The Chinese formula Tang-Min-Ling (TML), an improved product of the decoction of Dachaihu which has a history of more than 2000 years, has main constituents of Coptis chinensis Franch, Scutellaria ...baicalensis Georgi, Rheum officinale Baill and Bupleurum chinense DC. A multi-central randomized controlled investigation performed previously by us has showed that TML has positive effects on regulating glycometabolism in type 2 diabetes (T2DM) patients, but the mechanisms remain unclear. Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model with rosiglitazone as a positive control, we were able to detect TML's effect on the serum glucose, serum lipid, serum leptin and adiponcetin after oral administration for 12 weeks. We were also able to detect the insulin resistance level by a glucose clamp test and study the mechanisms of TML in improving insulin resistance by detecting skeletal muscle AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). Results showed that TML significantly reduced the glucose area under a curve of the oral glucose tolerance test, and had a positive effect in regulating serum lipid metabolism. TML treatment also significantly reduced the serum leptin level, but it had no effect on the serum adiponectin level. The AMPK enzymatic activity and GLUT4 expression in Skeletal Muscle were also upregulated in the TML group. The results suggest that the Chinese medicine TML, which contains Coptis chinensis Franch as one of its components, improves glycometabolism and its possible mechanisms may involve in improvement of insulin resistance of OLETF rats.
SrAl
2
O
4
:Eu
2+
, Dy
3+
has been widely studied as a classical persistent phosphor due to its stability and long green-afterglow duration. In this study, a series of Ce
3+
co-doped SrAl
2
O
4
:Eu
...2+
, Dy
3+
phosphors were prepared by the traditional solid state reaction method, sintering under Ar + 5% H
2
atmosphere in the temperature range of 1300–1500°C. The effect of Ce
3+
co-doping on luminescence performance of SrAl
2
O
4
:Eu
2+
, Dy
3+
was investigated at Ce
3+
concentration of 0–0.3 at %. Under excitation wavelengths of 365, 400 and 460 nm, respectively, the luminescence intensity was found to increase linearly with rise of sintering temperature or Ce
3+
doping concentrations. It was ascribed to the sufficient crystallization at high sintering temperature as well as the high absorption cross section of Ce
3+
ion. Besides, the Ce
3+
co-doping speeds up the afterglow time without introducing the emission wavelength shift. Therefore, Ce
3+
co-doped SrAl
2
O
4
: Eu, Dy is a promising high efficient phosphor for compensated the dark period in alternating current driven light-emitting diodes (AC-LED) lighting.
Two tri-n-butylphosphme-participated ( PBu3n) nickel (Ⅱ) complexes of 2-mercaptophenol(H2mp),i.e,Ni2Ru(mp)3(Hmp)(PBu3n)3 3 exhibiting a curved heterotrinuclear metal skeleton and its mononuclear ..."synthon",HNEt3 Ni(mp) (Hmp) (PBu3n) 1 were synthesized and characterized by X-crystallography and 1H NMR,FAB-MS and cyclic valtammogram measurements.The nickel(Ⅱ) center in 1 has a square-planar geometry For 3,the ruthenium(Ⅲ) atom is in a distorted octahedral environment and the two mckel(Ⅱ) atoms exhibit square-planar and rare triangle-planar geometries,respectively.The Ni (1)-Ru-Ni(2 ) arrangement is severely asymmetric with the distances 0.254 and 0.394 nm,respectively,for Ni(1)-Ru and Ni(2)-Ru.The structural regularities of relevant complexes are summarized in relation to the structural as well as spectra data.
A doubly Q-switched 1.06 μm pulsed laser using a novel tape casting YAG/Nd:YAG/YAG composite ceramic with a sandwich structure was demonstrated for the first time. Compared to purely acousto-optical ...(AO) Q-switching, this laser using an AO Q-switch and Cr
4+
:YAG saturable absorber simultaneously can generate shorter pulses. The pulsed laser performance was investigated at two modulated repetition rates of 10 and 20 kHz.
Acceptable faults in a circuit under test (CUT) refer to those faults that have no or only minor impacts on the performance of the CUT. A circuit with an acceptable fault may be marketable for some ...specific applications. Therefore, by carefully dealing with these faults during testing, significant yield improvement can be achieved. Previous studies have shown that the patterns generated by a conventional automatic test pattern generation procedure to detect all unacceptable faults also detect many acceptable ones, resulting in a severe loss on achievable yield improvement. In this paper, we present a novel test methodology called multiple test set detection (MTSD) to totally eliminate this overdetection problem. A basic test set generation method is first presented, which depicts a fundamental scheme to generate appropriate test sets for MTSD. We then describe an enhanced test generation method that can significantly reduce the total number of test patterns. Solid theoretical derivations are provided to validate the effectiveness of the proposed methods. Experimental results show that in general an 80%-99% reduction in the number of test patterns can be achieved compared with previous work addressing this problem.
