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Consumption of Lactiplantibacillus plantarum TWK10 (TWK10) has beneficial probiotic effects, improves exercise endurance performance, regulates body composition, and mitigates aging‐related problems in mice and humans. Here, we investigated the effects of heat‐killed TWK10 on exercise endurance performance, muscle weight and strength, fatigue, and body composition in a double‐blind, placebo‐controlled clinical trial. Thirty healthy males aged 20–40 years were assigned to the Control group or heat‐killed TWK10 group (TWK10‐HK) in a balanced order according to each individual's initial maximal oxygen uptake. After 6‐week administration, the exercise endurance time in the TWK10‐HK was significantly increased (p = 0.0028) compared with that in the Control group. The grip strength on the right and left hands of the subjects was significantly increased (p = 0.0002 and p = 0.0140, respectively) in the TWK10‐HK compared with that in the Control group. Administration of heat‐killed TWK10 resulted in a significant increase (p = 0.0275) in muscle weight. After 6‐week administration, serum lactate, and ammonia levels were significantly lower in the TWK10‐HK group than in the Control group during the exercise and recovery periods. These findings demonstrate that heat‐killed TWK10 has significant potential to be used as a postbiotic for humans. [ABSTRACT FROM AUTHOR]

Metasurface operating in the transmission scheme has shown a promising scenario for flat optics applications. Nevertheless, the inherently low working efficiency of transmissive plasmonic metasurfaces at optical frequencies severely hinders them from future technology development. This work reports on a hybrid plasmonic meta‐atom (HPMA) with a simple fabrication and cost‐effective single‐lithographic process featuring a toroidal‐assisted generalized Huygens' source with a state‐of‐the‐art circular polarization conversion efficiency beyond 50%. The HPMA representsa new upper limit for transmission efficiency in the near‐infrared. The high transmission is realized via balanced multipoles of different orders including toroidal dipole that satisfies the generalized Kerker condition. The introduction of toroidal dipole provides an additional degree of freedom to tailor the wave interference and radiation symmetry rather than the use of a conventional electric and magnetic multipolar coupling. In addition, two high‐performance metasurfaces by combining the HPMAs with the geometric phase method are highlighted. The highly‐transmissive beam deflection metasurface and plasmonic metalens respectively yield anomalous refraction with 38.2% optical efficiency and 46.56% focusing efficiency, both experimentally showing a record transmission level. The findings may open new ways to design highly‐efficient plasmonic metasurfaces and to take one step forward to facilitate nearly optimal and practical nanophotonic devices. [ABSTRACT FROM AUTHOR]

Grain size and weight are the key traits determining rice quality and yield and are mainly controlled by quantitative trait loci (QTL). In this study, one minor QTL that was previously mapped in the marker interval of JD1009-JD1019 using the Huanghuazhan/Jizi1560 (HHZ/JZ1560) recombinant inbred line (RIL) population, qTGW1-2, was validated to regulate grain size and weight across four rice-growing seasons using twenty-one near isogenic line (NIL)-F2 populations. The twenty-one populations were in two types of genetic background that were derived from the same parents HHZ and JZ1560. Twelve F9, F10 or F11 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were developed from one residual heterozygote (RH) in the HHZ/JZ1560 RIL population, and the remaining nine BC3F3, BC3F4 or BC3F5 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were constructed through consecutive backcrosses to the recurrent parent HHZ followed with marker assistant selection in each generation. Based on the QTL analysis of these genetic populations, qTGW1-2 was successfully confirmed to control grain length, width and weight and further dissected into two QTLs, qTGW1-2a and qTGW1-2b, which were respectively narrowed down to the marker intervals of JD1139-JD1127 (~ 978.2-kb) and JD1121-JD1102 (~ 54.8-kb). Furthermore, the two types of NIL-F2 populations were proved to be able to decrease the genetic background noise and increase the detection power of minor QTL. These results provided an important basis for further map-based cloning and molecular design breeding with the two QTLs in rice. [ABSTRACT FROM AUTHOR]

