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A series of pyrrolo[3,2‐f]quinoxaline derivatives have been obtained by a three‐component domino reaction of quinoxalin‐6‐amine, arylglyoxal monohydrates, and cyclic 1,3‐dicarbonyl compounds in ethanol medium at 80°C catalyzed by acetic acid. The notable features of this synthesis are excellent regioselectivity, operational simplicity, relatively mild reaction conditions, and good yields. [ABSTRACT FROM AUTHOR]

Herein, the microwave transmission method is proposed that demonstrates such advantages as non-invasiveness, excellent penetration performance, and fast detection. As a key component of the microwave method water content measurement instrument, the antenna is required to have a smaller radiation size than the inner diameter of the oil pipe. To address this technical challenge, a small-sized microwave projection method based on water content measurement antenna is designed in this study for the water content measurement of oil-water mixtures in downhole pipelines. Also, the half-cut antenna with a size of 17 × 45 m m 2 is proposed to operate in the frequency band of 2–6 GHz (The measured gain of the antenna varies from 2.48 dBi to 4.98 dBi). Then, the designed half-cut antenna is applied to the established water-content test environment for analysis as to the relationship between water content and the variation in transmission coefficient of the half-cut antenna. According to the test results, the relative water content error is about 0.31% between the simulation and measured results for the transmission coefficient S 21 in the range of 0%–30%, while that is about 0.16% for the transmission coefficient S 21 in the range of 40%–100%. The experimental results can be extended to the measurement of the part with high water content of the oil-water mixture in the pipeline, which provides a practical reference for field tests and basic research. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis–trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P < 0.001; IDC vs Normal: P = 0.007/P = 0.003; DCIS vs. FCC: P = 0.008/P = 0.004; IDC vs. FCC: P = 0.04/P = 0.043). The expression levels of TPL2 and Pin1 were positively correlated in DCIS and IDC groups (P = 0.001, P = 0.011). In the IDC group, the Ki67 level in the TPL2 overexpression group was significantly lower than that in the TPL2 low expression group (P = 0.02). The TPL2 overexpression rate was significantly higher in IDC with histological grades 1–2 than that in IDC with histological grade 3 (P = 0.029). The TPL2 overexpression rate in IDC with tumor-node-metastasis (TNM) stage I was significantly higher than that in IDC with TNM stages II–III (P = 0.035). We conclude that TPL2 and Pin1 may synergistically promote the occurrence and development of IDC, but TPL2 overexpression may be an early molecular event in IDC development. TPL2 overexpression is significantly related with IDC with lower malignancy or earlier TNM stage, suggesting that the prognosis of IDC patients with TPL2 overexpression may be better and TPL2 overexpression may be a predictor of good prognosis in IDC. [ABSTRACT FROM AUTHOR]

This study aims to investigate the regulation effects of Xuanhuang Runtong tablets (XHRTs) on intestinal microbes and inflammatory signal toll receptor 5 (TLR5)/interleukin-17A (IL-17A) in STC mice. First, high-performance liquid chromatography (HPLC) was used to verify the composition of XHRT and quality control. Then, the defecation ability of STC mice was evaluated by measuring fecal water content and intestinal transit function. The pathological examination of colonic mucosa was observed by Alcian Blue and periodic acid Schiff (AB-PAS) staining. 16S ribosomal DNA (16S rDNA) genes were sequenced to detect the fecal microbiota. Western blotting, immunofluorescence, and real-time fluorescence quantitative PCR (qRT-PCR) were applied to detect the expression of aquaporin 3 (AQP3), connexin 43 (Cx43), TLR5, and IL-17A. The defecation function of the STC mice was significantly decreased. The amount of mucus secretion and the thickness of the colonic mucus layer were decreased, and the number of microbial species in the intestinal wall, such as Firmicutes/Bacteroidetes, anaerobic bacteria, and Alistipes, were also decreased. In addition, the expression of AQP3 and Cx43 was disordered, and the inflammatory factorsTLR5 and IL-17A were activated in the colon. The changes in the above indicators were significantly reversed by XHRT. This study demonstrates that XHRT provides a new strategy for the treatment of slow transit constipation by regulating the activation of the intestinal inflammatory signal TLR5/IL-17A mediated by gut microbes. [ABSTRACT FROM AUTHOR]

NHC-catalyzed radical cross-coupling reactions have been recently developed; they provide an efficient method to access ketones from aldehydes or carboxylic acid derivatives with sp3-hybridized carbon radical precursors. This reaction has indirectly solved the limitations in the scope of coupling partners in NHC umpolung catalyzed reactions of aldehydes. In this short review, we present some recent advances in NHC-catalyzed radical reactions, with a focus on the construction of the C–C(CO) bond. 1 Introduction 2 Oxidative Generation of NHC-Derived Ketyl Radical 2.1 NHPI Redox-Active Esters 2.2 Katritzky Pyridinium Salts 2.3 Alkyl Halides 2.4 Aryl Halides 2.5 Compounds Containing N–O Bond 2.6 Diazo Esters 2.7 Others 3 Reductive Generation of NHC-Derived Ketyl Radical 3.1 Hantzsch Esters 3.2 Sulfinates 3.3 Electron-Rich Arenes 3.4 Amines 3.5 Organoborane Reagents 4 Conclusion [ABSTRACT FROM AUTHOR]

The INO80 chromatin remodeling complex plays an essential role in the regulation of gene transcription, which participate in a variety of important biological processes in cells including DNA repair and DNA replication. Difference from the yeast INO80 complex, metazoan INO80 complex have the specific subunit G, which is known as nuclear factor related to kappaB binding protein (NFRKB). Recently, NFRKB has been received much attention in many aspects, such as DNA repair, cell pluripotency, telomere protection, and protein activity regulation. To dig the new function of metazoan INO80 complex, a better understanding of the role of NFRKB is required. In this review, we provide an overview of the structure and function of NFRKB and discuss its potential role in cancer treatment and telomere regulation. Overall, this review provides an important reference for further research of the INO80 complex and NFRKB. [ABSTRACT FROM AUTHOR]

The bark and leaves of the Eucommia ulmoides Oliv. (E. ulmoides) have good medicinal value. Studies show endophytes play important roles in host medicinal plant secondary metabolite synthesis, with season being a key influencing factor. Therefore, we used 16 S rRNA to detect endophytic bacteria (EB) in E. ulmoides bark and leaves collected in winter, spring, summer, and autumn, and analyzed the contents of major active components respectively. The results showed that the species diversity and richness of EB of the E. ulmoides bark were higher than those of leaves in all seasons except fall. Among them, the higher species diversity and richness were found in the E. ulmoides bark in winter and spring. EB community structure differed significantly between medicinal tissues and seasons. Concurrently, the bark and leaves of E. ulmoides showed abundant characteristic EB across seasons. For active components, geniposidic acid showed a significant positive correlation with EB diversity and richness, while the opposite was true for aucubin. Additionally, some dominant EB exhibited close correlations with the accumulation of active components. Delftia , enriched in autumn, correlated significantly positively with aucubin. Notably, the impact of the same EB genera on active components differed across medicinal tissues. For example, Sphingomonas , enriched in summer, correlated significantly positively with pinoresinol diglucoside (PDG) in the bark, but with aucubin in the leaves. In summary, EB of E. ulmoides was demonstrated high seasonal dynamics and tissue specificity, with seasonal characteristic EB like Delftia and Sphingomonas correlating with the accumulation of active components in medicinal tissues. [ABSTRACT FROM AUTHOR]

