A true response of the brain network during electroacupuncture stimulation at scalp acupoints: An fMRI with simultaneous EAS study.

OBJECTIVES: The aim of this study was to explore simultaneous brain network responses to electroacupuncture stimulation (EAS) at scalp acupoints by accounting for placebo effects. MATERIALS AND METHODS: Sixty healthy subjects were recruited and randomly divided into two groups: Group 1 and Group 2. Functional magnetic resonance imaging (fMRI) was performed in Group 1 with sham acupuncture stimulation at acupoints Shenting (GV24) and Touwei (ST8) without EAS. Group 2 underwent verum EAS at the same acupoints during fMRI. Independent component analysis was used to analyze the fMRI data. Full-factor statistical analysis was used to compare the differences in fMRI data between the two groups and evaluate the changes in functional connectivity in brain networks after verum electrical stimulation (Group 1 [after sham electrical current stimulation - before sham electrical current stimulation] - Group 2 [after verum electrical current stimulation - before verum electrical current stimulation]) (p <.001, extent threshold k = 20 voxels). RESULTS: Six brain networks were identified. Significant increased functional connectivity was observed in the right and left executive control networks, sensorimotor network, and attention network, while decreased functional connectivity was mainly found in the default mode network. There were no statistically significant differences in the salience network. CONCLUSIONS: fMRI with simultaneous EAS provides a method to explore brain network responses due to EAS at scalp acupoints. The networks responsible for cognition are differentially activated by EAS in a coordinated manner.

Electroacupuncture Synergistically Inhibits Proinflammatory Cytokine Production and Improves Cognitive Function in Rats with Cognitive Impairment due to Hepatic Encephalopathy through p38MAPK/STAT3 and TLR4/NF-κB Signaling Pathways.

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. METHODS: Fifty Wistar rats were randomly divided into a normal group (n = 10) and model group (n = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl4) and treatment groups including EA group (CCl4 + EA), lactulose group (CCl4 + Lac), and EA plus lactulose group (CCl4 + CM), with 9 rats in each group. At the end of the 9th week, rats in CCl4 + Lac and CCl4 + CM groups had lactulose gavage at a dose of 10 mL/kg body weight, while normal control and CCl4 groups had gavage with the same volume of normal saline once a day for 21 days until the end of the experiment. Rats in CCl4 + EA and CCl4 + CM groups underwent acupuncture at Baihui (GV[DU]20), Shenting (GV[DU]24), and Zusanli (ST36) acupoints, among which EA at Baihui and Shenting acupoints were given once daily for 30 min lasting for 21 consecutive days. The effect of the treatment was measured by the Morris water maze test for learning and memory ability and magnetic resonance spectroscopy (MRS) for neuronal metabolism in the hippocampus of rats with hepatic encephalopathy. Pathological change in the rat hippocampus was observed by HE staining, while serum ammonia and liver function markers were detected. Western blot and real-time fluorescent quantitative PCR were used to detect the expressions of specific genes and proteins in the brain tissue. RESULTS: Compared with those in the control group, rats undergoing EA had significantly shortened escape latency and increased number of platform crossing. H&E staining confirmed that EA improved brain tissue necrosis and ameliorated nuclear pyknosis in rats with hepatic encephalopathy. Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB). In addition, EA inhibited the brain expressions of TNF-α, IL-1ß, IL-6, iNOS, TLR4, MyD88, NF-κB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-α, IL-6, TLR4, MyD88, NF-κB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3. MRS showed increased Glx/Cr and decreased NAA/Cr, Cho/Cr and mI/Cr in the control group, and EA significantly reversed such changes in Glx/Cr and mI/Cr values. CONCLUSION: EA ameliorated the production of excessive proinflammatory cytokines in the hippocampus of rats with cognitive dysfunction secondary to hepatic encephalopathy, which also gave rise to subsequent changes such as reduced blood ammonia level, brain-protective activated astrocytes, and lower degree of brain tissue injury. The p38MAPK/STAT3 and TLR4/MyD88/NF-κB signaling pathways may be involved. EA can also improve the metabolism of NAA and Cho in the rat hippocampus and thereby improve learning and memory abilities.