Two distinct mechanisms for primordial germ cell (PGC) specification are observed within Bilatera: early determination by maternal factors or late induction by zygotic cues. Here we investigate the molecular basis for PGC specification in Nematostella, a representative pre-bilaterian animal where PGCs arise as paired endomesodermal cell clusters during early development. We first present evidence that the putative PGCs delaminate from the endomesoderm upon feeding, migrate into the gonad primordia, and mature into germ cells. We then show that the PGC clusters arise at the interface between hedgehog1 and patched domains in the developing mesenteries and use gene knockdown, knockout and inhibitor experiments to demonstrate that Hh signaling is required for both PGC specification and general endomesodermal patterning. These results provide evidence that the Nematostella germline is specified by inductive signals rather than maternal factors, and support the existence of zygotically-induced PGCs in the eumetazoan common ancestor. [ABSTRACT FROM AUTHOR]

Preterm labor is associated with inflammation and infection. The mechanisms underlying the role of omega-3 fatty acid in inflammasome activation and prevention of preterm labor remain unknown. We hypothesized that omega-3 fatty acid can reduce the rate of preterm birth induced by infection and trophoblast inflammation. In the present study, we found that inflammasome-related molecules and IL-1β in trophoblasts were activated by TNF-α derived from lipopolysaccharide (LPS)-stimulated THP-1 cell-conditioned medium (CM) and recombinant TNF-α protein. The results demonstrated that stimulation with TNF-α caused lysosomal rupture in trophoblasts, which accelerated cathepsin S (CTSS) diffusion from lysosomes to the cytosol and activated NLRP1 (nacht domain-leucine-rich repeat, and pyd-containing protein 1) and absent in melanoma 2 (AIM2) inflammasomes, thereby increasing IL-1β secretion. Moreover, in response to LPS challenge, TNF-α increased trophoblast cell death and decreased cell viability through inflammasome and CTSS activation. Stearidonic acid (SDA; 18:4n-3) and docosahexaenoic acid (DHA; 22:6n-3) inhibited inflammasome-related molecule synthesis and CTSS and caspase-1 activation, which further reduced the preterm delivery rate of pregnant mice induced by LPS (92.9 compared with 69.7% (DHA); 92.9 compared with 53.5% (SDA)). Higher expression of TNF-α, IL-1β, prostaglandin E2, and CTSS, but lower resolvin D1 expression, was observed in preterm pregnant mice than in controls. Similarly, resolvin D1 was highly expressed in women with term delivery compared with women with preterm delivery. Thus, SDA and DHA may attenuate macrophage-derived TNF-α inducing CTSS and inflammasome activation, IL-1β secretion, and placental trophoblast cell death. These functions are implicated in the preventive effects of SDA and DHA on preterm labor. [ABSTRACT FROM AUTHOR]

This study compares supercapacitors with reduced graphene oxide (rGO)‑carbon black (CB) and CB nanocomposite coated carbon cloth electrodes. We use a nitrogen DC-pulse atmospheric pressure plasma jet (APPJ) to process the electrodes. The APPJ processing time is <40 s. Nitrogen APPJ burns off organic binders to create nanoporous structures. Replacing part of the CB with rGO nano-flakes can increase the overall surface area to improve the supercapacitive performance. Specifically, by replacing 50 wt% of CBs with rGOs, the specific (areal) capacitance can be improved from 91.84 F·g −1 (19.74 mF/cm 2 ) to 162.68 F·g −1 (29.16 mF/cm 2 ), respectively, with 20 s APPJ processing time, as evaluated by cyclic voltammetry under a potential scan rate of 2 mV·s −1 . The nitrogen DC-pulse APPJ is demonstrated to be an ultrafast and highly economical tool for efficiently processing nanocomposite electrodes of supercapacitors. [ABSTRACT FROM AUTHOR]

An efficient, one-pot and metal-free process for the preparation of 3,5-disubstituted and 3,4,5-trisubstituted pyrazoles on multigram scale was developed. One-pot condensation of ketones, aldehydes and hydrazine monohydrochloride readily formed pyrazoline intermediates under mild conditions. Oxidation of pyrazolines, in situ, employing bromine afforded a wide variety of pyrazoles. The methodology offers a fast, and often chromatography-free protocol for the synthesis of 3,4,5- substituted pyrazoles in good to excellent yields. Alternatively, a more benign oxidation protocol affords 3,5-disubstituted or 3,4,5-trisubstituted pyrazoles by simply heating pyrazolines in DMSO under oxyg [ABSTRACT FROM AUTHOR]

An efficient synthesis of quinazolines based on an iron-catalyzed C(sp³)-H oxidation and intramolecular C-N bond formation using tert-BuOOH as the terminal oxidant is described. The reaction of readily available 2-alkylamino benzonitriles with various organometallic reagents led to 2-alkylamino N-H ketimine species. The FeCl2-catalyzed C(sp³)-H oxidation of the alkyl group employing tert-BuOOH followed by intramolecular C-N bond formation and aromatization afforded a wide variety of 2,4-disubstituted quinazolines in good to excellent yields. [ABSTRACT FROM AUTHOR]