As an advanced warning system, resource buffer can notify the use of resources and provide added protection to critical chain activities. However, most of the existing studies in the literature focus on locating actual time buffers at various locations. In this study, we locate bottleneck resource buffers along the critical chain and determines optimal time windows for the first time. Drawing on the theory of constraints, we take into account factors such as bottleneck resource sensitivity, the idle cost, the start time flexibility and the work flow on the critical chain, and develop a quantitative model for the optimal time window determination of resource buffer. The proposed method is tested and compared with the currently widely adopted buffer management method. Results of the computational experiment of the proposed method demonstrates its relative dominance over the predominant buffer management approach in terms of overall completion time, project cost, the probability of delay and the average buffer consumption ratio. [ABSTRACT FROM AUTHOR]

A strong link exists between iron oxides and soil organic carbon (SOC). However, the role of iron oxides in the preservation of SOC in agricultural soil remains poorly understood. In this study, we comprehensively examined the concentration, molecular composition and biological sources of iron oxide‐bound organic carbon (Fe‐bound OC) in arable soils collected from 12 sites in central and east China. The results indicated that 6.2–31.2% of the SOC was bound to iron oxides in agricultural soil and that the binding mechanisms varied from adsorption in most soils to coprecipitation in those with a large content of organic carbon. The distribution of Fe‐bound OC showed no clear variation in relation to site, but Fe‐bound OC reached a peak in soils with an annual mean temperature of 16.4°C. Correlation analysis demonstrated that TOC might be the main determinant for the amount of Fe‐bound OC and that the binding mechanism is influenced by both TOC and the active Fe ratio. Comprehensive studies of C/N, 13C isotope and synchrotron radiation‐based Fourier transform infrared (SR‐FTIR) spectroscopy showed that iron oxides selectively protected plant‐derived aliphatic compounds and polysaccharides in agricultural soil. This study revealed the quantitative characterization, biological sources and molecular composition of Fe‐bound OC in arable soils, which provides useful information for evaluating and managing the global C cycle under the framework of climate change. Highlights: The binding of organic carbon by iron oxides in arable soils was measured.Approximately 6.2–31.2% of the soil organic carbon is associated to iron oxides (Fe‐bound OC).The distribution of Fe‐bound OC showed no clear variations in relation to sites.Iron oxides selectively stabilize plant‐derived polysaccharides and aliphatic compounds. [ABSTRACT FROM AUTHOR]

It is critical to understand the characteristics of public transportation networks (PTNs). Existing studies have mainly focused on the topological structure of PTNs and have revealed the commonalities of the topological structures of PTNs. However, few studies have examined the differences regarding topological structure characteristics between the PTNs of different cities. In addition, the nature and extent of the influence of specific urban geographic conditions and morphology on PTNs are unclear. This paper focuses on the influence of urban spatial and geographic environments on bus transportation networks (BTNs) by comparatively studying the topological and spatial attributes of two typical BTNs, respectively, from a mountainous city and a plain city in China, from the perspectives of basic statistical properties, types, connection properties, and spatial attributes, by using the complex networks theory and spatial analysis method. The results reveal that the two BTNs have similar statistical properties and they both have scale-free features as well as small-world features. However, these two BTNs are significantly different in the connection properties and spatial attributes. The difference is found closely related to the city’s geographic conditions and spatial morphology. The implications of this study regarding urban traffic planning and land planning are discussed. [ABSTRACT FROM AUTHOR]

The aim of the study is to determine the effects of iron on circadian clock gene expression and serum lipid metabolism in sucking piglets. Twenty-four neonatal piglets were selected and randomly assigned into three groups (A, B, and C) with eight replicates. Group A were received 1 mL physiological saline by intramuscular administration at d 3 and d 10; group B were received 1 mL iron dextran (100 mg) by intramuscular administration at d 3 and 1 mL physiological saline at d 10, respectively; group C were received 1 mL of iron dextran (100 mg) by intramuscular administration at both d 3 and d 10. Our results reveal that the relative expressions of Cry1, Cry2, Per1, Per2, and Bmal in liver were significantly different in the three groups (p < 0.05). Meanwhile, the content of triglyceride (TG) and high-density lipoprotein (HDL) in serum were also affected by the iron supplementation (p < 0.05). These results indicated that iron affected hepatic circadian clock genes significantly, meanwhile, it may possible association with lipid metabolism. [ABSTRACT FROM AUTHOR]

Background/Aims: Early weaning often causes gut dysfunction. Since serine alleviates oxidative stress and inflammatory response which are accompany with early weaning, we conducted the study to explore whether serine improves intestinal function in early-weaned piglets. Methods: Twenty-eight weaned piglets (aged 21 d) were fed either a basal diet or a basal diet plus 0.2% serine. We determined the effects of dietary serine supplementation on intestinal morphology by hematoxylin and eosin staining, expression of tight junction proteins (TJPs) by immunoblotting and immunofluorescence, expression of inflammatory cytokines and apoptosis markers by RT-qPCR and the level of antioxidant enzymes with ELISA kits in early-weaned piglets. Results: Serine supplementation increased daily body weight gain while decreasing diarrhea incidence. Both the jejunum and ileum of serine-supplemented piglets showed regularly arranged villi and microvilli. Moreover, dietary serine increased TJP expression, and alleviated apoptosis, inflammation, and oxidative stress in the intestine of early-weaned piglets. Conclusion: Our findings suggest that serine has the potential for use as a feed additive to prevent gut dysfunction caused by weaning. [ABSTRACT FROM AUTHOR]

An iridium (III) complex [Ir(ppy) 2 (BDPIP)]PF 6 ( Ir-1 ) was reported to show high anticancer activity and may be used as a potent anticancer drug. In the current study, we designed and synthesized a novel iridium (III) complex and evaluated its potential inhibitory effect on the cancer cell growth in vitro and in vivo. This complex was found to display high cytotoxic activity in vitro and in vivo against A549 cell with a low IC 50 value of 3.6 ± 0.3 μM and inhibiting percentage of tumor growth is 63.84% compared with the control. The complex also exhibited potencies superior to that of cisplatin toward A549 cell in vitro and in vivo. Further studies revealed that the complex can induce apoptosis and autophagy, enhance the ROS level, cause a decrease in the mitochondrial membrane potential and inhibit the cell invasion. Our findings indicated that the complex induced apoptosis in A549 through mitochondria dysfunction and PI3K/AKT/mTOR signaling pathways. [ABSTRACT FROM AUTHOR]

