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An unprecedented Pd-catalyzed asymmetric intramolecular cascade cyclization of aryl halides with readily available arylboronic acids proceeds through a Heck-type dearomative cyclization terminated with arylation in the presence of Pd2(dba)3 (10 mol %), Cu2O (5 mol %), and Cs2CO3 (2.0 equiv) in 1,2-dichloroethane (1.0 mL) at 100 °C for 15 h in air using BINOL-based phosphoramidite as the chiral ligand. This dearomative Heck protocol, which tolerates a broad variety of functional groups, is amenable to the generation of optically active indoline derivatives bearing all-carbon quaternary stereogenic centers in one step in moderate to excellent yields, with excellent diastereoselectivities (>20:1) and enantioselectivities (up to >99% ee). It is worth mentioning that no decrease in the enantiopurity of the indoline derivatives was observed during the synthetic transformations of the products.

A method based on QuEChERS (quick, easy, cheap, effective, rugged, and safe) sample preparation coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for determining 43 pesticide residues in strawberries. The clean-up sorbents were optimized, with 50 mg PSA + 50 mg C18 + 150 mg MgSO4 showing the best performance in d-SPE. The effect of injection volume on matrix effect (ME) was investigated. The proposed method had a linear range of 0.001–0.1 mg kg−1, and determination coefficients (R2) were greater than 0.995. Recoveries of the selected pesticides were 70.1–119.6% with relative standard deviations (RSD) at three concentrations (0.01, 0.05, and 0.1 mg kg−1) lower than 20%. The limit of quantification (LOQ) of the 43 pesticides was ≤ 0.005 mg kg−1. This method was applied to 80 strawberry samples collected from 8 villages in Beijing suburbs, and 12 pesticide residues were quantitatively detected with the concentrations ranging from 0.02 to 2.5 mg kg−1.

Disclosed herein is a cross-dehydrogenative-coupling reaction of N-heterocycles including 1,2,4-triazine-3,5(2H, 4H)-diones and quinoxaline-2(1H)-ones with N-methylanilines to form C(sp2)-C(sp3) under visible-light illumination and ambient air at room temperature. In this process, easily available Ru(bpy)3Cl2·6H2O serves as the catalyst, and air acts as the green oxidant. This method features high atom economy, environmental friendliness, and convenient operation and provides an efficient and practical access to aminomethyl-substituted N-heterocycles with extensive functional group compatibility in 40-86% yields.

Marine aquaculture in semi-enclosed bays can significantly influence nutrient cycling in coastal ecosystems. However, the impact of marine aquaculture on the dynamics of dissimilatory nitrate reduction processes (DNRPs) and the fate of reactive nitrogen remain poorly understood. In this study, the rates of DNRPs and the abundances of related functional genes were investigated in aquaculture and non-aquaculture areas. The results showed that marine aquaculture significantly increased the denitrification (DNF) and dissimilatory nitrate reduction to ammonium (DNRA) rates and decreased the rate of anaerobic ammonium oxidation (ANA), as compared with non-aquaculture sites. DNF was the dominant pathway contributing to the total nitrate reduction, and its contribution to the total nitrate reduction significantly increased from 66.72% at non-aquaculture sites to 78.50% at aquaculture sites. Marine aquaculture can significantly affect the physicochemical characteristics of sediment and the abundances of related functional genes, leading to variations in the nitrate reduction rates. Although nitrate removal rates increased in the marine aquaculture area, ammonification rates and the nitrogen retention index in the aquaculture areas were 2.19 and 1.24 times, respectively, higher than those at non-aquaculture sites. Net reactive nitrogen retention exceeded nitrogen removal in the aquaculture area, and the retained reactive nitrogen could diffuse with the tidal current to the entire bay, thereby aggravating N pollution in the entire study area. These results show that marine aquaculture is the dominant source of nitrogen pollution in semi-enclosed bays. This study can provide insights into nitrogen pollution control in semi-enclosed bays with well-developed marine aquaculture.

Haw-Ming Huang,1,2 Ping-Han Wu,3 Po-Chien Chou,4 Wen-Tien Hsiao,5 Hsin-Ta Wang,4 Hsin-Pei Chiang,3 Chi-Ming Lee,6 Shwu-Huey Wang,6 Yu-Cheng Hsiao2,7 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4School of Organic and Polymeric, National Taipei University of Technology, Taipei, Taiwan; 5Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan; 7Cell Physiology and Molecular Image Research Center, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Yu-Cheng Hsiao; Ping-Han WuTaipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, TaiwanTel +886-291-937-9783Fax +886 2 27362295Email ychsiao@tmu.edu.tw; gahwclbjwph@gmail.comIntroduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.Keywords: hyaluronic acid, Fe3O4 nanoparticles, TOF-SIMS, MRI

The new heterocyclic compound 4-methyl-3-((4-(pyridin-3-yl) pyrimidin-2-yl) amino) benzoic acid (1) designed utilizing methyl 3-amino-4-methylbenzoate (2) as a starting material was successfully fabricated and eventually characterized utilizing single crystal X-ray crystallography, 1H NMR and IR. In biological study, to evaluate the protective effect of compound on acute tracheobronchitis ICR mice model, the ELISA assay was performed to determine the level of inflammatory mediators IL-6 and TNF-α in serum. Then, the western blot was performed to determine the activation of PKA-NF-κB pathway in tissues.