Magnetic resonance quantitative susceptibility mapping in the evaluation of hepatic fibrosis in chronic liver disease: a feasibility study.

BACKGROUND: Noninvasive methods for the early diagnosis and staging of hepatic fibrosis are needed. The present study aimed to investigate the alteration of magnetic susceptibility in the liver of patients with various fibrosis stages and to evaluate the feasibility of using susceptibility to stage hepatic fibrosis. METHODS: A total of 30 consecutive patients with chronic liver diseases (CLDs) underwent magnetic resonance imaging (MRI) and liver biopsy evaluation of hepatic fibrosis, necroinflammatory activity, iron load, and steatosis. Quantitative susceptibility mapping (QSM), R2* and proton density fat fraction (PDFF) images were postprocessed from the same gradient-echo data for quantitative tissue characterization using region of interest (ROI) analysis. The differences for MRI measurements between cohorts of non-significant (Ishak-F <3) and significant fibrosis (Ishak-F ≥3) and the correlation of MRI measurements with fibrosis stages and necroinflammatory activity grades were tested. Receiver operating characteristic (ROC) analysis was also performed. RESULTS: There was a significant difference in liver susceptibility between the cohorts of significant and non-significant fibrosis (Z=-2.880, P=0.004). A moderate negative correlation between the stages of liver fibrosis and liver susceptibility was observed (r=-0.471, P=0.015). Liver magnetic susceptibility differentiated non-significant from significant hepatic fibrosis with an area under the receiver operating curve (AUC) of 0.836 (P=0.004). A highly sensitive diagnostic performance with an AUC of 0.933 was obtained using magnetic susceptibility and PDFF together (P<0.001). CONCLUSIONS: A noninvasive liver QSM-based evaluation promises an accurate assessment of significant fibrosis in patients with CLDs.

Transcriptomic analysis reveals key factors in fruit ripening and rubbery texture caused by 1-MCP in papaya.

BACKGROUND: Ethylene promotes fruit ripening whereas 1-methylcyclopropene (1-MCP), a non-toxic antagonist of ethylene, delays fruit ripening via the inhibition of ethylene receptor. However, unsuitable 1-MCP treatment can cause fruit ripening disorders. RESULTS: In this study, we show that short-term 1-MCP treatment (400 nL•L- 1, 2 h) significantly delays papaya fruit ripening with normal ripening characteristics. However, long-term 1-MCP treatment (400 nL•L- 1, 16 h) causes a "rubbery" texture of fruit. The comparative transcriptome analysis showed that a total of 5529 genes were differently expressed during fruit ripening compared to freshly harvested fruits. Comprehensive functional enrichment analysis showed that the metabolic pathways of carbon metabolism, plant hormone signal transduction, biosynthesis of amino acids, and starch and sucrose metabolism are involved in fruit ripening. 1-MCP treatment significantly affected fruit transcript levels. A total of 3595 and 5998 differently expressed genes (DEGs) were identified between short-term 1-MCP, long-term 1-MCP treatment and the control, respectively. DEGs are mostly enriched in the similar pathway involved in fruit ripening. A large number of DEGs were also identified between long-term and short-term 1-MCP treatment, with most of the DEGs being enriched in carbon metabolism, starch and sucrose metabolism, plant hormone signal transduction, and biosynthesis of amino acids. The 1-MCP treatments accelerated the lignin accumulation and delayed cellulose degradation during fruit ripening. Considering the rubbery phenotype, we inferred that the cell wall metabolism and hormone signal pathways are closely related to papaya fruit ripening disorder. The RNA-Seq output was confirmed using RT-qPCR by 28 selected genes that were involved in cell wall metabolism and hormone signal pathways. CONCLUSIONS: These results showed that long-term 1-MCP treatment severely inhibited ethylene signaling and the cell wall metabolism pathways, which may result in the failure of cell wall degradation and fruit softening. Our results reveal multiple ripening-associated events during papaya fruit ripening and provide a foundation for understanding the molecular mechanisms underlying 1-MCP treatment on fruit ripening and the regulatory networks.

Synthesis and Characterization of Constrained Geometry Oxygen and Sulphur Functionalized Cyclopentadienylchromium Complexes and Their Use in Catalysis for Olefin Polymerization.