A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2- a :2′,3′- c ]phenazine) and its iridium(III) complex [Ir(ppy) 2 (THPDP)]PF 6 ( Ir-1 ) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1 H NMR and 13 C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC 50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0.03 and 1.6 ± 0.06 μM, respectively. The apoptosis was investigated with AO/EB and DAPI staining methods. The complex shows strong ability to inhibit the cell growth in B16, A549 and Eca-109 cells. Ir-1 can induce apoptosis, increase the intracellular ROS level, and cause a decrease in the mitochondrial membrane potential. The intracellular Ca 2+ level and the release of cytochrome c were studied under a fluorescent microscope. The cell invasion and autophagy were also performed, and the cell cycle arrest was assayed by flow cytometry. The expression of Bcl-2 family proteins, PI3K, AKT, mTOR, P-mTOR was investigated by western blot. The results show that the complex induces apoptosis through ROS-mediated mitochondria dysfunction and inhibition of AKT/mTOR pathways. These findings are helpful for design and synthesis of iridium(III) complexes as potent anticancer drugs. [ABSTRACT FROM AUTHOR]

A new ligand MHPIP (MHPIP = 2-(1-methyl-1 H -pyrazol-4-yl)-1 H -imidazo[4,5- f ][1,10]phenanthroline) and its three ruthenium (II) complexes [Ru(N-N) 2 (MHPIP)](ClO 4 ) 2 (N-N = phen: 1,10-phenanthroline 1 ; dmp = 2,9-dimethyl-1,10-phenanthroline 2 ; ttbpy = 4,4′-ditertiarybutyl-2,2′-bipyridine 3 ) were synthesized and characterized. The cytotoxic activity in vitro was studied by MTT method. The complexes 1 – 3 show moderate cytotoxic effects on the cell growth in HepG2 cells with an IC 50 value of 25.5 ± 3.5, 35.6 ± 1.9 and 27.4 ± 2.3 μM, respectively. The apoptosis was investigated with AO/EB and Annex V/PI staining methods and comet assay. The reactive oxygen species, mitochondrial membrane potential were investigated under a fluorescent microscope. Autophagy assay shows that the complexes can cause autophagy and up-regulate the expression of Beclin-1 protein. Additionally, the complexes inhibit the cell growth in HepG2 cells at G0/G1 phase, and the complexes can regulate the expression of caspase 3 and Bcl-2 family proteins. The studies demonstrate that the complexes induce apoptosis in HepG2 cells through DNA damage and ROS-mediated mitochondrial dysfunction pathways. [ABSTRACT FROM AUTHOR]

Diurnal variations in serum iron levels have been well documented in clinical studies, and serum iron is an important diagnostic index for iron-deficiency anemia. However, the underlying mechanism of dynamic iron regulation in response to the circadian rhythm is still unclear. In this study, we investigated daily variations in iron status in the plasma and liver of pigs. The transcripts encoding key factors involved in iron uptake and homeostasis were evaluated. The results showed that iron levels in the plasma and liver exhibited diurnal rhythms. Diurnal variations were also observed in transcript levels of divalent metal transporter 1 ( DMT1 ), membrane-associated ferric reductase 1 ( DCYTB ), and transferrin receptor ( TfR ) in the duodenum and jejunum, as well as hepcidin ( HAMP ) and TfR in the liver. Moreover, the results showed a network in which diurnal variations in systemic iron levels were tightly regulated by hepcidin and Tf/TfR via DCYTB and DMT1 . These findings provide new insights into circadian iron homeostasis regulation. The diurnal variations in serum iron levels may also have pathophysiological implications for clinical diagnostics related to iron deficiency anemia in pigs. [ABSTRACT FROM AUTHOR]

Two new ligand PTTP (2-phenoxy-1,4,8,9-tetraazatriphenylene) and FTTP (2-(3-fluoronaphthalen-2-yloxy)-1,4,8,9-tetraazatriphenylene) and their six ruthenium(II) polypyridyl complexes [Ru(N-N) 2 (PTTP)](ClO 4 ) 2 and [Ru(N-N) 2 (FTTP)](ClO 4 ) 2 (N-N = dmb: 4,4′-dimethyl-2,2′-bipiridine; dmp: 2,9-dimethyl-1,10-phenanthroline; ttbpy: 4,4′-ditertiarybutyl-2,2′-bipyridine) were synthesized and characterized. The cytotoxic activity of the complexes against cancer cells HeLa, BEL-7402, A549, HepG-2, HOS and normal cell LO2 was evaluated by MTT method. The IC 50 values range from 1.5 ± 0.1 to 55.9 ± 7.5 μM. Complex 3 shows the highest cytotoxic activity toward BEL-7402 cells (IC 50 = 1.5 ± 0.1 μM). Complex 5 displays most effective inhibition of the cell growth in A549 and HOS cells with low IC 50 values of 2.5 ± 0.6 and 2.6 ± 0.1 μM, respectively. The apoptosis, reactive oxygen species, mitochondrial membrane potential, DNA damage, autophagy and anti-metastasis assay were investigated under a fluorescent microscope. The cell cycle arrest was assayed by flow cytometry, and the expression of caspases and Bcl-2 family proteins was studied by western blot. The results obtained show that the complexes induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]

A new ligand PFPIP (PFPIP = 2-(2,3,4,5,6-pentafluorophenyl)[4,5- f ]imadazo [1,10]phenanthroline) and its four ruthenium(II) polypyridyl complexes [Ru(N N) 2 (PFPIP)](ClO 4 ) 2 (N N = dmb: 4,4′-dimethyl-2,2′-bipyridine, 1 ; bpy: 2,2′-bipyridine, 2 ; phen: 1,10-phenanthroline, 3 ; dmp: 2,9-dimethyl-1,10-phenanthroline, 4 ) were synthesized and characterized by elemental analysis, IR, 1 H NMR, 13 C NMR and ESI-MS. The cytotoxic activity in vitro of the ligand and complexes toward BEL-7402, A549, HeLa, HepG2 and MG-63 cell lines was evaluated using MTT method (MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Complexes 1 , 3 and 4 show moderate cytotoxic effect on the cell growth in BEL-7402 cells with IC 50 values of 32.1 ± 0.9, 37.9 ± 1.7 and 42.1 ± 3.0 μM, respectively. The apoptosis in BEL-7402 cell was investigated with AO/EB and Hoechst 33,258 staining methods. The autophagy in BEL-7402 cell induced by complexes was assayed using MDC staining cell nuclei. The cell invasion, reactive oxygen species (ROS), mitochondrial membrane potential, cell cycle arrest, cellular uptake, comet assay and wound healing were studied under a fluorescent microscope. The complexes can cause autophagy and inhibit the cell invasion, and increase the ROS levels and induce a decrease in the mitochondrial membrane potential. The expression of the proteins related with apoptosis induced by the complexes was assayed by western blot analysis. [ABSTRACT FROM AUTHOR]