A facile synthesis of 1 -catalyzed N-N bond formation using oxygen as the terminal oxidant is described. The reaction of readily available 2-aminobenzonitriles with various organometallic reagents led to -aminoaryl N-H ketimine species. The subsequent Cu(OAc) -catalyzed N-N bond formation in DMSO under oxygen afforded a wide variety of 1 -indazoles in good to excellent yields. [ABSTRACT FROM AUTHOR]

The thyroid hormone, 3,3,5-triiodo-L-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development and pregnancy-related diseases. In particular, infection is the leading cause of neonatal mortality and morbidity worldwide. However, to date, no successful approach has been developed for the effective diagnosis of infection in preterm infants. Pre-eclampsia (PE) is a serious disorder that adversely affects ~5% of human pregnancies. Recent studies identified a multiprotein complex, the inflammasome, including the Nod-like receptor (NLR) family of cytosolic pattern recognition receptors, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, which plays a vital role in the placenta. The thyroid hormone modulates inflammation processes and is additionally implicated in placental development and disease. Therefore, elucidation of thyroid hormone receptor-regulated inflammation-related molecules, and their underlying mechanisms in placenta, should facilitate the identification of novel predictive and therapeutic targets for placental disorders. This review provides a detailed summary of current knowledge with respect to identification of useful biomarkers and their physiological significance in placenta. [ABSTRACT FROM AUTHOR]

A general and efficient asymmetric synthesis of cyclic indoline aminals was developed with a high level of 1,3-stereoinduction through a dynamic crystallization-driven condensation. Dehydrogenation of the indoline aminals with potassium permanganate produced the corresponding cyclic indole aminals in high yields and excellent enantioselectivities. This general methodology was successfully applied to the synthesis of a wide variety of chiral cyclic indoline aminals and indole aminals with aromatic and aliphatic functional groups. [ABSTRACT FROM AUTHOR]

Background The thyroid hormone, 3, 3',5-triiodo-L-thyronine (3), has been shown to modulate cellular processes via interactions with thyroid hormone receptors (TRs), but the secretory proteins that are regulated to exert these effects remain to be characterized. Brain-specific serine protease 4 (BSSP4), a member of the human serine protease family, participates in extracellular matrix remodeling. However, the physiological role and underlying mechanism of 3-mediated regulation of BSSP4 in hepatocellular carcinogenesis are yet to be established. Methods The thyroid hormone response element was identified by reporter and chromatin immunoprecipitation assays. The cell motility was analyzed via transwell and SCID mice. The BSSP4 expression in clinical specimens was examined by Western blot and quantitative reverse transcription polymerase chain reaction. Results Upregulation of BSSP4 at mRNA and protein levels after 3 stimulation is a time- and dose-dependent manner in hepatoma cell lines. Additionally, the regulatory region of the BSSP4 promoter stimulated by 3 was identified at positions -609/-594. BSSP4 overexpression enhanced tumor cell migration and invasion, both in vitro and in vivo. Subsequently, BSSP4-induced migration occurs through the ERK 1/2-C/EBPβ-VEGF cascade, similar to that observed in HepG2-TRα1 and J7-TRα1 cells. BSSP4 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively associated with TRα1 and VEGF to a significant extent. Importantly, a mild association between BSSP4 expression and distant metastasis was observed. Background The thyroid hormone, 3, 3',5-triiodo-L-thyronine (3), has been shown to modulate cellular processes via interactions with thyroid hormone receptors (TRs), but the secretory proteins that are regulated to exert these effects remain to be characterized. Brain-specific serine protease 4 (BSSP4), a member of the human serine protease family, participates in extracellular matrix remodeling. However, the physiological role and underlying mechanism of 3-mediated regulation of BSSP4 in hepatocellular carcinogenesis are yet to be established. Methods The thyroid hormone response element was identified by reporter and chromatin immunoprecipitation assays. The cell motility was analyzed via transwell and SCID mice. The BSSP4 expression in clinical specimens was examined by Western blot and quantitative reverse transcription polymerase chain reaction. Results Upregulation of BSSP4 at mRNA and protein levels after 3 stimulation is a time- and dose-dependent manner in hepatoma cell lines. Additionally, the regulatory region of the BSSP4 promoter stimulated by 3 was identified at positions -609/-594. BSSP4 overexpression enhanced tumor cell migration and invasion, both in vitro and in vivo. Subsequently, BSSP4-induced migration occurs through the ERK 1/2-C/EBPβ-VEGF cascade, similar to that observed in HepG2-TRα1 and J7-TRα1 cells. BSSP4 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively associated with TRα1 and VEGF to a significant extent. Importantly, a mild association between BSSP4 expression and distant metastasis was observed. Conclusions Our findings collectively support a potential role of T3 in cancer cell progression through regulation of the BSSP4 protease via the ERK 1/2-C/EBPβ-VEGF cascade. BSSP4 may thus be effectively utilized as a novel marker and anti-cancer therapeutic target in HCC. [ABSTRACT FROM AUTHOR]