We aimed to investigate the role of the quantitative parameters of dual-energy computed tomography (DECT) in evaluating patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We retrospectively identified 80 HCC patients (mean age, 56 years; 61 men) treated by TACE who received contrast-enhanced DECT and were retreated by TACE within 7 days between November 2018 and December 2019. Taking digital subtraction angiography (DSA) and CT images as reference standard, two readers measured and calculated the values of normalized iodine concentration at arterial phase (NICAP), normalized iodine concentration at portal venous phase (NICPP), iodine concentration difference (ICD), arterial iodine fraction (AIF) and slope of the spectral Hounsfield unit curve (λHu) by placing matched regions of interests (ROIs) within the tumor active area (TAA), adjacent normal hepatic parenchyma (ANHP) and tumor necrotic area (TNA). Differences between the parameters were analyzed by the Kruskal–Wallis H test. Receiver operating characteristic analysis of the parameters performance in differentiating the three tissues types was performed. AIF exhibited a good performance in distinguishing TAA (0.93 ± 0.31) and ANHP (0.18 ± 0.14), the areas under the receiver operating characteristic curve (AUC) was 0.989, while the λHu exhibited an excellent performance in distinguishing TAA (3.32 ± 1.24) and TNA (0.29 ± 0.27), with an AUC of 1.000. In conclusion, quantitative DECT can be effectively used to evaluate the tumor viability in HCC patients treated by TACE.

Denitrification and anaerobic ammonia oxidation (anammox) play key roles in nitrogen (N) loss, and nitrification can supply substrates of NO2– and NO3– for denitrification and anammox. Coupled nitrification-denitrification/anammox processes are thus crucial for N removal in coastal ecosystems. This study aims to examine the spatial-temporal variations of ambient, coupled, and uncoupled N removal rates in the coastal sediments off the north East China Sea, and to clarify the controlling factors and microbial mechanisms of coupled nitrification-denitrification/anammox. The rates of ambient, coupled, and uncoupled denitrification and anammox in coastal sediments off the north East China Sea were quantified using the continuous-flow experiments combined with 15N isotope pairing technique. The quantitative polymerase chain reaction method was used to determine the abundances of nitrifiers, denitrifiers, and anammox bacteria, with the functional genes of amoA and nirS, and 16S rRNA gene, respectively. Ambient denitrification rates varied between 0.43 and 7.39 μmol N m−2 h−1, and ambient anammox rates ranged from 0.05 to 0.62 μmol N m−2 h−1. Coupled nitrification-denitrification was the dominant N removal pathway. The rates and coupling of N removal processes with nitrification varied distinctly between nearshore and offshore sites, which were driven by diverse environmental factors. Redundancy analysis suggested that nitrate and sulfide were important factors controlling the coupled and uncoupled N removal rates, and nitrate was proved to be the key factor influencing the ratio between coupled and uncoupled N removal via an integrated analysis. Abundances of ammonia oxidizing bacteria (AOB) correlated significantly with coupled denitrification rates and abundances of denitrifiers, suggesting the importance of AOB in coupled nitrification-denitrification. This study investigated the ambient, coupled, and uncoupled denitrification and anammox rates in coastal sediments off the north East China Sea. Nitrate was proved to be the critical factor influencing the ratio between coupled and uncoupled N removal, and AOB may play important role in coupled nitrification-denitrification. These results emphasized that nitrification is crucial for N removal with important implications on N loss in coastal ecosystems.

A mixed oxide supported bimetallic catalyst Ni25.38Co18.21/MgO–0.75Al2O3 was readily prepared and found to be efficient in the hydrogenation of valeronitrile (VN) to amylamine (AA) under atmospheric pressure. Under the optimal conditions: H2 to VN molar ratio of 4:1, NH3 to VN molar ratio of 3:1, reaction temperature of 130 °C and residence time of 5 s, the conversion of VN reached 100% with a AA yield of 70.8%, and a diamylamine (DAA) yield of 25.9%. This catalyst was also active in the hydrogenation of other low carbon aliphatic nitriles to their corresponding primary amines. The characterization results revealed that the catalyst had the properties of large surface area, uniform and fine dispersion of metal particles in the form of Ni/Co alloy with synergy effect between the two metals, which endowed the catalyst with good catalytic performances in the hydrogenation reaction of aliphatic nitriles.

Asgard archaea are widely distributed in anaerobic environments. Previous studies revealed the potential capability of Asgard archaea to utilize various organic substrates including proteins, carbohydrates, fatty acids, amino acids and hydrocarbons, suggesting that Asgard archaea play an important role in sediment carbon cycling. Here, we describe a previously unrecognized archaeal phylum, Hermodarchaeota, affiliated with the Asgard superphylum. The genomes of these archaea were recovered from metagenomes generated from mangrove sediments, and were found to encode alkyl/benzyl-succinate synthases and their activating enzymes that are similar to those identified in alkane-degrading sulfate-reducing bacteria. Hermodarchaeota also encode enzymes potentially involved in alkyl-coenzyme A and benzoyl-coenzyme A oxidation, the Wood–Ljungdahl pathway and nitrate reduction. These results indicate that members of this phylum have the potential to strictly anaerobically degrade alkanes and aromatic compounds, coupling the reduction of nitrate. By screening Sequence Read Archive, additional genes encoding 16S rRNA and alkyl/benzyl-succinate synthases analogous to those in Hermodarchaeota were identified in metagenomic datasets from a wide range of marine and freshwater sediments. These findings suggest that Asgard archaea capable of degrading alkanes and aromatics via formation of alkyl/benzyl-substituted succinates are ubiquitous in sediments.