Summary Pentostatin (PTN, deoxycoformycin) and arabinofuranosyladenine (Ara-A, vidarabine) are purine nucleoside antibiotics used clinically to treat hematological cancers and human DNA virus infections, respectively. PTN has a 1,3-diazepine ring, and Ara-A is an adenosine analog with an intriguing epimerization at the C-2′ hydroxyl group. However, the logic underlying the biosynthesis of these interesting molecules has long remained elusive. Here, we report that the biosynthesis of PTN and Ara-A employs an unusual protector-protégé strategy. To our surprise, we determined that a single gene cluster governs PTN and Ara-A biosynthesis via two independent pathways. Moreover, we verified that PenB functions as a reversible oxidoreductase for the final step of PTN. Remarkably, we provided the first direct biochemical evidence that PTN can protect Ara-A from deamination by selective inhibition of the host adenosine deaminase. These findings expand our knowledge of natural product biosynthesis and open the way for target-directed genome mining of Ara-A/PTN-related antibiotics. [ABSTRACT FROM AUTHOR]

The daily variations in circulating fatty acid (FA) contents and lipid metabolism have been well documented. However, whether long chain polyunsaturated FA (PUFA) contents and expression of genes involved in their de novo synthesis exhibit daily rhythms are yet unknown. We conducted the present study to investigate the daily variations in PUFA contents in plasma and liver of pigs. Moreover, diurnal expression of genes encode fatty acid desaturases and elongases, which are key enzymes catalyzed de novo synthesis of long chain PUFA, were also explored. The results showed that long chain PUFA contents in plasma and liver both exhibited diurnal rhythms. Diurnal variations were also observed in mRNA expression of FASD1 (Delta 5-desaturase), FASD2 (Delta 6-desaturase), ELOVL5 (fatty acid elongase 5) and ELOVL2 in liver, with an unexpectedly high level at night. Moreover, our results showed a similarity between the diurnal patterns of FASD1, FASD2, ELOVL2, ELOVL5 and Period 2. These results indicated a high activity of the desaturase-elongase pathway at night in pigs. These findings have important physiological and pathophysiological implications, since long chain PUFA are essential for cell function and closely involved in the development of metabolic syndrome. [ABSTRACT FROM AUTHOR]

As one of the major cell regulated center, mitochondria are closely associated with cell proliferation, apoptosis of tumor cell. In this work, four new ruthenium (II) polypyridyl complexes [Ru(bpy) 2 (FTTP)](ClO 4 ) 2 ( 1 ) (FTTP = 11-(3-fluoro-naphthalen-2-yloxy)-4,5,9,14-tetraaza-benzo[ b ]triphenylene, bpy = 2,2′-bipyridine), [Ru(phen) 2 (FTTP)](ClO 4 ) 2 ( 2 ) (phen = 1,10-phenanthroline), [Ru(bpy) 2 (PTTP)](ClO 4 ) 2 ( 3 ) (PTTP = 2-phenoxy-1,4,8,9-tetraazatriphenylene) and [Ru(phen) 2 (PTTP)](ClO 4 ) 2 ( 4 ) were synthesized and characterized by elemental analysis, ESI-MS, 1 H NMR and 13 C NMR. The cytotoxic activity, ability of inhibiting cell invasion, cell cycle arrest and apoptosis-inducing mechanism of these Ru(II) complexes have been investigated in detail by MTT (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide) method, invasion assay, comet assay as well as western blotting techniques. Notably, complexes 1 – 4 displayed high cytotoxic activity against liver carcinoma HepG2 cells and the IC 50 values of complexes 1 – 4 against HepG2 cells are 10.4 ± 1.2, 9.3 ± 0.6, 29.1 ± 1.5 and 5.6 ± 1.2 μM, respectively. The comet assay showed that the complexes can induce DNA damage. The acridine orange (AO) and ethidium bromide (EB) staining method indicated that the complexes can cause apoptosis in HepG2 cells. Further studies showed that complexes 1 – 4 caused cell cycle arrest at G0/G1 phase and induced HepG2 cells apoptosis through a ROS-mediated mitochondrial dysfunction pathway, which involved an increase in the levels of reactive oxygen species (ROS), a decrease in the mitochondrial membrane potential, activation of caspases and Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]

Summary Polyoxin, produced by Streptomcyes cacaoi var. asoensis and Streptomyces aureochromogenes , contains two non-proteinogenic amino acids, carbamoylpolyoxamic acid (CPOAA) and polyoximic acid. Although the CPOAA moiety is highly unusual, its biosynthetic logic has remained enigmatic for decades. Here, we address CPOAA biosynthesis by reconstitution of its pathway. We demonstrated that its biosynthesis is initiated by a versatile N -acetyltransferase, PolN, catalyzing L-glutamate ( 1 ) to N -acetyl glutamate ( 2 ). Remarkably, we verified that PolM, a previously annotated dehydrogenase, catalyzes an unprecedented tandem reduction of acyl-phosphate to aldehyde, and subsequently to alcohol. We also unveiled a distinctive acetylation cycle catalyzed by PolN to synthesize α-amino-δ-hydroxyvaleric acid ( 6 ). Finally, we report that PolL is capable of converting a rare sequential hydroxylation of α-amino-δ-carbamoylhydroxyvaleric acid ( 7 ) to CPOAA. PolL represents an intriguing family of Fe(II)-dependent α-ketoglutarate dioxygenase with a cupin fold. These data illustrate several novel enzymatic reactions, and also set a foundation for rational pathway engineering for polyoxin production. [ABSTRACT FROM AUTHOR]

The Bus Rapid Transit (BRT) system in New York City (NYC), called Select Bus Service (SBS), is a “light” BRT system with some but not all BRT features. Focusing on it, this study aims to contribute to a better understanding of riders' perceptions of BRT service implemented with limited space and capital funding. A total of 1700 SBS riders on four routes were interviewed using the survey methodology developed in this study. Statistical analysis and regression modeling were used to analyze rider socio-demographics, investigate the relationship between rider satisfaction levels, and the key factors driving them. The results show that, while most of them are transit dependent, new SBS riders are mainly attracted by better service and accessibility. Riders on different routes were found to have different socio-demographics. The statistical tests of satisfaction means provide further insight into the disparity in service evaluation between/among groups of riders (e.g. gender, experience, weather, route, trip purpose). Service frequency, speed, and on-time performance were found to have a positive influence on rider satisfaction across all routes. Variables related to off-board ticket machines and travel information are more valued than others. The effects of external factors vary according to characteristics of the routes and rider groups. This study suggests potential applications of the results for future planning and improvement to increase rider satisfaction and thereby retain and increase ridership. [ABSTRACT FROM AUTHOR]