Thyroid hormones (THs) are potent mediators of several physiological processes, including embryonic development, cellular differentiation, metabolism, and cell growth. Triiodothyronine (T3) is the most biologically active TH form. Thyroid hormone receptors (TRs) belong to the nuclear receptor superfamily and mediate the biological functions of T3 via transcriptional regulation. TRs generally form heterodimers with the retinoid X receptor (RXR) and regulate target genes upon T3 stimulation. Research over the past few decades has revealed that disruption of cellular TH signaling triggers chronic liver diseases, including alcoholic or nonalcoholic fatty liver disease and hepatocellular carcinoma (HCC). Animal model experiments and epidemiologic studies to date imply close associations between high TH levels and prevention of liver disease. Moreover, several investigations spanning four decades have reported the therapeutic potential of T3 analogs in lowering lipids, preventing chronic liver disease, and as anticancer agents. Thus, elucidating downstream genes/signaling pathways and molecular mechanisms of TH actions is critical for the treatment of significant public health issues. Here, we have reviewed recent studies focusing on the roles of THs and TRs in several disorders, in particular, liver diseases. We also discuss the potential therapeutic applications of THs and underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M. [ABSTRACT FROM AUTHOR]

A divergent and regioselective synthesis of either 3-substituted benzisoxazoles or 2-substituted benzoxazoles from readily accessible ortho-hydroxyaryl N–H ketimines is described. The reaction proceeds in two distinct pathways through a common N–Cl imine intermediate: (a) N–O bond formation to form benzisoxazole under anhydrous conditions and (b) NaOCl mediated Beckmann-type rearrangement to form benzoxazole, respectively. The reaction path also depends on the electronic nature of the aromatic ring, with the electron-rich aromatic rings favoring the rearrangement and the electron-deficient rings favoring the N–O bond formation. A Beckmann-type rearrangement mechanism vianet [1,2]-aryl migration for the formation of 2-substituted benzoxazole is proposed. [ABSTRACT FROM AUTHOR]

A highly efficient and straightforward protocol to prepare carbamates from alcohols and hindered amino acids/esters mediated by N,N'-disuccinimidyl carbonate (DSC) in the presence of catalytic amount of pyridine is described. This method could be carried out under mild conditions in one pot, and a wide variety of carbamates were obtained in high yield with excellent purity. [ABSTRACT FROM AUTHOR]

A controlled regioselective synthesis of either C-2 or C-3 substituted benzo[b]furans from readily accessible 1-(2-hydroxyphenyl)-2-chloroethanones is described. Addition of a range of Grignard reagents to the α-chloro ketones generates alkoxide intermediates, which can form either 2-substituted benzo[b]furans via a [1,2]-aryl migration or 3-substituted benzo[b]furans via a direct cyclization and dehydration sequence. A temperature-dependent [1,2]-aryl migration mechanism for the formation of 2-substituted benzo[b]furan is proposed. [ABSTRACT FROM AUTHOR]

The cycloacylation of aniline derivatives to 4-quinolones in the presence of Eaton's reagent is described. This high-yielding methodology is applicable to a wide variety of functionalized anilines and requires milder conditions than those traditionally employed. This cyclization protocol is used to prepare a host of heterocycles and bis-quinolones and is characterized by relatively low reaction temperature and ease of product isolation. [ABSTRACT FROM AUTHOR]

A wide variety of benzo[b]furans were synthesized efficiently via a CuI-catalyzed ring closure of 2-haloaromatic ketones. The methodology was tolerant to various functional groups, affording benzofurans in 72–99% yields. [ABSTRACT FROM AUTHOR]