Many marine polysaccharides as prebiotics can promote host health by modulating gut microbiota. This study investigated the beneficial effects of purified marine plant-derived Gelidium pacificum Okamura polysaccharide (GPOP-1) and marine animal-derived Cereus sinensis polysaccharide (CSP-1) on normal mice by modulating gut microbiota. The composition and diversity of gut microbiota were evaluated using 16S rRNA high-throughput sequencing. The results showed that GPOP-1 and CSP-1 altered the composition of the gut microbiota and promoted the growth of beneficial bacteria. At the genus level, GPOP-1 increased the relative abundance of Bacteroides, Phascolarctobacterium, and decreased the relative abundance of Ruminococcus, Helicobacter, Allobaculum, Dorea and AF12. While CSP-1 increased the relative abundance of Coprococcus, Adlercreutzia, Roseburia, Phascolarctobacterium, and decreased the relative abundance of Bacteroides, Ruminococcus and Oscillospira. The changes in the gut microbiota may affect the body weight, immune organ index and the production of short-chain fatty acids in normal mice. Compared to the normal control group, GPOP-1 decreased average weight gain while CSP-1 increased average weight gain. Furthermore, both GPOP-1 and CSP-1 significantly increased thymus and spleen indexes and total short chain fatty acids production in mice. In summary, GPOP-1 and CSP-1 exerted prebiotic effects on normal mice.

Vitamin D deficiency is co-prevalent with various liver diseases including cirrhosis, while the underlying mechanism remains elusive. Vitamin D receptor (VDR) is abundantly expressed in the distal region of small intestine, where the Paneth cells are enriched, suggesting that vitamin D signaling may modulates the intestinal Paneth cells and their production of defensins to restrain microbiome growth in the small intestine. In this study we found that in carbon tetrachloride-induced liver injury, hepatic 25-hydroxylation of vitamin D was impaired, leading to down regulated expression of Paneth cell fensins in the small intestine, gut dysbiosis, and endotoxinemia. While intraperitoneal injection of endotoxin (lipopolysaccharides) alone did not elicit liver fibrosis, it exacerbated the carbon tetrachloride initiated liver fibrogenesis. Oral gavage of synthetic Paneth cell alpha-defensin 5 (DEFA5) restored the homeostasis of gut microbiota, reduced endotoxemia, relieved liver inflammation, and ameliorated liver fibrosis. Likewise, Cholestyramine, cationic resin that can sequestrate endotoxin in the intestine, attenuated the liver fibrosis as well. Fecal transplant of the microbes derived from the DEFA5-treated donors improved liver fibrosis in the recipient mice. The intestinal Vdrconditional knockout mice exhibited reduction of Paneth cell defensins and lysozyme production, and worsened liver injury and fibrogenesis. Thus, liver injury impairs synthesis of 25(OH)VD3, which consequently impedes the Paneth cells functions in the small intestine, leading to gut dysbiosis for liver fibrogenesis.

The aim of this study was to investigate the regulatory function of the non-coding microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in alcoholic hepatitis (AH) and its potential mechanism associated with the mitogen-activated protein kinase (MAPK) signaling pathway. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TBIL), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured in a rat model of AH. The biological prediction website microRNA.org and dual-luciferase reporter gene assay were used to identify whether SOCS1 was a direct target of miR-155, and the effects of miR-155 and SOCS1 on the viability, cycle progression, and apoptosis of hepatic stellate cells were assessed using RT-qPCR, Western blot assay, MTT assay, Annexin V/PI double staining, and PI single staining. The levels of ALT, AST, MDA, and TBIL and the liver cell morphology were all prominently changed in AH model rats. miR-155 suppressed SOCS1 by specifically binding to SOCS1-3’-UTR to activate the MAPK signaling pathway. SOCS1 had low expression while miR-155 was highly expressed in AH rats. miR-155 promoted hepatic stellate cell viability and cycle progression and reduced cell apoptosis by silencing SOCS1. Together, we find that silenced miR-155 could upregulate SOCS1 and inactivate the MAPK signaling pathway, thereby inhibiting the proliferation of alcoholic hepatic stellate cells and promoting cell apoptosis.

Direct sulfonamidation of quinoxalin-2(1H)-one derivatives has been developed using a readily available Cu salt as the catalyst and inexpensive ammonium persulfate as the oxidant in moderate conditions. Owing to the feature of handy operation and good functional group tolerance, this method provides a convenient and efficient access to curative 3-sulfonamidated quinoxalin-2(1H)-one scaffolds.

Chronic fructose consumption and vitamin D deficiency (VDD) diet have been linked to the pandemic of metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD). The metabolic mechanisms remain unclear. This study is to explore metabolic changes of mice fed with high fructose syrup and VDD diet in the biogenesis of MetS and NAFLD. C57BL/6J mice were treated with four conditions for 28 weeks: control (standard chow and sterile water), fructose drinking (FD, standard chow and 20 g/100 mL fructose in drinking water), VDD (standard chow with VD depleted and sterile water), and FD+VDD. Metabolites in the serum and liver of mice were analyzed by gas chromatography-mass spectrometry combined with trimethylsilyl derivatization. The histological results indicated that one-hit from long-term fructose drinking led to mild MetS, and a combination with VDD diet induced hepatic steatosis, inflammatory lesion, and interstitial fibrosis in mice, showing significant nonalcoholic steatohepatitis features. Metabolomics analysis showed significant changes in amino acids and short-chain organic acids in response to fructose drinking. VDD diet led to significant increase of hepatic fatty acids, which was consistent with the hepatic morphology of fat deposition. This work demonstrated a concert effect of FD and VDD in promoting MetS and NAFLD through changing in vivo metabolism and signaling pathways. And metabolomics analysis could provide early warnings for the biogenesis of MetS and NAFLD. Importantly, vitamin D supplementation in the diet can balance the metabolic disorders caused by excessive fructose intake.