R values measured with the BESII detector at center-of-mass energies between 3.7 and 5.0 GeV are fitted to determine resonance parameters (mass, total width, electron width) of the high mass ...charmonium states, ψ(3770), ψ(4040), ψ(4160) and ψ(4415). Various effects, including the interferences and relative phases between the resonances, the energy-dependence of the full widths, and the initial state radiative correction, are examined. The results are compared to previous studies.
Immunomodulatory drugs (IMiDs) have markedly improved patient outcome in multiple myeloma (MM); however, resistance to IMiDs commonly underlies relapse of disease. Here, we identify that tumor ...necrosis factor (TNF) receptor-associated factor 2 (
) knockdown (KD)/knockout (KO) in MM cells mediates IMiD resistance via activation of noncanonical nuclear factor κB (NF-κB) and extracellular signal-regulated kinase (ERK) signaling. Within MM bone marrow (BM) stromal cell supernatants, TNF-α induces proteasomal degradation of TRAF2, noncanonical NF-κB, and downstream ERK signaling in MM cells, whereas interleukin-6 directly triggers ERK activation. RNA sequencing of MM patient samples shows nearly universal ERK pathway activation at relapse on lenalidomide maintenance therapy, confirming its clinical relevance. Combination MEK inhibitor treatment restores IMiD sensitivity of
KO cells both in vitro and in vivo. Our studies provide the framework for clinical trials of MEK inhibitors to overcome IMiD resistance in the BM microenvironment and improve patient outcome in MM.
Purpose
Adjunct chemoradiation is offered to unresectable esophageal squamous cell carcinoma (ESCC) patients, while its use is limited in tumors with strong resistance. Oxygen carriers or ...anti-hypoxic drugs belong to an emerging class of regulators that can alleviate tumor hypoxia.
Methods
We investigate the potential use of a novel oxygen carrier YQ23 in sensitizing chemoresistant ESCC in a series of subcutaneous tumor xenograft models developed using ESCC cell lines with different strengths of chemosensitivities.
Results
Tumor xenografts were developed using SLMT-1 and HKESC-2 ESCC cell lines with different strengths of resistance to two chemotherapeutic drugs, 5-fluorouracil and cisplatin. More resistant SLMT-1 xenografts responded better to YQ23 treatment than HKESC-2, as reflected by the induced tumor oxygen level. YQ23 sensitized SLMT-1 xenografts toward 5-fluorouracil via its effect on reducing the level of a hypoxic marker HIF-1α. Furthermore, a derangement of tumor microvessel density and integrity was demonstrated with a concurrent decrease in the level of a tumor mesenchymal marker vimentin. Similar to the 5-fluorouracil sensitizing effect, YQ23 also enhanced the response of SLMT-1 xenografts toward cisplatin by reducing the tumor size and the number of animals with invasive tumors. Chemosensitive HKESC-2 xenografts were irresponsive to combined YQ23 and cisplatin treatment.
Conclusions
In all, YQ23 functions selectively on chemoresistant ESCC xenografts, which implicates its potential use as a chemosensitizing agent for ESCC patients.
Off-target binding or vector sequestration can significantly limit the efficiency of systemic virotherapy. We report here that systemically administered oncolytic measles virus (MV) was rapidly ...sequestered by the mononuclear phagocytic system (MPS) of the liver and spleen in measles receptor CD46-positive and CD46-negative mice. Since scavenger receptors on Kupffer cells are responsible for the elimination of blood-borne pathogens, we investigated here if MV uptake was mediated by scavenger receptors on Kupffer cells. Pretreatment of cells with poly(I), a scavenger receptor ligand, reduced MV expression by 99% in murine (J774A.1) macrophages and by 50% in human (THP-1) macrophages. Pre-dosing of mice with poly(I) reduced MPS sequestration of MV and increased circulating levels of MV by 4 to 15-folds at 2 min post virus administration. Circulating virus was still detectable 30 min post infusion in mice pre-dosed with poly(I) whereas no detectable MV was found at 5-10 min post infusion if mice did not receive poly(I). MPS blockade by poly(I) enhanced virus delivery to human ovarian SKOV3ip.1 and myeloma KAS6/1 xenografts in mice. Higher gene expression and improved control of tumor growth was noted early post therapy. Based on these results, incorporation of MPS blockade into MV treatment regimens is warranted.
Introduction X-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by Bruton's tyrosine kinase (Btk) gene mutation. Recent studies suggested genotype-phenotype correlation in ...XLA, but a definitive association remains controversial. Patients and Methods We examined the relationship between specific Btk gene mutations and severity of clinical presentation in 62 patients with XLA. Disease severity was assessed by the age of disease onset and the presence of severe infections, while mutations were classified into severe and mild based on structural and functional consequence by bioinformatics analysis. Results Fifty-six Btk mutations were identified in 62 patients from 57 kindreds. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset as well as occurrence of severe infections. Conclusion A critical analysis of the circumstances upon presentation also revealed that under-recognition of recurrent infections and relevant family history are important hurdles to timely diagnosis of XLA.
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