A practical, chromatography-free catalytic asymmetric synthesis of a potent and selective PDE4 inhibitor (L-869,298, 1) is described. Catalytic asymmetric hydrogenation of thiazole ketone 5a afforded the corresponding alcohol 3b in excellent enantioselectivity (up to 99.4% ee). Activation of alcohol 3b via formation of the corresponding p-toluenesulfonate followed by an unprecedented displacement with the lithium enolate of ethyl 3-pyridylacetate N-oxide 4a generated the required chiral trisubstituted methane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Conversion of esters 2b to I was accomplished via a one-pot deprotection, saponification, and decarboxylation sequence in excellent overall yield. [ABSTRACT FROM AUTHOR]

A large-scale, chromatography-free synthesis of a potent and selective Cathepsin K inhibitor I is reported. The key asymmetric center was installed by addition of (R)-pantolactone to the in situ generated ketene 4a. The final step of the convergent synthesis of 1 was completed via Suzuki coupling of aryl bromide 7a with unprotected aryl piperazine boronic acid 13. Residual palladium and iron generated in the Suzuki coupling were efficiently removed from crude I via a simple extractive workup using lactic acid. [ABSTRACT FROM AUTHOR]

Examines the syntheses of indoles through a palladium-catalyzed annulation between iodoanilines and ketones. Description of the Fischer indole reaction as the traditional approach for preparing indole nucleus; Importance of amine bases in coupling; Investigation of the generality of the palladium-catalyzed coupling reaction.

A straightforward synthesis of 1,3-disubstituted azetidines has been accomplished via the alkylation of a primary amine with the bis-triflate of a 2-substituted-1,3-propanediol species. This transformation is carried out in one reaction vessel, and elimination of the alkylating reagent is generally not a major byproduct. The scope of this methodology has been investigated using a variety 2-substituted-1,3-propanediols and amine nucleophiles. [ABSTRACT FROM AUTHOR]

• Rush order insertion to satisfy immediate customer demand with early delivery. • Stochastic hybrid flow shop network to construct a manufacturing system. • System reliability to evaluate the probability of meeting demand within time. • A practical case of suction cover manufacturing system is studied. Rush order (RO) insertion is a common problem in industrial plants and represents immediate customer demand characterized by early delivery requirements. Consequently, capacity prioritizes handling RO over processing general orders (GO). In a manufacturing system, the number of machines in a workstation can be influenced by factors, such as failure and maintenance, resulting in the stochastic capacity of each workstation. Considering the stochastic nature of the capacity state in a manufacturing system, this study models it as a stochastic hybrid flow shop (SHFS) network. Algorithms are proposed to generate the lowest capacity vectors (LCVs) that satisfy both the GO and RO. In particular, the proposed algorithms can be applied to an arbitrary capacity probability distribution of a workstation. To assess the system performance of the SHFS network, we employed network reliability as a performance metric to evaluate the possibility of meeting the demand within the specified time constraints in terms of LCVs. We consider GO and RO, each with different time constraints for completion. Numerical examples show that the network reliability indicates the capability of an SHFS to handle both GO and RO. Therefore, decision-makers can ensure that the capacity of the SHFS is sufficient to meet customer demand. [ABSTRACT FROM AUTHOR]

A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael-lactolization-dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps. [ABSTRACT FROM AUTHOR]