Background Bladder cancer (BC) is a common malignancy worldwide that accounts for 3% of global cancer diagnoses. Chemotherapy resistance limits the therapeutic effect of chemotherapeutic agents in patients with BC. Prolyl 4-hydroxylase, beta polypeptide (P4HB) is an endoplasmic reticulum (ER) chaperone that is upregulated in bladder cancer tissues (The Cancer Genome Atlas, TCGA datasets). Knockdown or suppression of P4HB exerts anticancer activity and sensitizes cells to chemotherapy in various types of cancer. Purpose We aimed to investigate whether the inhibition of P4HB enhances the anticancer efficacy of gemcitabine (GEM) in BC cells and to study the underlying molecular mechanisms. Patients and Methods The P4HB mRNA expression levels of 411 BC patients from the TCGA database and P4HB expression level of eighty BC paraffin-embedded samples detected by immunohistochemistry (IHC) staining were used for clinical feature and prognostic analyses. Bioinformatics analysis was utilized for the mechanistic investigation. Highly P4HB-expressed BC cell lines (T24 and 5637) treated with P4HB inhibitor (Bacitracin, BAC) were used to study the effects of BAC on the sensitivity of BC cells to GEM and the potential mechanism. P4HB inhibition experiments were performed in highly P4HB-expressed BC cells, and cell viability, colony formation, cell cycle, reactive oxygen species (ROS), apoptosis and pathway proteins were assessed in T24 and 5637 cells. Results Western blot analysis showed that P4HB expression was significantly higher in BC tissues than in paired normal tissues. IHC showed that patients with high P4HB expression had a poorer overall survival (OS) rate than those with low P4HB expression. Furthermore, increased P4HB expression was demonstrated to be an independent prognostic marker for BC. Functionally, P4HB inhibition by BAC decreased the cell proliferation ability in vitro. Moreover, BAC treatment sensitized BC cells to GEM. Molecular mechanism analysis indicated that inhibition of P4HB by BAC treatment enhanced the anticancer effects of GEM through increasing cellular ROS content and promoting cell apoptosis and PERK/eIF2α/ATF4/CHOP signaling. Conclusion High P4HB expression was significantly correlated with poor prognosis in BC patients. Inhibition of P4HB by BAC decreased the cell proliferation ability and sensitized BC cells to GEM by activating apoptosis and the PERK/eIF2α/ATF4/CHOP pathways.

Development of efficient and robust electrode materials is significant for sodium-ion batteries (SIBs). Metallic selenides have been widely investigated as a promising anode material based on their relatively high theoretical capacity. However, rapid capacity fading and huge volume changes greatly hinder their practical application. Herein, for the first time, uniform yolk-shell Fe7Se8@C/N nanoboxes (Fe7Se8@C/N NBs) with the Fe7Se8 cores completely embedded by a thin and robust carbon shell are prepared using a strategy of facile etching method combined with selenization for advanced anode materials for SIBs. Benefiting from the unique structural merits, the Fe7Se8@C/N NBs electrodes for Na-ion half cells exhibit high Na-ion storage capacity (385.5 mAh g−1 at 0.1 A g−1) and superior rate performance (316.0 mAh g−1 at 5 A g−1) as well as impressive cyclability with no capacity decay over 1000 cycles. The sodium storage mechanism of Fe7Se8@C/N NBs electrode is systematically studied with the aid of ex-situ X-ray diffraction and transmission electron microscopy. Finally, the assembled full cells coupled with the lab-made high-voltage Na3V2(PO4)2O2F cathode and Fe7Se8@C/N NBs anode materials show superior energy-storage performance.

N-acyl-L-homoserine lactones (AHLs) based quorum sensing (QS) phenomenon is recognized as an effective agent for regulating bacterial growth and metabolism. However, diversity and biological role of AHLs in natural environments remain largely unknown. This study focuses on compositions of AHLs and their potential role in nitrogen transformation in intertidal marshes. We investigated the levels of AHLs in rhizosphere (Phragmites australis, Spartina alterniflora and Scirpus mariqueter) and non-rhizosphere soils from Chongming eastern intertidal wetland of the Yangtze Estuary using gas chromatography-mass spectrometry (GC/MS). Molecular techniques were employed to investigate the compositions and structure of bacterial community. Soil-slurry experiments in combination with nitrogen isotope tracing technique were conducted to examine the effects of AHLs on nitrogen transformation processes. AHLs were higher in rhizosphere than non-rhizosphere soils, and correlated significantly with soil organic carbon and pH. C6-, C8-, C10- and C12-HSLs were identified as the probably universal QS signal molecules in intertidal marsh soils. The bacterial biodiversity might be regulated by AHLs, and 12 of the 50 most abundant microorganisms in intertidal marsh soils were related significantly with AHL concentrations. Furthermore, C6-, C8- and C12-HSLs might play an important role in mediating nitrogen transformation processes including nitrification, denitrification and anaerobic ammonium oxidation (anammox). AHLs are favored to accumulate in rhizospheric environments and thus further mediate the bacterial diversity and soil nitrogen cycling. This study highlights the associations of QS signal molecules with the dynamics and activity of nitrogen cycling bacteria in intertidal marshes.

A novel Lewis acid-catalyzed, highly efficient, practical, and atom-economical protocol for the synthesis of functionalized 1,2-dihydropyridine-3-carbonitrile derivatives in the presence of Bi(OTf)3 (10 mol %) in tetrahydrofuran (2.0 mL) at 80 °C for 8 h in air is described, starting from readily accessed propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles. This cycloaddition protocol, which is scalable and proceeds under mild conditions, is amenable to the gram-scale construction of valuable 1,2-dihydropyridine-3-carbonitriles. Furthermore, the good functional group compatibility and broad scope of this strategy were demonstrated by a broad range of propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles, with yields ranging from 34 to 96%.