A series of constrained geometry O-functionalized cyclopentadienylchromium complexes (1-6) and a S-functionalized cyclopentadienylchromium complex (7) were first synthesized, characterized, and tested as catalyst precursors for the olefin polymerization. In the presence of MAO, the complexes exhibited high catalytic activity for the polymerization of ethylene. It is shown that ligand variations can have a substantial effect on catalyst activity and stability. The effect of Al/Cr ratio on catalytic activity was also studied.

Zirconium and hafnium complexes supported by linked bis(beta-diketiminate) ligands: synthesis, characterization and catalytic application in ethylene polymerization.

Zirconium and hafnium complexes bearing new 1,2-ethanediyl- or 1,3-propanediyl-linked bis(beta-diketiminate) ligands, [{C(n)H(2n)-(BDI(Ar))(2)}MCl(2)] (Ar = 2,6-Me(2)-C(6)H(3), 2,6-Cl(2)-C(6)H(3), 2,6-(i)Pr(2)-C(6)H(3); M = Zr, n = 2 (4a-c), n = 3 (5a-c); M = Hf, n = 2 (6b)), were synthesized via the reaction of MCl(4).2THF and one equivalent of dilithium salt of the corresponding ligand. Distorted trigonal prismatic and octahedral coordination geometries as well as C(1)-symmetric structures are found for zirconium complexes and in the solid state. Variable temperature (1)H NMR spectra indicated the fluxional nature of and in solution. Upon activation with methylaluminoxane (MAO), all these complexes except hafnium complex displayed moderate catalytic activities for ethylene polymerization. 1,2-Ethanediyl-linked complexes and are generally more active than their 1,3-propanediyl-linked analogues. The substituents at the ortho-positions of the phenyl rings have different effect on the catalytic activities of 1,2-ethanediyl-linked series or 1,3-propanediyl-linked series. It is noteworthy that even at a low Al/Zr molar ratio of 500, the catalytic activities of these zirconium complexes could be retained. Polyethylenes with broad molecular weight distributions (MWD = 15.3-20.3) were produced, which might result from the fluxional character of the zirconium complexes. The linear structure of obtained polyethylenes was further determined by (13)C NMR spectroscopy and DSC analysis.

Formal synthesis of the ACE inhibitor benazepril x HCl via an asymmetric aza-Michael reaction.

A formal enantioselective synthesis of benazepril.HCl (4), an anti- hypertensive drug, is reported. Our synthesis employed an asymmetric aza-Michael addition of L-homophenylalanine ethyl ester (LHPE, 1) to 4-(2-nitrophenyl)-4-oxo- but-2-enoic acid methyl ester (6) as the key step to prepare (2S,3'S)-2-(2-oxo-2,3,4,5- tetrahydro-1H-benzo[b]azepin-3-ylamino)-4-phenylbutyric acid ethyl ester (8), which is the key intermediate leading to benazepril x HCl (4).

Ethylene trimerization with a half-sandwich titanium complex bearing a pendant thienyl group.

A half-sandwich titanium complex with a pendant thienyl group, activated by methylalumoxane (MAO), can trimerize ethylene to 1-hexene with considerable activity and high selectivity; the coodination of the sulfur atom to the titanium center is proposed to be responsible for the selective trimerization of ethylene.

A highly efficient catalytic system for cross-coupling of aryl chlorides and bromides with malononitrile anion by palladium carbene complexes.

Six imidazolium chlorides (1-6) as precursors of 1,3-diaryl substituted N-heterocyclic carbene ligands were synthesized and evaluated in palladium-catalyzed cross-coupling reactions of aryl chlorides and bromides with malononitrile in the presence of NaH. Among them, 1,3-bis(2,4,6-triethylphenyl)imidazolium chloride (5) and 1,3-bis(2,4,6-triisopropylphenyl)imidazolium chloride (6) are novel. The catalytic system combining Pd(0) with imidazolium salts 4, 5 and 6 with bulky aryl groups in pyridine is found to be superior over others and afforded alpha-arylmalononitriles in high yields when employing a wide variety of substrates.