Dysfunction of energy metabolism can be a significant and fundamental pathophysiological basis for strokes. In studies of both humans and rodents, resveratrol, a natural polyphenol, has been reported to provide protection from cerebral ischemic injury by regulating expression of silent mating type information regulation 2 homolog 1 (SIRT1). However, direct evidence demonstrating that resveratrol exerts neuroprotection from cerebral ischemia injury by decreasing energy consumption is still lacking. Therefore, the aim of this study was to elucidate the mechanisms and signaling pathways through which resveratrol regulates energy metabolism in the ischemic brain, and to identify potential targets of resveratrol. ATP levels in brain tissues were detected by high performance liquid chromatography. SIRT1 and the phosphorylation of adenosine-monophosphate-activated protein kinase (P-AMPK) expressiones were evaluated by western blot. Levels of phosphodiesterase (PDEs) and cAMP were quantitated by real-time PCR and ELISA, respectively. Results showed that resveratrol significantly reduced the harmful effects of cerebral ischemic injury in vivo. Moreover, levels of ATP, p-AMPK, SIRT1, and cAMP were increased by resveratrol and PDE inhibitors. In conclusion, our findings indicate that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the antinociception of spirocyclopiperazinium salt compound LXM-10-M (2,4-dimethyl-9-β-m-hydroxyphenylethyl-3-oxo-6, 9-diazaspiro [5.5] undecane chloride) in thermal and chemical pain models, and further to explore the molecular target and potential signal pathway. We assessed the antinociception of LXM-10-M in hot-plate test, formalin test and acetic acid writhing test in mice. The possible changes of calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)/cAMP response element-binding protein (CREB)/calcitonin gene related peptide (CGRP) signaling pathway were detected by Western Blot in mice. Administration of LXM-10-M produced significant antinociception in hot-plate test, formalin test and acetic acid writhing test in mice, with no obvious toxicity. The antinociceptive effects were blocked by pretreatment with methyllycaconitine citrate (MLA, α7 nicotinic receptor antagonist) or tropicamide (TRO, M4 muscarinic receptor antagonist). Western blot analysis showed that the upregulations of p-CaMKIIα, p-CREB and CGRP in the spinal cord were reduced by LXM-10-M in chemical pain model in mice, and the effects were blocked by MLA or TRO pretreatment. This is the first paper to report that LXM-10-M exerted significant antinociception, which may be attributed to the activation of α7 nicotinic receptor and M4 muscarinic receptor and thereby triggering the inhibition of CaMKIIα/CREB/CGRP signaling pathway in mice. [ABSTRACT FROM AUTHOR]

Iron is an essential trace element that is vital important in various biological process. A deficiency in iron could induce public health problem e.g. anaemia, while an overload could induce ROS production, lipid peroxidation and DNA bases modifications. In the present study, a new iron fortifier was synthesized, and its acute/sub-acute toxicity was investigated. According to the improved Karber's method, the median lethal dose (LD 50 ) of the ferrous N-carbamylglycinate in SD rat was 3.02 g/kg and the 95% confidence intervals were between 2.78 and 3.31 g/kg. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, organ weights, histopathology, ophthalmology, hematology, and clinical chemistry parameters in any of the treatment groups of ferrous N-carbamylglycinate at target concentrations corresponding to 150, 300, and 600 mg/kg/day for 28 days. The no observed adverse effect level (NOAEL) for ferrous N-carbamylglycinate was at least 600 mg/kg b.w. day in rats. In addition, no evidence of mutagenicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that ferrous N-carbamylglycinate is a low-toxic substance with no genotoxicity. [ABSTRACT FROM AUTHOR]

Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The mechanism of its adrenal toxicity is far from clear. This study was conducted to estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B-QCT) metabolite and to further investigate their mechanisms. Following doses of QCT increasing from 5 to 50 μM, cell apoptosis and necrosis, mitochondrial dysfunction and redox imbalance were observed in porcine adrenocortical cells. The mRNA levels of the six components of intermediary enzymes and the adrenal renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by QCT, indicating that QCT might influence aldosterone secretion not only through the upstream of the production but also through the downstream of the adrenal RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis, mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis showed that no desoxy metabolites of QCT were found in either cell lysate or supernatant samples. In conclusion, we reported on the cytotoxicity in porcine adrenocortical cells exposed to QCT via oxidative stress, which raised awareness that its toxic effects resulted from N→O groups, and its toxic mechanism might involve the interference of the steroid hormone biosynthesis pathway. [ABSTRACT FROM AUTHOR]

N -carbamylglutamate (NCG) is a metabolically stable analog of N -acetylglutamate that activates carbamyl phosphate synthase-1, a key arginine synthesis enzyme in enterocytes. It is a promising feed additive in swine in China. In this study, we assessed the acute and sub-acute toxicity of NCG in Sprague–Dawley (SD) rats. All rats survived until they were killed at a scheduled time point. No adverse effects or mortality was observed following acute oral administration of 5000 mg/kg NCG to SD rats. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, a functional observational battery, organ weights, histopathology, ophthalmology, hematology, coagulation, and clinical chemistry parameters in any of the treatment groups in sub-acute doses of NCG at target concentrations corresponding to 500, 2000, and 3000 mg/kg/day for 28 days neither. In addition, no evidence of mutagenicity or genotoxicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that NCG is a non-toxic substance with no genotoxicity. [ABSTRACT FROM AUTHOR]

Two new supramolecular compounds were synthesized and characterized with the formula of [Cu(bipy)(OAc)]·(DBrS)·5HO 1, [Co(phen)(CO)]·(DBrS)·5HO 2 (HDBS = meso-2,3-dibromosuccinic acid; bipy = 2,2'-bipyridine; phen = 1,10-phenanthroline). The crystal structures of complexes were determined by X-ray single-crystal diffraction. Complex 1 represents R6 water clusters and complex 2 stabilizes in a 1D water tape notated T4(2)6(2). For 2, the 2D layer is defined as a 2D (3,4,6)-connected network with the Schläfli symbol of (4·5·6)(4·5·6·7)(4·5)(4·5·6·7·9). Results about i.r. spectra and elemental analyses are presented. [ABSTRACT FROM AUTHOR]

• Microbial controlling HO• production at soil-water interfaces was studied. • Microbial communities drive HO• generation mainly via Fe redox cycling. • K82, Geobacter, Paucimonas and Desulfotomaculum are key genera for HO• production. • The discrepancies of genera well interpreted the HO• production in soil slurries. The generation of reactive oxygen species (ROS) mediated by minerals and/or microorganisms plays a vital but underappreciated role in affecting carbon and nutrient cycles at soil-water interfaces. It is currently unknown which interactions between microbial communities and iron (Fe) minerals produce hydroxyl radical (HO•), which is the strongest oxidant among ROS. Using a series of well-controlled anoxic incubations of soil slurries, we demonstrated that interactions between microbial communities and Fe minerals synergistically drove HO• production (up to ∼100 nM after 21-day incubation). Microorganisms drove HO• generation in anoxic environments predominantly by modulating iron redox transformation that was more prominent than direct production of ROS by microorganisms. Among the microbial communities, Geobacter, Paucimonas, Rhodocyclaceae_K82 , and Desulfotomaculum were the key genera strongly affecting HO• production. In manured soils, the former two species had higher abundances and were crucial for HO• production. In contrast, the latter two species were mainly abundant and important in soils with mineral fertilizers. Our study suggests that abundant highly reactive oxidant HO• can be generated in anoxic environments and the microbial community-mediated redox transformations of iron (oxyhydr)oxides may be responsible for the HO• production. These findings shed light on the microbial generation of HO• in fluctuating redox environments and on consequences for global C and nutrient cycling. [Display omitted] [ABSTRACT FROM AUTHOR]