In this study, La(OH)3-modified magnetic sodium carboxymethyl cellulose (La-MC) was prepared as adsorbents for phosphate, which exhibited excellent adsorption performance up to 62.98 mg P/g and magnetic property for easy recovery. The recovered adsorbents after phosphate sorption were subsequently used for photocatalytic reduction of Cr(VI) and possessed good photocatalytic activity. This work provided an excellent reference for developing a new way of extending life cycle of adsorbents by combining phosphate adsorption with photocatalysis for sequential removal of pollutants from water in the future.

Faced with fossil fuel depletion and increasing environmental concerns, the conversion of renewable biomass into fuels or chemicals is promising but extremely challenging due to the inertness and complexity of biomass. Therefore, in situ multistage condensation combined with the HDO of pyrolysis bio-oil was chosen to reduce the complexity and improve the quality of bio-oil. In addition, the activity and stability of the catalyst was enhanced. The bio-oil obtained via continuous pyrolysis was divided into four-stage depending on their boiling point via in situ multistage condensation. After HDO, the relative content of long-chain alkanes was over 80% for each stage bio-oil via mixed supported Ni/HZSM-5-γ-Al2O3 catalyst. Especially, the main components in the 3rd oil (aqueous phase) were n-heneicosane (31.60%), icosane (5.13%) and n-heptadecane (4.36%) based on the highest HDO ratio. Moreover, the reaction mechanism was discussed via the HDO of model bio-oil. The main reaction pathway consisted of hydrogenation and dehydration reactions (HYD pathway), and a side reaction was the direct deoxygenation route (DDO pathway). This work provides a general and efficient pathway for directly converting biomass into valuable long chain alkanes.

Cystinuria is an inherited disease characterized by increased urinary cystine excretion and recurrent cystine stones. Current treatment regimens have limited effectiveness in preventing stone recurrence and are often poorly tolerated. The aim of this study was to evaluate the effect of tolvaptan, a vasopressin receptor 2 (V2) antagonist, on cystine stone volume in mice with cystinuria. Tolvaptan (0.4 mg per mouse) or placebo was delivered by gavage daily for 30 days. Urinary amino acids and cystine stones were analyzed to assess drug efficacy in preventing l-cystine stone growth using several analytical methods. Data were entered into SPSS and analyzed by paired sample T test. p value

Rationale: Emerging evidence suggests that noncentrosomal microtubules play an essential role in intracellular transport, cell polarity and cell motility. Whether these noncentrosomal microtubules exist or function in cancer cells remains unclear. Methods: The expression and prognostic values of CAMSAP2 and its functional targets were analyzed by immunohistochemistry in two independent HCC cohorts. Immunofluorescence and co-immunoprecipitation were used for detection of CAMSAP2-decorated noncentrosomal microtubule. Chromatin immunoprecipitation and luciferase report assays were used to determine the c-Jun binding sites in HDAC6 promoter region. In vitro migration and invasion assays and in vivo orthotopic metastatic models were utilized to investigate invasion and metastasis. Results: We reported a microtubule minus‑end‑targeting protein, CAMSAP2, is significantly upregulated in hepatocellular carcinoma (HCC) and correlated with poor prognosis. CAMSAP2 was specifically deposited on microtubule minus ends to serve as a “seed” for noncentrosomal microtubule outgrowth in HCC cells. Upon depletion of CAMSAP2, the noncentrosomal microtubule array was transformed into a completely radial centrosomal pattern, thereby impairing HCC cell migration and invasion. We further demonstrated that CAMSAP2 cooperates with EB1 to regulate microtubule dynamics and invasive cell migration via Trio/Rac1 signaling. Strikingly, both immunofluorescence staining and western blotting showed that CAMSAP2 depletion strongly reduced the abundance of acetylated microtubules in HCC cells. Our results revealed that HDAC6, a promising target for cancer therapy, was inversely downregulated in HCC and uniquely endowed with tumor-suppressive activity by regulation CAMSAP2-mediated microtubule acetylation. Mechanistically, CAMSAP2 activates c-Jun to induce transrepression of HDAC6 through Trio-dependent Rac1/JNK pathway. Furthermore, NSC23766, a Rac1-specific inhibitor significantly inhibited CAMSAP2-mediated HCC invasion and metastasis. Conclusions: CAMSAP2 is functionally, mechanistically, and clinically oncogenic in HCC. Targeting CAMSAP2-mediated noncentrosomal microtubule acetylation may provide new therapeutic strategies for HCC metastasis.

Biomimetic photocatalysis as an important organic transformation strategy has received increasing attention, with the performances of biomimetic catalysts largely depending on their design. This protocol has been initially used to fabricate a biomimetic photocatalyst of single-atom iron site through coupling carbon nitride with hemin (CNH) for the visible light-promoted sulfonation of alkenes to produce β-ketosulfones with up to 94% yield. The experimental results show that the role of CN in CNH is concentrated on enhancing the separation ability of photogenerated electron pairs and holes to improve the photocatalytic activity and stability. Moreover, the as-prepared photocatalyst of single atom iron can be irradiated under near-infrared light with a satisfactory yield, and is also feasible for the sulfonation reactions of androstenones. Importantly, this biomimetic catalysis-based synthesis system has some merits, namely high catalysis efficiency, favorable recyclability, high turnover number, and excellent functional group tolerance, making it promising for extensive applications in organic transformations for the synthesis of β-ketosulfones to access various bioactive drugs.