Chronic inflammation caused by liver damage or infection plays an important role in the development and progression of hepatocellular carcinoma (HCC). The activation of Toll-like receptors 4 (TLR4) is involved in HCC tumorigenesis. Moreover, high TLR4 expression in HCC has been linked to poor prognosis. Although the expression of TLR4 in HCC is relatively low compared to hematopoietic cells, it is important to explore the molecular mechanism leading to the elevation of TLR4 in HCC. In this study, we aimed to investigate the positive regulating loop for TLR4 expression in HCC in response to chronic inflammation. Our results confirm that the mRNA expression of TLR4 and proinflammatory cytokines, including interleukin 6 (IL6) and C-C motif chemokine ligand 2 (CCL2), positively correlate in human HCC samples. High TLR4 expression in HCC is more susceptible to lipopolysaccharide (LPS); TLR4 activation in HCC provides growth and survival advantages and thus promotes tumorigenesis. It has been shown that the LIN28/let-7 microRNA (miRNA) axis is a downstream effector of the TLR4 signal pathway, and let-7 miRNA is a potential post-transcriptional regulator for TLR4. Thus, we investigated the correlation between TLR4 and LIN28A mRNA and let-7g miRNA in HCC clinical samples and found that the expression of TLR4 was positively correlated with LIN28A and negatively correlated with let-7g miRNA. Moreover, by culturing PLC/PRF5 (PLC5) HCC cells in low-dose LPS-containing medium to mimic chronic inflammation for persistent TLR4 activation, the mRNA and protein levels of TLR4 and LIN28A were elevated, and let-7g miRNA was decreased. Furthermore, the 3' untranslated region (3'UTR) of TLR4 mRNA was shown to be the target of let-7g miRNA, suggesting that inhibition of let-7g miRNA is able to increase TLR4 mRNA. While parental PLC5 cells have a low susceptibility to LPS-induced cell growth, long-term LPS exposure for PLC5 cells leads to increased proliferation, cytokine expression and stemness properties. In conclusion, our studies demonstrate positive feedback regulation for chronic TLR4 activation in the modulation of TLR4 expression level through the LIN28A/let-7g pathway in HCC and suggest a connection between chronic inflammation and TLR4 expression level in HCC for promoting tumorigenesis. [ABSTRACT FROM AUTHOR]

A practicalasymmetric synthesis of the complex fused bis-macrocyclicHCV protease inhibitor MK-6325 (1) is described. Throughthe combination of a high yielding and low catalyst loading ring-closingmetathesis (RCM) to forge the 15-membered macrocycle with an intramolecular sp2–sp3Suzuki–Miyauracross-coupling to append the 18-membered macrocycle, multikilogramaccess to the unique and challenging architecture of MK-6325 (1) has been achieved. [ABSTRACT FROM AUTHOR]

A general approach for the synthesis of 3,5-diarylcyclopen- tenones was developed. Key aspects of this approach are the intramolecular Friedel-Crafts-type cyclization of vinyl chlorides and subsequent Pd-catalyzed cross-coupling reac- tions. The requisite vinyl chloride-bearing arylacetic acid precursors are readily available by straightforward alkylation of arylacetic acid esters and undergo cyclization to yield 3-chloro-5-aryl-2-cyclopentenones when treated with AId3. The vinylogous acid chloride functionality present in these immediate products allows for further elaboration via Pd-catalyzed cross-coupling chemistry, leading to a diverse array of products. [ABSTRACT FROM AUTHOR]

In this study, two different thin films, TiO2 thin film and TiO2–W–TiO2 multi-layer thin films (W, tungsten), are prepared by RF magnetron sputtering onto glass substrates. The crystal structure, morphology, and transmittance of TiO2 and TiO2–W–TiO2 multi-layer thin films are investigated by X-ray diffraction, SEM, and UV-Vis spectrometer, respectively. The amorphous, rutile, and anatase TiO2 phases are observed in the TiO2 thin film and in the TiO2–W–TiO2 multi-layer thin films. The deposition of tungsten as the inter-layer will have large effect on the transmittance and phase ratios of rutile and anatase phases in the TiO2–W–TiO2 multi-layer thin films. The crystal intensities of amorous TiO2 will decrease as the tungsten is used as the middle layer in the multi-layer structure. The band gap energy values of TiO2 thin film and TiO2–W–TiO2 multi-layer thin films are evaluated from ( αh ν)1/2 versus energy plots, and the calculated results show that the energy gap decreases from 3.21 eV (TiO2 thin film) to 3.08∼3.03 EV (TiO2–W–TiO2 multi-layer thin films). [ABSTRACT FROM AUTHOR]

A modular approach for the regiocontrolled preparation of pyrazoles bearing substituents on all three carbon atoms is described. Central to this method is the use of a switchable metal-directing group (MDG) to enable sequential direct lithiation of the 3- and 5-positions of the pyrazole ring. Pyrazole boronic esters obtained from these lithiated intermediates can undergo efficient Suzuki cross-coupling under the developed nonaqueous conditions, which minimize undesirable protolytic deboronation. Halogenation of the 4-position provides the means for substitution at the remaining carbon atom. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, the effects of ozone exposure on enterovirus 71 (EV71) replication and related cytokine production were investigated. Rhabdomyosarcoma cells (RD) were exposed to 0.5, 1, 1.5 and 2ppm ozone or filtered air under different exposure regimens before or after infection for 1 or 2h. The results revealed that at a proper concentration of ozone, e.g., 1.5 or 2ppm, ozone exposure restricted virus production, prolonged survival time of cells and modulated cytokine production related to EV71 infection. Upon exposure of non-infected cells to ozone at 1.5 or 2ppm for 1h, the production of IL-1β, IL-6 and TNF-α was primed and boosted by the subsequent EV71 infection, generating an inhibitory effect on EV71 replication during the post-infection period of 48h. While infected cells were exposed to ozone for 2h at 1.5 or 2ppm, ozone did not affect cytokine production by RD cells in response to EV71 infection. The data showed that ozone effect on induction of cytokine was only found in uninfected cells. The ozone-induced cytokines produced prior to the onset of EV71 infection generated antiviral effects, which proved beneficial in suppressing the subsequent EV71 infection. [Copyright &y& Elsevier]