Two metal oxygen connectivities Cu(II) complexes [Cu(HO)( μ-OH)( μ-OAc)(DBrS)]⋅4HO 1 and [Cu(HO)(DBrS)](DBrS)⋅4HO 2 have been synthesized (HDBrS = HOOC-(CHBr)-COOH, DBrS= (3a R,6a S)-3a,6a-dibromo-3,6-dioxohexahydrofuro[3,4- c]furan-1,4-bis(olate)). Within 1, two CuO square pyramid are edge-shared to generate di-square pyramids, each of which are corner-shared to one another CuO octahedron to form polyhedral copper oxygen chains. The resulted polynuclear single chains are bridged by meso-2,3-dibromossuccinate anions to generate 2D layers. Compound 2 features a trimer polyhedrons unit with two CuO square pyramid and CuO octahedron, which are further interconnected by meso-2,3-dibromossuccinate anions into 3D coordination polymer. The study of magnetic property indicates that antiferromagnetic coupling interactions exist between the adjacent Cu(II) ions. [ABSTRACT FROM AUTHOR]

Two coordination polymers, Cu(bipy)(DBrS) 1 and Co(bipy)(HO)(DBrS) 2 with bipy = 2,2′-bipyridine, HDBrS = meso-2,3-dibromosuccinic acid represent rare examples of metal complexes with meso-2,3-dibromosucciniato ligand. Within 1, the CuNO octahedra are interlinked by DBrS anions in a μ- κΟΟ′: κΟ″Ο″′ coordination mode to form $${}_{\infty }^{1}$$ [Cu(bipy)(DBrS)] chains, which are further assembled into 2D supramolecular layers by interchain π···π stacking interactions. In 2, the six-coordinated Co ions are bridged by DBrS anions in a μ- κΟ: κΟ′ fashion to form $${}_{\infty }^{1}$$ [Co(bipy)(HO)(DBrS)] polymer chains and the adjacent 1D chains interconnected by weak C-H···O hydrogen bonds to construct 2D supramolecular layers. The temperature-dependent magnetic susceptibility shows that 2 obeys Curie-Weiss law χ = C/( T − Θ) with C = 2.16 cm K mol and Θ = −0.40 K and the best fit gave a weak antiferromagnetic coupling ( J = −0.89 cm) among Co ions. Results about infrared spectra and elemental analyses are also presented. Graphical Abstract: In the present paper, we have discussed the syntheses and crystal structures of two metal-organic based 1D polymers of Cu(II) and Co(II) respectively, and magnetic behavior in the temperature range 2-300 K of the Co(II) compound. The compounds feature 1D chains based on bridging dibromosucciniato. The Cu(II) compound represents the first example of meso-2,3-dibromosuccinic acid coordination polymers that exhibit μ- κΟΟ′: κΟ″Ο″′ coordination mode.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

HER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14–3–3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too. Immunohistochemistry experiment was performed to detect expression status of 14–3–3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC. The positive expression rates of 14–3–3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14–3–3ζ was significantly increased in ADH, DCIS and IDC groups. 14–3–3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14–3–3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14–3–3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14–3–3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14–3–3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14–3–3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14–3–3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively. 14–3–3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14–3–3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14–3–3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis. • 14-3-3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC. • Combined detection of 14-3-3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis. • In IDC cases with 14-3-3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased, while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis. [ABSTRACT FROM AUTHOR]

In this study, we present a rapid and simple method for the separation and direct detection of glutathione by combining gold nanoparticles and MALDI- TOF-MS with graphene as matrix. Gold nanoparticles enable the selective capture of thiol-containing compounds. Gold nanoparticles bound with analytes can be mixed with graphene matrix for direct analysis by MALDI- TOF-MS, which can avoid sample loss and contamination during transfer process. Compared with a conventional matrix, α-cyano-4-hydroxycinnamic acid, graphene exhibits an excellent desorption/ionization efficiency, thermal and mechanical properties. The use of graphene as matrix avoids the fragmentation of analytes. Stable analysis was achieved with less background interference even at the concentration of 0.625 ng/μ L. To further confirm its efficiency, the optimized approach was applied to the separation and detection of glutathione in mouse liver extraction. This result showed the great potential of detection of biologically important thiols in biochemical and biomedical research. [ABSTRACT FROM AUTHOR]

Abstract: The halocarbons studied here are chemicals controlled in the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer and its Amendments, which have both high ozone depleting potentials (ODPs) and high global warming potentials (GWPs). These halocarbons are mainly used for refrigeration, air-conditioning, foam blowing, tobacco expansion, aerosol propulsion, solvent cleaning, and fire fighting. China ratified the Montreal Protocol in 1991 and has been implementing the phase-out of halocarbons since then. In this paper, the emissions of halocarbons from China were estimated for 1995–2024 based on the historical consumption, the country program for complying with the Montreal Protocol, and the sector plans for phasing out halocarbons. The results show that China''s compliance with the Montreal Protocol contributes greatly to both ozone protection and climate protection. [Copyright &y& Elsevier]

Introduces a high-accuracy discrete singular convolution for the numerical simulation of convective heat transfer problems. Solutions for the bouyancy-driven cavity; Quasi-wavelet-based discrete singular convolution approach; Standard form of the Galerkin finite-element method.

• Naphthalimide-based a lysosome-targeting fluorescent probe LyNP-H 2 S for H 2 S sensing. • LyNP-H 2 S displays a significant 262-fold fluorescence intensity enhancement in the presence of H 2 S at 540 nm. • Moreover, LyNP-H 2 S can rapid image H 2 S in lysosome and inflamed tissues. Since the fluctuation of cellular hydrogen sulfide (H 2 S) is a very important third endogenously generated gaseous signaling molecule and plays a key role in the development of numerous human disorders, the real-time fluorescence detection of H 2 S in living systems has attracted plenty of interest during past decade. Although a lot of H 2 S fluorescent probes have been reported, the relationship between the physiology and pathology of H 2 S in organelles remains unclear, especially for inflammatory tissue. In this work, by adopting a weakly basic morpholine group as the lysosome-targeting site, a naphthalimide derivative as the signal reporter group and a 4-dinitrobenzene-ether (DNB) as fluorescence signal quencher and H 2 S-selective recognition moiety, we reported a new lysosome-targeting TP fluorescent probe LyNP-H 2 S for H 2 S detection and imaging in living cells and inflamed tissues. The probe LyNP-H 2 S exhibits very low fluorescence signal in the absence of H 2 S, and displays a significant 262-fold fluorescence intensity enhancement in the presence of H 2 S at 540 nm. Moreover, LyNP-H 2 S has the capability of quantitative detection of H 2 S at concentrations ranging from 0 to 12.0 μM (limit of detection = 9.8 nM), rapid response, as well as high sensitivity and selectivity toward H 2 S. Impressively, the results of living cell and inflamed tissues imaging test demonstrate that LyNP-H 2 S has the potentiality of being an ideal probe for real-time H 2 S detection in biosystems. [ABSTRACT FROM AUTHOR]