A silver-catalyzed formal [3 + 3] annulation of 3-methyleneisoindolin-1-one with alkynol for the synthesis of 1,5-dihydroindolizin-3(2H)-one derivatives is disclosed. The protocol allows practical synthesis of N-heterocyclic scaffolds with a broad scope of functional groups and could be efficiently scaled up to gram scale, which incarnates a potential application of this methodology. In addition, a range of chlorine anion substitution of alkenes can be constructed by adjusting the structure of the alkynol substrates with the use of TMSCl.

Raphidiopsis raciborskii (previously Cylindrospermopsis raciborskii) can produce cylindrospermopsin (CYN) which is of great concern due to its considerable toxicity to human and animals. Its CYN-producing (toxic) and non-CYN-producing (non-toxic) strains co-exist commonly in natural water bodies, while how their relative dominance is regulated has not been addressed. In this study, we combined field investigation with laboratory experiments to assessed the relationship between toxic and non-toxic R. raciborskii abundances under different nutrient levels. The rpoC1- and cyrJ-based qPCR was applied for quantifying total and toxic R. raciborskii abundances, respectively. The field survey showed that toxic R. raciborskii was detected in 97 of 115 reservoirs where its proportion ranged from 0.3% to 39.7% within the R. raciborskii population. Both total and toxic R. raciborskii abundances increased significantly with trophic level of these reservoirs, consistent with our monoculture and co-culture experiments showing in an increase in R. raciborskii growth with increasing nitrogen (N) or phosphorus (P) concentrations. In the monoculture experiments, growth rates of non-toxic and toxic strains from Australia or China were not significantly different under the same culture conditions. On the other hand, in the co-culture experiments, the toxic strains displayed a significantly faster growth than non-toxic strains under nutrient-replete conditions, resulting in an obvious shift toward the dominance by toxic strains from day 3 to the end of the experiments, regardless of the strain originating from Australia or China. The reverse was found under N- or P-limited conditions. Our results indicated that the toxic strains of R. raciborskii have a competitive advantage relative to the non-toxic strains in a more eutrophic world. In parallel to an increase in dominance, both toxic strains grown in the mixed population significantly increased CYN production under nutrient-replete conditions as compared to nutrient-limited conditions, suggesting that CYN may be of significance for ecological advantage of toxic R. raciborskii. These results highlight the importance of nutrient availability in regulating abundances and strain dominance of two genotypes of R. raciborskii. Our findings demonstrated that elevated nutrients would favor the growth of CYN-producing R. raciborskii and CYN production, leading to more blooms with higher toxicity at global scale.

Previously it was found that hsa_circ_105039 was underexpressed in the heart tissue of patients with congenital heart disease (CHD). However, the function and mechanism of hsa_circ_105039 in CHD are unclear. In the present study, induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes using 1% dimethyl sulfoxide (DMSO). Cell differentiation, viability, migration and apoptosis were measured before and following hsa_circ_105039 knockdown or overexpression. The results indicated that hsa_circ_105039 overexpression promoted cell differentiation, viability and migration; whereas apoptosis was simultaneously repressed. A luciferase reporter assay verified that hsa_circ_105039 acted as a sponge for microRNA (miR)-17 and that cyclinD2 was a direct target of miR-17. Furthermore, differentiation-related genes and proteins were analyzed by reverse transcription-quantitative PCR and western blotting, respectively. The results showed that hsa_circ_105039 could also upregulate the expression of differentiation-related genes and proteins, including natriuretic peptide A, cardiac troponin I, GATA-binding protein 4 and homobox transcription factor, in iPS cells. The results suggested that hsa_circ_105039 exerted a protective effect by promoting miR-17/cyclinD2 in DMSO-induced iPS cardiomyocytes, which indicated that hsa_circ_105039 is a potential key molecule for the diagnosis of CHD.

Potentially toxic Cylindrospermopsis raciborskii blooms are of emerging concerns, as its scale is spreading from tropical regions to high latitudes, increasing the risk of aquatic biota being exposed to cylindrospermopsin (CYN). So far, CYN-producing C. raciborskii strains have only been reported in tropical waters which are commonly phosphorus (P)-deficient, where they can dominate phytoplankton communities. However, the influence of CYN on phytoplankton communities under different P status remains unclear. In this study, we first analyzed the summer observations of 120 tropical reservoirs in Guangdong Province. The proportion of potential CYN-producers was significantly higher in P-deficient and CYN-present reservoirs than that in P-sufficient or CYN-absent ones. This suggested that in P-deficient condition, the potential CYN producers might gain more advantages by the help of CYN. Then, in laboratory experiments we found that upon P deprivation, CYN did not inhibit the cell growth of other algal cells, but significantly stimulates them to secret more alkaline phosphatase (ALP) than in P-sufficient condition. Through transcriptomics, we further revealed that under such P-deficient condition, CYN remarkably induced intracellular nitrogen allocation and protein export system by activating the PIK3/Akt-cGMP/PKG signaling pathways in Scenedesmus bijugatus, thus enhancing its ALP secretion. Our study implies that CYN-induced ALP secretion is facilitated upon P deficiency, thus supporting the dominance of its producers C. raciborskii.