Deals with a study which characterized a hospitalwide nosocomial infection outbreak in Taipei, Taiwan due to pandrug-resistant Acinetobacter baumannii by investigating antibiotypes and genotypes by pulsed field gel electrophoresis and arbitrarily primed polymerase chain reaction. Methods; Results; Discussion.

The stereospecific cross-coupling of enantioenriched nonbenzylic secondary alkyl boron compounds has been achieved. The high selectivity toward product formation over an undesired β-H elimination pathway is achieved via an intramolecular coordination of an ancillary carbonyl to the metal center in the diorganopalladium intermediate. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play an important role to contribute carcinogenesis. The aim of the current study was to identify useful biomarkers from miRNAs. Differential miRNA profiles were analyzed using the miRNA qRT-PCR-based assay. Two of the most upregulated miRNAs were selected and validated. The miR-196a/-196b levels were significantly increased in gastric cancer (GC) tissues (n = 109). Overexpression of miR-196a/-196b was significantly associated with tumor progression and poorer 5-year survival outcomes. Overexpression of miR-196a/-196b enhances GC cell migration and invasion. Further, radixin was identified as a target gene of miR-196a/-196b. Elevated miR-196a/-196b expression in GC cells led to reduced radixin protein levels and vice versa. Notably, an inverse correlation between miR-196a/-196b and radixin mRNA and protein expression was observed in GC tissues with in situ hybridization and immunohistochemistry analyses. Together, miR-196a/-196b inhibitory oligonucleotides or overexpression of the radixin may thus have therapeutic potential in suppressing GC metastasis. [ABSTRACT FROM AUTHOR]

A new type of balun-bandpass filter was proposed based on the traditional coupled-line theory and folded open-loop ring resonators (OLRRs) configuration. For that, a new device with both filter-type and balun-type characteristics was investigated and fabricated. Both magnetic and electric coupling structures were implemented to provide high performance balun-band pass responses. The fabricated balun-bandpass filters had a wide bandwidth more than 200MHz and a low insertion loss less than 2.51 dB at a center frequency of 2.6GHz. The differences between the two outputs were below 0.4 dB in magnitude and within 180 ± 7°in phase. Also, the balun-bandpass filter presented an excellent common-mode rejection ratio over 25 dB in the passband. An advanced design methodology had been adopted based on EM simulation for making these designed parameters of OLRRs, microstrip lines, and open stubs. The measured frequency responses agreed well with simulated ones. [ABSTRACT FROM AUTHOR]

Thyroid hormone (T3) signaling through the thyroid hormone receptor (TRα1) regulates hepatoma cell growth and pathophysiology, but the underlying mechanisms are unclear at present. Here, we have shown that the oncomir microRNA-21 (miR-21) is activated by T3 through a native T3 response element in the primary miR-21 promoter. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T3 stimulation in hepatoma cells. In addition, anti-miR-21-induced suppression of cell migration was rescued by T3. The Rac-controlled regulator of invasion and metastasis, T-cell lymphoma invasion and metastasis 1 (TIAM1), was identified as a miR-21 target additionally downregulated by T3. Attenuation and overexpression of miR-21 induced upregulation and downregulation of TIAM1, respectively. TIAM1 attenuation, in turn, enhanced migration and invasion via the upregulation of β-catenin, vimentin, and matrix metalloproteinase-2 in hepatoma cells. Notably, correlations between TRα1, miR-21, and TIAM1 expression patterns in animal models paralleled those observed in vitro. In the clinic, we observed a positive correlation (P = 0.005) between the tumor/nontumor ratios of TRα1 and miR-21 expression, whereas a negative correlation (P = 0.019) was seen between miR-21 and TIAM1 expression in patients with hepatoma. Our findings collectively indicate that miR-21 stimulation by T3 and subsequent TIAM1 suppression promotes hepatoma cell migration and invasion. [ABSTRACT FROM AUTHOR]