Simple Summary: Iron deficiency is a serious nutrient deficiency in neonatal pigs during the suckling period in modern intensive farming systems and leads to impaired immune response, infection risks, and retardation of growth. The objective was to determine how iron deficiency in neonatal pigs alters the serum metabolomic profile using quantitative and qualitative analysis by ultra-performance liquid chromatography-tandem mass spectrometer (UPLCMS/MS). The current results revealed that iron deficiency led to a series of metabolic changes involved in tyrosine metabolism, phenylalanine metabolism, bile secretion, primary bile acid biosynthesis, steroid biosynthesis, and upregulated activities of the urea cycle enzymes in the liver of neonatal piglets. Few studies focused on the effects of iron on characterizing alterations of metabolic processes in neonatal piglets. In the present study, 16 neonatal piglets were randomly assigned to two groups. In the first group piglets were given an intramuscularly injection of iron dextran at 150 mg as a positive control (CON) and the second group were not supplemented with iron as a negative control for iron deficiency (ID). At day 8, iron status, serum biochemical parameters, serum metabolome, hepatic histology, and hepatic expression of genes for the metabolism were analyzed. Results indicated that piglets without iron supplementation had significantly reduced iron values and increased blood urea nitrogen concentrations at day 8 (p < 0.05). Analysis of serum metabolome revealed that concentrations of serum lysine, leucine, tyrosine, methionine, and cholesterol were significantly decreased while concentrations of 3-Methyldioxyindole, chenodeoxycholate acid, indoleacetic acid, icosadienoic acid, phenylpyruvic acid, pantothenic acid, ursocholic acid, and cholic acid were significantly increased in iron deficient piglets (p < 0.05). Furthermore, expressions of cyp7a1 and the urea cycle enzyme (ornithinetranscarbamoylase and argininosuccinate synthetase) were significantly increased in iron deficient pigs (p < 0.05). The present experimental results indicated that neonatal piglets without iron supplementation drop to borderline anemia within 8 days after birth. Iron deficiency led to a series of metabolic changes involved in tyrosine metabolism, phenylalanine metabolism, bile secretion, primary bile acid biosynthesis, steroid biosynthesis, and upregulated activities of the urea cycle enzymes in the liver of neonatal piglets, suggesting early effects on metabolic health of neonatal piglets. [ABSTRACT FROM AUTHOR]

Erosion of freeze-thaw soil by meltwater from snow/glacier is one of the main erosion types in high altitude or latitude regions. This study aims to experimentally measure soil erosion processes over partially-unfrozen soil slopes in laboratory. The experiments including three slope gradients of 10°, 15°, and 20°, three water flow rates of 1, 2, and 4 L/min (0.06, 0.12, and 0.24 m3/h), and three thawed-soil depths of 1, 2, and 5 cm were conducted to measure sediment concentration and calculate its delivery rate under seven slope lengths of 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, and 6.0 m. The sediment delivery rates from nonfrozen soil slopes under the corresponding slope gradients, flow rates, and slope lengths also were measured as control treatments. Results showed that the sediment delivery rate from both partially-unfrozen and nonfrozen soil slopes increased logarithmically with slope length. The sediment delivery rate from partially-unfrozen soil slope increased with the increased slope gradient and meltwater flow rate significantly, and the effect of water flow rate on it was greater than that of slope gradient. The thawed-soil depth did not significantly affect sediment delivery rate. The sediment delivery rate from a partially-unfrozen loamy soil slope averagely was 11.4% smaller than that from nonfrozen soil slope. This study is helpful to understand the erosion process of thawing-soil by meltwater from snow/glacier. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to discover the effects of iron on the intestinal development and epithelial maturation of suckling piglets. Twenty-seven newborn male piglets from 9 sows (3 piglets per sow), with similar body weight, were selected. The 3 piglets from the same sow were randomly divided into 1 of the 3 groups. The piglets were orally administrated with 2 mL of normal saline (CON group) or with 25 mg of iron by ferrous sulfate (OAFe group; dissolved in normal saline) on the 2nd, 7th, 12th, and 17th day, respectively, or intramuscularly injected with 100 mg of iron by iron dextran (IMFe group) on the 2nd day. The slaughter was performed on the 21st day and intestinal samples were collected. Compared with the CON group, iron supplementation significantly increased the length (P < 0.001), weight (P < 0.001), relative weight (P < 0.001), and the length:weight ratio (P < 0.001) of the small intestine in both OAFe and IMFe groups. The villus height (P < 0.001), crypt depth (CD) (P < 0.001), villus width (P = 0.002), and surface area (P < 0.001) in the jejunum of IMFe and OAFe piglets were also greater than those in CON piglets. The mRNA expression of trehalase (Treh ; P = 0.002) and sucrase isomaltase (Sis ; P = 0.043), markers of epithelial maturation, increased in OAFe and IMFe piglets, respectively. Moreover, enterocyte vacuolization, observed in fetal-type enterocyte, was reduced in OAFe and IMFe piglets, compared with CON piglets. However, no significant difference in the expression of the target genes of wnt/β-catenin signaling pathway was observed. The results indicated that both oral administration and intramuscular injection with iron promoted intestinal development and epithelial maturation in suckling piglets and that the effects of iron may be independent of wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Whether methionine content and its metabolites in liver and skeletal muscle show diurnal rhythmicity remains unknown. In the present study, we investigated the diurnal rhythms in methionine and S-adenosylmethionine (SAM) in plasma, liver, and longissimus thoracis muscle, as well as in enzymes involved in methionine-related transmethylation reaction using pigs maintained in a 12-h photoperiod. The results showed that concentration of methionine and SAM, as well as mRNA expression of methionine adenosyltransferase (MAT1A), DNA methyltranferase (DNMT3A and DNMT3B) in liver showed diurnal rhythmicity. Comparison with typical circadian clock genes revealed a similarity between the diurnal patterns of MAT1A and cryptochrome circadian clock 1 (CRY1) expression, whereas the daily patterns of MAT2A, DNMT3A, and DNMT3B expression were reversely related to the expression patterns of Timeless. These results imply that much attention should be paid to rhythms of methionine metabolism and methylation activity in the pathogenesis of diseases, such as cancer and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Probiotics confer immunological protection to the host through the regulation, stimulation, and modulation of immune responses. Researchers have shifted their attention to better understand the immunomodulatory effects of probiotics, which have the potential to prevent or alleviate certain pathologies for which proper medical treatment is as yet unavailable. It has been scientifically established that immune cells (T- and B-cells) mediate adaptive immunity and confer immunological protection by developing pathogen-specific memory. However, this review is intended to present the recent studies on immunomodulatory effects of probiotics. In the early section of this review, concepts of probiotics and common probiotic strains are focused on. On a priority basis, the immune system, along with mucosal immunity in the human body, is discussed in this study. It has been summarized that a number of species of Lactobacillus and Bifidobacterium exert vital roles in innate immunity by increasing the cytotoxicity of natural killer cells and phagocytosis of macrophages and mediate adaptive immunity by interacting with enterocytes and dendritic, Th1, Th2, and Treg cells. Finally, immunomodulatory effects of probiotics on proinflammatory and anti-inflammatory cytokine production in different animal models have been extensively reviewed in this paper. Therefore, isolating new probiotic strains and investigating their immunomodulatory effects on cytokine profiles in humans remain a topical issue. [ABSTRACT FROM AUTHOR]

