. This phenomenon suggested that cholesterol-lowering effect is not necessarily linked to specific bacteria-host interaction, and the conclusion of causal relationships among bacterial abundance, diet, and host physiology should be more rigorously investigated.

Columnaristerol A ( 1 ), a rare natural 19-norsterol possessing a 10β-hydroxy group was isolated from the Formosan octocoral Nephthea columnaris , and its structure was elucidated by spectroscopic methods. Sterol 1 was found to be a cytotoxic agent that exhibited in vitro moderate cytotoxic activity against MOLT-4 and SUP-T1 human leukemia–lymphoma cell lines.

Two new eunicellin-type diterpenoids, cladieunicellins R ( 1 ) and S ( 2 ), were isolated from the octocoral Cladiella tuberculosa and their structures were elucidated by spectroscopic methods. Eunicellin 1 was proven to be the first 2,6-hemiketal eunicellin and 2 was found to exhibit moderate cytotoxicity toward the MOLT-4, K562, and SUP-T1 cells.

Tin triflate-promoted one-pot intramolecular annulation of α-geranyl or α-farnesyl β-ketosulfones 3–4 affords the respective bicyclic or tricyclic sulfonyl dihydropyrans 5–6 in moderate to good yields via a cascade cation-olefin-carbonyl carbocyclization process. The starting materials 3 and 4 were obtained by K2CO3-mediated α-geranylation or α-farnesylation of β-ketosulfones 1 with bromides 2a or 2b. The structures of the key products were confirmed by X-ray crystallography.

In this work, we extend the split previously developed kinetic energy (dubbed as KEP) method Mineo and Chao (2012) by modifying the mass parameter to include the negative mass. We first show how to separate the total system into the subsystems with 3 attractive delta potentials by using the KEP method. For repulsive delta potentials, we introduce "negative" mass terms. Two cases are demonstrated using the "negative" mass terms for repulsive delta potential problems in quantum mechanics. Our work shows that the KEP solution scheme can be used to obtain not only the exact energies but also the exact wavefuctions very precisely.

Eight new briarane diterpenoids, designated briarenolides M–T (1–8), were isolated from an octocoral identified as Briareum sp. The structures of briaranes 1–8 were established by spectroscopic methods and by comparison of the spectroscopic data with those of known analogues. The relationship between 1H and 13C NMR chemical shifts of 2-hydroxybriaranes possessing of (A) a Δ3,5(16)-conjugated diene moiety or (B) a Δ3,5-conjugated diene moiety are described. Briarenolides M (1), P (4), S (7), and T (8) were found to inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein and briarenolides N (2), P (4), and T (8) were found to inhibit the accumulation of the pro-inflammatory cyclooxygenase-2 (COX-2) protein in LPS (lipopolysaccharide)-stimulated RAW264.7 macrophage cells.

Meter-scale nonlinear propagation of a picosecond ultraviolet laser beam in water, sufficiently intense to cause stimulated Raman scattering (SRS), nonlinear focusing, pump-Stokes nonlinear coupling, and photoexcitation, was characterized in experiments and simulations. Pump and SRS Stokes pulse energies were measured, and pump beam profiles were imaged at propagation distances up to 100 cm for a range of laser power below and above self-focusing critical power. Simulations with conduction band excitation energy U C B = 9.5 e V , effective electron mass m e f f = 0.2 m e , Kerr nonlinear refractive index n 2 = 5 × 10 − 16 c m 2 / W , and index contribution due to SRS susceptibility n 2 r = 1.7 × 10 − 16 c m 2 / W produced the best agreement with experimental data.

A natural caulerpenyne-derived sesquiterpene, oxytoxin-2 (1), was isolated from a cultured mollusc Volvatella vigourouxi. The structure of 1 was elucidated on the basis of spectroscopic analysis and this compound was suggested to be a diet-derived metabolite from the green alga Caulerpa sertularioides.-This is the first study on the chemical constituents of V. vigourouxi. Oxytoxin-2 (1) was found to inhibit significantly the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.

We propose to compress a high-energy, picosecond long-wave infrared (LWIR) pulse in the plasma using backward Raman amplification (BRA). The apparatus is in a counter-propagating geometry that employs a 3 J, 3 ps CO 2 laser pulse as the pump, and a microjoule, broadband femtosecond source as the seed. Simulations show that the amplified pulse can reach ~ 5 TW with a pulse duration of ~ 100 fs. Compared with earlier near-infrared BRA experiments, the proposed configuration uses a significantly shorter pump pulse duration, which may reduce limiting factors such as ion motions and Raman forward scattering. The experiment will be carried out at Accelerator Test Facility at Brookhaven National Laboratory.

Here we summarize the work presented during Working Group 6, Laser-Plasma Acceleration of Ions, at the 18th Advanced Accelerator Concepts Workshop in 2018.