A new polyketide-derived metabolite, named neglectine A, was isolated from cultures of the endophytic fungus Pestalotiopsis neglecta. Its structure was elucidated by analysis of 1D and 2D spectroscopic data as well as MS. Neglectine A possessed a rare bis-tetrahydrofuran ring system and showed moderate activities against SHP1, CDC25B, and PTP1B, with IC50 value of 17.1 μg/mL, 24.0 μg/mL, and 6.7 μg/mL, respectively. It is important to note that neglectine A has exhibited significant selectivity between PTP1B and CDC25B, LAR, SHP1, and SHP2. This is the first time that neglectine A is reported to have significant PTP1B inhibitory action.

In this paper, a new magnetic polymer-supported phosphate adsorbent MPVC-EDA-Ce was prepared by loading cerium (hydr)oxides onto ethylenediamine-functionalized polyvinyl chloride for the first time. MPVC-EDA-Ce showed excellent adsorption performances towards phosphate and easy recovery. The adsorption isotherm and kinetics of MPVC-EDA-Ce followed Langmuir monolayer model and the pseudo-second-order model, respectively. The pH results demonstrated that the MPVC-EDA-Ce could effectively remove phosphate in a wide range of pH with insignificant cerium leaching. Furthermore, analyses on adsorption mechanism and effect of competing anions demonstrated the formation of strong inner-sphere complexation between cerium (hydr)oxides and phosphate, which was a selective adsorption process, while positively charged quaternary ammonium groups adsorbed phosphate via relatively weak electrostatic attraction which was a non-selective adsorption process. The study provided a good reference to design novel phosphate adsorbents with two even more functional adsorption sites and a deep insight to investigate the adsorption mechanism towards phosphate.

Bismuth oxyiodide (BiOI) with 3D microspheres structure was prepared and used for adsorption of phosphate and photodegradation of dyes in phosphate-dye binary system for the first time. BiOI exhibited excellent adsorption capacity of phosphate up to 55.80 mg P/L and outstanding photocatalytic activities for all the cationic dyes in phosphate-cationic dye binary system. RhB was 100% photodegraded within 50 min, and the photodegradation rates of MB and FB reached 92% and 95% within 100 min, respectively. But in phosphate-anionic/neutral dye binary system, BiOI displayed only good adsorption performance of phosphate but showed no photodegradation performance for anionic or neutral dyes. The mechanism was proposed as that PO43− adsorbed on the surface of BiOI, which changed from being neutral into being negatively charged, and then the cationic dyes were absorbed due to electrostatic attraction for photodegradation. The photodegradation was confirmed that the photogenerated electrons from the conduction band (CB) of BiOI which could reduce O2 to ·O2− and associate with h+ oxidized the cationic dyes. This work established a new approach of photodegrading organic dyes and adsorbing phosphate in waterbodies, and provided a new insight into wastewater treatment with two or more pollutants.

In this study, we propose a novel strategy, plasma activated water (PAW) to reduce pesticide residues on agricultural products. To validate its feasibility and effectiveness, we employee high-performance liquid chromatography (HPLC) to detect phoxim on grapes. HPLC results suggest that the reduction of phoxim on grapes achieve 73.60% after treated 10 min by PAW prepared 30 min, and the concentration of phoxim decreased significantly (p 0.05) with the preparation time of PAW. Furthermore, HPLC-MS analysis shows that the reduction effect of phoxim by PAW is dominated by the degradation of phoxim. Combined with analyzing the physicochemical properties of PAW, one possible degradation pathway is proposed under the present experimental conditions, mediated by reactive oxygen and nitrogen species. The acidic environment (pH 3) and high oxidation capacity (ORP 500 mV) are suggested to be a benefit to the reduction of phoxim. Besides, the experimental results regarding color, firmness, sugar, vitamin C, and superoxide dismutase of grapes demonstrate that the PAW treatment will not significantly affect the quality of grapes. In conclusion, phoxim pesticide residues on grapes could be effectively reduced by the PAW strategy and without a significant (p 0.05) effect on grapes quality.

Cylindrospermopsin (CYN) is of great concern to human and animal health due to its potential toxicity. The cyanobacterium Cylindrospermopsis raciborskii is considered the most common cyanobacterial species that produces CYN. The discovery of the cyr gene cluster responsible for CYN biosynthesis allows us to develop molecular methods that detect and quantify potentially CYN-producing C. raciborskii. This paper describes the development of real-time PCR (qPCR) assays capable of quantifying the total and CYN-producing C. raciborskii in subtropical reservoirs of southern China. We designed primers and probes specifically targeting the rpoC1 and cyrJ genes of C. raciborskii, and enabling quantification of its total cell numbers and potentially toxic genotypes, respectively. The qPCR showed strong linearity between 102 and 106 copies per reaction for both genes. This molecular method was validated against microscopic counting and a high correlation was found between them for quantifying C. raciborskii cell numbers in cyanobacterial cultures and water samples. Using qPCR, we detected potentially CYN-producing C. raciborskii in 34 of the 46 subtropical reservoirs of southern China, with the cyrJ/rpoC1 proportion ranging from 0.3 to 34.7%. CYN concentrations significantly correlated with both the copy numbers of cyrJ gene and the proportion of toxic C. raciborskii. Thus, the present real-time PCR method provides a reliable and faster method for estimating the potential toxicity of C. raciborskii blooms in this region. The wide distribution of potential CYN-producing C. raciborskii in the investigated subtropical reservoirs highlights the need for further monitoring.