Neuronal-regulated cell death (RCD) due to the accumulation of ROS within the central nervous system (CNS) is one of the crucial causes of central system diseases. Caspase-dependent apoptosis is the only form of RCD. As research progressed, several nonapoptotic cell death pathway RCDs were identified. Ferroptosis is a nonapoptotic RCD characterized by lipid peroxidation and plasma membrane damage. Polygonatum cyrtonema Hua. Polysaccharides (PCP) are an effective antioxidant. Based on this, the protective effect and mechanism of PCP against H2O2-induced microglial injury were investigated. Furthermore, the protective mechanism of PCP against ferroptosis in microglia was explored. Our results indicated that PCP could reduce oxidative stress-induced ROS accumulation by activating the NRF2/HO-1 signaling pathway, thus attenuating RCD in microglia. Subsequent studies have revealed that PCP alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. Therefore, we hypothesized that PCP exerts antioxidative and anti-ferroptosis effects by activating the expression of the NRF2/HO-1 pathway. This facilitates new ideas for clinically effective prevention and treatment of diseases due to accumulated reactive oxygen species in the CNS. Simultaneously, PCP has the development potential as a new drug candidate for treating CNS diseases. [ABSTRACT FROM AUTHOR]

Methionine restriction (MR) exerts many beneficial effects, such as increasing longevity, decreasing oxidative damage and alleviating inflammatory responses. Much attention has been recently focused on the effects of MR on metabolic health, especially lipid metabolism, since the increasing incidence of obesity, insulin resistance and type 2 diabetes causes a worldwide health problem. In general, MR is considered to increase de novo lipogenesis, lipolysis and fatty acid oxidation, with a result of reduced fat accumulation. However, different responses in lipid metabolism between adipose tissue and liver are declared. Therefore, in this review, we will focus on the changes of lipid metabolism responses to dietary MR. Moreover, the comparison of alterations of fat metabolism responses to dietary MR between adipose tissue and liver, and the comparison of changes between rodents and pigs is made to illustrate the tissue- and species-specific responses. In addition, the possible mechanisms that might be engaged in the regulation of MR diet on lipid metabolism are also discussed. [ABSTRACT FROM AUTHOR]

Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn contaminants. FBs could cause a variety of diseases in animals and humans, such as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals. To date, almost no review has addressed the toxicity of FBs in relation to oxidative stress and their metabolism. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for FB-induced toxicity as well as the metabolism. The present review showed that studies have been carried out over the last three decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of FBs treatment and have correlated them with various types of FBs toxicity, indicating that oxidative stress plays critical roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis, acylation and transamination. Ceramide synthase, carboxylesterase FumD and aminotransferase FumI could degrade FB and FB. The cecal microbiota of pigs and alkaline processing such as nixtamalization can also transform FB into metabolites. Most of the metabolites of FB were less toxic than FB, except its partial (pHFB) metabolites. Further understanding of the role of oxidative stress in FB-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of metabolism and the metabolizing enzymes of FBs. The present review might contribute to reveal the toxicity of FBs and help to protect against their oxidative damage. [ABSTRACT FROM AUTHOR]

As an emerging contaminant, tungsten's distribution and speciation in soils are far from understood. In this study, two soil profiles near a typical abandoned tungsten smelter in Hunan Province, China were collected and investigated, to ascertain the binding and association of tungsten with different soil components and subsequently to understand its mobility. The data showed that past tungsten smelting activities resulted in elevated concentrations of both tungsten and arsenic in the soil profiles, both of which ranged from dozens of to a few hundred mg/kg. Nano-scale secondary ion mass spectrometry (NanoSIMS) was employed to quantify the distribution and association of tungsten with various other elements. Combined with sequential extraction and mineralogical analysis, the data from NanoSIMS showed that aluminosilicates including kaolinite and illite were the most important mineral hosts for tungsten, whereas arsenic was predominantly bound to iron (oxyhydr)oxides. Additional data from 13C nuclear magnetic resonance and X-ray photoelectron spectroscopy revealed that soil organic matter retained tungsten in deep soils (>70 cm) by binding tungsten through carboxyls on aromatic rings. Compared to arsenic, tungsten migrated deeper in the soil profiles, suggesting its higher mobility and potential risk to groundwater quality. [Display omitted] • Tungsten migrated deeper in the soil profiles than arsenic. • Aluminosilicates were the most important mineral hosts for tungsten. • Soil organic matter (SOM) was an essential reservoir for tungsten in deep soil. • Carboxyls on aromatic rings played a major role in tungsten complexation with SOM. [ABSTRACT FROM AUTHOR]

T-2 toxin, a major compound of trichothecenes, inhibits protein synthesis and induces inflammation and cell apoptosis through the activation of MAPK pathway. The JAK/STAT pathway has recently been shown to be downstream targets of trichothecenes. However, whether there is any crosstalk between JNK and JAK/STAT pathways in trichothecene toxicity has not been studied. In the present study, we explored this potential in RAW264.7 cells treated with T-2 toxin. Our results revealed a crosstalk between JNK1 and STAT3 after T-2 toxin treatment, which was mediated by K-Ras. T-2 toxin treatment resulted in rapid phosphorylation, and more importantly, JNK1-STAT3 signaling pathway was shown to maintain the normal function of the mitochondria and to inhibit T-2 toxin-induced apoptosis. Therefore, this pathway was considered to be a potential cell survival pathway. Breakdown and degranulation of ribosomes in the rough endoplasmic reticulum and swelling of mitochondria were clearly visible after the cells had been incubated with T-2 toxin for 12 h. Our data suggest that T-2 toxin had a Janus face: it induced both apoptotic and cell survival pathways. These results suggest that the crosstalk and the balance between MAPK and JAK/STAT pathway might be involved in T-2 toxin-induced apoptosis in RAW264.7 cells. [ABSTRACT FROM AUTHOR]

Cordyceps is a large group of entomogenous, medicinally important fungi. In this study, we sequenced, assembled, and annotated the entire mitochondrial genome of Ophiocordyceps xuefengensis, in addition to comparing it against other three complete cordyceps mitogenomes that were previously published. Comparative analysis indicated that the four complete mitogenomes are all composed of circular DNA molecules, although their sizes significantly differ due to high variability in intron and intergenic region sizes in the Ophiocordyceps sinensis and O. xuefengensis mitogenomes. All mitogenomes contain 14 conserved genes and two ribosomal RNA genes, but varying numbers of tRNA introns. The Ka/Ks ratios for all 14 PCGs and rps3 were all less than 1, indicating that these genes have been subject to purifying selection. Phylogenetic analysis was conducted using concatenated amino acid and nucleotide sequences of the 14 PCGs and rps3 using two different methods (Maximum Likelihood and Bayesian analysis), revealing highly supported relationships between O. xuefengensis and other Ophiocordyceps species, in addition to a close relationship with O. sinensis. Further, the analyses indicated that cox1 and rps3 play important roles in population differentiation. These mitogenomes will allow further study of the population genetics, taxonomy, and evolutionary biology of medicinally important cordyceps species. [ABSTRACT FROM AUTHOR]