A general method for the preparation of α-hydroxyacetophenones is presented. Functionalized arylmagnesium species are transmetalated to the corresponding arylzinc intermediates, which undergo Cu(I)-catalyzed reaction with acetoxyacetyl chloride. Acidic hydrolysis of the acetate group releases the target α-hydroxyacetophenones with minimal production of undesired polymeric degradates that are often observed under alternative conditions. [ABSTRACT FROM AUTHOR]

Glyoxalase I (GLO1), a methylglyoxal detoxification enzyme, is implicated in the progression of human malignancies. The role of GLO1 in gastric cancer development or progression is currently unclear. The expression of GLO1 was determined in primary gastric cancer specimens using quantitative polymerase chain reaction, immunohistochemistry (IHC), and western blotting analyses. GLO1 expression was higher in gastric cancer tissues, compared with that in adjacent noncancerous tissues. Elevated expression of GLO1 was significantly associated with gastric wall invasion, lymph node metastasis, and pathological stage, suggesting a novel role of GLO1 in gastric cancer development and progression. The 5-year survival rate of the lower GLO1 expression groups was significantly greater than that of the higher expression groups (log rank P = 0.0373) in IHC experiments. Over-expression of GLO1 in gastric cancer cell lines increases cell proliferation, migration and invasiveness. Conversely, down-regulation of GLO1 with shRNA led to a marked reduction in the migration and invasion abilities. Our data strongly suggest that high expression of GLO1 in gastric cancer enhances the metastasis ability of tumor cells in vitro and in vivo, and support its efficacy as a potential marker for the detection and prognosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Treatment of ω-epoxynitriles with hydroxylamine affords cyclic aminonitrones in a single step and with high stereoselectivity. The scope of this novel transformation was explored in a series of examples. The aminonitrone products were shown to be useful substrates for further selective elaboration. [ABSTRACT FROM AUTHOR]

A short and practical synthesis of glucokinase activator 1 was achieved utilizing a convergent strategy involving SNAr coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of α-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound 1 in a 31% overall yield over six steps. [ABSTRACT FROM AUTHOR]

A mild and transition-metal-free method for the α-arylation of aliphatic nitriles with activated heteroaryl halides was developed using NaHMDS or KHMDS as base at ambient temperature. The key to the success of this method is generation of the nitrile anion in the presence of the hetoroaryl halide. The method is applicable to both primary and secondary carbonitriles and a wide range of heteroaryl halides. Selective monoarylation was observed with primary carbonitriles. The operational simplicity and the mild reaction conditions add to the value of this method as a practical alternative to the preparation of α-hetoroaryl carbonitriles. [ABSTRACT FROM AUTHOR]

The waxy (Wx) gene, encoding the granule-bound starch synthase (GBSS), is responsible for amylose biosynthesis and plays a crucial role in defining eating and cooking quality. The waxy locus controls both the non-waxy and waxy rice phenotypes. Rice starch can be altered into various forms by either reducing or increasing the amylose content, depending on consumer preference and region. Low-amylose rice is preferred by consumers because of its softness and sticky appearance. A better way of improving crops other than downregulation and overexpression of a gene or genes may be achieved through the posttranslational modification of sites or regulatory enzymes that regulate them because of their significance. The impact of posttranslational GBSSI modifications on extra-long unit chains (ELCs) remains largely unknown. Numerous studies have been reported on different crops, such as wheat, maize, and barley, but the rice starch granule proteome remains largely unknown. There is a need to improve the yield of low-amylose rice by employing posttranslational modification of Wx, since the market demand is increasing every day in order to meet the market demand for low-amylose rice in the regional area that prefers low-amylose rice, particularly in China. In this review, we have conducted an in-depth review of waxy rice, starch properties, starch biosynthesis, and posttranslational modification of waxy protein to genetically improve starch quality in rice grains. [ABSTRACT FROM AUTHOR]

The article reports on the enantioselective arylation of N-Boc-pyrrolidine to develop an effective asymmetric structures of biologically active compounds. It is noted that the palladium-catalyzed arylation of such chemical structures is the most efficient way to obtain enantioenriched 2-arylpyrrolidines.