The abilities of three phylogenetically distant ammonia oxidizers, Nitrososphaera gargensis, an ammonia-oxidizing archaeon (AOA); Nitrosomomas nitrosa Nm90, an ammonia-oxidizing bacterium (AOB); and Nitrospira inopinata, the only complete ammonia oxidizer (comammox) available as a pure culture, to biotransform seven sulfonamides (SAs) were investigated. The removals and protein-normalized biotransformation rate constants indicated that the AOA strain N. gargensis exhibited the highest SA biotransformation rates, followed by N. inopinata and N. nitrosa Nm90. The transformation products (TPs) of sulfadiazine (SDZ), sulfamethazine (SMZ) and sulfamethoxazole (SMX) and the biotransformation mechanisms were evaluated. Based on the analysis of the TP formulas and approximate structures, it was found that during biotransformation, i) the AOA strain carried out SA deamination, hydroxylation, and nitration; ii) the AOB strain mainly performed SA deamination; and iii) the comammox isolate participated only in deamination reactions. It is proposed that deamination was catalyzed by deaminases while hydroxylation and nitration were mediated by nonspecific activities of the ammonia monooxygenase (AMO). Additionally, it was demonstrated that among the three ammonia oxidizers, only AOB contributed to the formation of pterin-SA conjugates. The biotransformation of SDZ, SMZ and SMX occurred only when ammonia oxidation was active, suggesting a cometabolic transformation mechanism. Interestingly, SAs could also be transformed by hydroxylamine, an intermediate of ammonia oxidation, suggesting that in addition to enzymatic conversions, a microbially induced abiotic mechanism contributes to SA transformation during ammonia oxidation. Overall, using experiments with pure cultures, this study provides important insights into the roles played by ammonia oxidizers in SA biotransformation.

Objectives Microbiota dysbiosis in inflammatory bowel disease (IBD) has been widely reported. The gut microbiota connect diet to the metabolism by producing small molecules via diverse metabolic pathways. In this study we aimed to investigate the dietary preferences of IBD patients, and to explore the interactions among gut microbiota composition, dietary components, and metabolites in relation to IBD. Methods Dietary preferences of IBD patients (including those with ulcerative colitis [UC] and Crohn's disease [CD]) and health controls were investigated, and their gut microbiota were analyzed using 16S rRNA gene sequencing and metagenomic analyses of fecal and biopsy samples. The metabolite profiles of the samples were then analyzed using gas and liquid chromatography-mass spectrometry analyses. Results The daily intake of folic acid, niacin, vitamins C and D, calcium, and selenium differed significantly between patients with IBD and healthy controls. A decrease in long-chain (such as arachidic, and oleic acid) and medium-chain fatty acids (sebacic acid and isocaproic acid) as well as bile acid was observed in patients with IBD. Compared with healthy controls, 22 microbial species (including Sulfolobus acidocaldarius, and Clostridium clostridioforme CAG132) in the UC group and 37 microbial species (such as Bacteroides fragilis and Fusobacterium nucleatum) in the CD group were found to be correlated to diet and metabolites. Bacteroides fragilis was enriched in patients with IBD and associated with multi-nutrients, and 21 metabolites including 25-hydroxyvitamin D3 and taurolithocholic acid. Conclusions This study provides an interaction network to identify key micronutrients, microbiota components and metabolites that contribute to IBD.

A plasma electrolytic oxidation (PEO) coating was fabricated on AA1060 alloy in an alkaline sodium hexametaphosphate ((NaPO3)6) electrolyte. The growth characteristic of the PEO coating was investigated by means of a substrate-detachment technique, Scanning electron microscope (SEM) equipped with energy dispersive spectrometry (EDS), X-ray photoelectron spectrometer (XPS), X-ray diffractometer (XRD) and Mott-Schottky analysis. The results showed that an ordered and porous anodic aluminum oxide (AAO) film was formed at the anodic oxidation stage by the influence of (NaPO3)6 in the electrolyte, and the microstructure of the AAO film induced the plasma discharge events to initiate inside the AAO film. The Mott-Schottky analysis showed that the PEO coated samples were all represented n-type semiconducting behavior. The microstructures of detached coatings showed that the coating/substrate interfaces formed at the anodic oxidation stage and sparking stage consist of numerous hemispherical cap structures, but with different sizes. It was also revealed that the inward growth of the hemispherical cap structures is dependent on the diffusion of oxygen from the electrolyte or plasma gases to substrate, and P atoms mainly exist in the amorphous phase of the PEO coating.

Plasma electrolytic oxidation (PEO) coatings were prepared on AA1060 alloy substrate by a galvanostatic regime in an alkaline sodium hexametaphosphate ((NaPO3)6) electrolyte, and the influences of ...

Spermatogonial stem cells (SSCs) self-renew and contribute genetic information to the next generation. Pig is wildly used as a model animal for understanding reproduction mechanisms of human being. Inducing directional differentiation of porcine SSCs may be an important strategy in exploring the mechanisms of spermatogenesis and developing better treatment methods for male infertility. Here, we established an in-vitro culture model for porcine small seminiferous tubule segments, to induce SSCs to differentiate into single-tail haploid spermatozoa. The culture model subsequently enabled spermatozoa to express the sperm-specific protein acrosin and oocytes to develop to blastocyst stage after round spermatid injection. The addition of retinoic acid (RA) to the differentiation media promoted the efficiency of haploid differentiation. RT-PCR analysis indicated that RA stimulated the expression of Stra8 but reduced the expression of NANOS2 in spermatogonia. Genes involved in post-meiotic development, transition protein 1 (Tnp1) and protamine 1 (Prm1) were upregulated in the presence of RA. The addition of an RA receptor (RAR) inhibitor, BMS439, showed that RA enhanced the expression of cAMP responsive-element binding protein through RAR and promoted the formation of round spermatids. We established an efficient culture system for in-vitro differentiation of pig SSCs. Our study represents a model for human testis disease and toxicology screening. Molecular regulators of SSC differentiation revealed in this study might provide a therapeutic strategy for male infertility.