Method of determining cosmological parameter ranges with samples of candles with an intrinsic distribution

In this paper, the effect of the intrinsic distribution of cosmological candles is investigated. We find that, in the case of a narrow distribution, the deviation of the observed modulus of sources from the expected central value could be estimated within a ceratin range. We thus introduce a lower and upper limits of $\chi ^{2}$, $\chi_{\min}^{2}$ and $\chi_{\max}^{2}$, to estimate cosmological parameters by applying the conventional minimizing $\chi ^{2}$ method. We apply this method to a gamma-ray burst (GRB) sample as well as to a combined sample including this GRB sample and an SN Ia sample. Our analysis shows that: a) in the case of assuming an intrinsic distribution of candles of the GRB sample, the effect of the distribution is obvious and should not be neglected; b) taking into account this effect would lead to a poorer constraint of the cosmological parameter ranges. The analysis suggests that in the attempt of constraining the cosmological model with current GRB samples, the results tend to be worse than what previously thought if the mentioned intrinsic distribution does exist.Comment: 6 pages,4 figures,1 tables.Data updated. Main conclusion unchange

INTERVENTION EFFECT AND DOSE-DEPENDENT RESPONSE OF TANREQING INJECTION ON AIRWAY MUCUS HYPERSECRETION IN LIPOPOLYSACCHARIDE-INDUCED RATS

Background: Tanreqing injection, a Chinese herbal formulation comprising Radix Scutellariae, Fructus Forsythiae, Flos Lonicerae, Antelope horn, and Bear bile powder, has been used to treat bronchitis and pneumonia for many years in China. However, its anti-mucus-hypersecretion mechanism has yet not been fully interpreted. We aim to assess the effect and dose-response relationships of Tanreqing injection on lipopolysacchaide (LPS) induced airway mucus hypersecretion in rats. Material and methods: Forty-eight male rats were randomly divided into four groups (12 per group). A rat model of airway mucus hypersecretion was generated with LPS. Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total protein was determined by bicinchoninic acid disodium assay (BCA). Muc5ac was measured using enzyme linked immunosorbent assay (ELISA) and immunohistochemistry. The expression of muc5ac mRNA was detected by real-time polyermase chain reaction (RT-PCR). The middle lobe of the right lung was stained with alcian blue-periodic acid sthiff (AB-PAS) and positive staining relative shading area examined. Results: LPS caused airway mucus hypersecretion, The LPS-induced airway mucus hypersecretion increased beginning at 24 hr, and peaked at 96 hr. Tanreqing injection could inhibit airway mucus hypersecretion, and suppress the expression of muc5ac mRNA. Conclusion: Tanreqing injection inhibits airway mucus hypersecretion in a certain dose-dependent trend

Effect of estradiol on proliferation and differentiation of side population stem/progenitor cells from murine endometrium

<p>Abstract</p> <p>Background</p> <p>In our previous study, endometrium side population cells (SP cells) were isolated from postpartum murine uterus, and characterized by a heterogeneous population of stem/progenitor cells. In this study, we investigated the effect of estrogen on the proliferation and differentiation of SP cells.</p> <p>Methods</p> <p>SP and non-SP cells of postpartum murine endometrium were isolated by DNA dye Hoechst 33342. The expression of estrogen receptor 1 (ESR1) was measured by reverse transcription polymerase chain reaction (RT-PCR), Real-time PCR, Western blot, immunofluorescence and immunohistochemistry. The proliferation and differentiation of SP cells treated with different concentrations [10(-8) M-10(-6) M] of estradiol (E2) and E2+ ICI182780 (Faslodex, inhibitor of ESR1) were measured by 3-(4, 5-dimethylthiazoly1-2)-2,5-diphenyltetrazolium bromide(MTT) and clonogenic assays.</p> <p>Results</p> <p>(1) SP cells expressed ESR1 at a higher level than non-SP cells. (2) The level of E2 in the serum and the expression of ESR1 in the uterus of postpartum murine changed in the same manner with the ratio of SP cells to total uterus cells at a different postpartum time point. ESR1, as ABCG2 is also predominantly located in the stroma and the glandular epithelium of the uterus. (3) 10(-6) M E2 notably promoted the proliferation of SP cells after treatment for 24 h. This effect could be inhibited by ICI182780. E2 at the concentration of 10(-7) M or 10(-8) M was sent to impair the large cloning efficiency (CE) of SP cells.</p> <p>Conclusions</p> <p>The effect of estrogen on the proliferation and differentiation of endometrium SP cells via ESR1 was observed and it was in a concentration dependent fashion. Clearly, more work is needed to understand the <it>in vivo </it>effect of E2 at the physiological concentration on the differentiation of SP cells.</p

Genome Editing of Pik3cd Impedes Abnormal Retinal Angiogenesis

Abnormal angiogenesis is associated with myriad human diseases including proliferative diabetic retinopathy. Signaling transduction via phosphoinositide 3-kinases (PI3Ks) plays a critical role in angiogenesis. Herein, we showed that p110δ, the catalytic subunit of PI3Kδ, was highly expressed in pathological retinal vascular endothelial cells (ECs) in a mouse model of oxygen-induced retinopathy (OIR) and in fibrovascular membranes from patients with proliferative diabetic retinopathy. To explore novel intervention with PI3Kδ expression, we developed a recombinant dual adeno-associated viral (rAAV) system for delivering CRISPR/Cas9 in which Streptococcus pyogenes (Sp) Cas9 expression was driven by an endothelial specific promoter of intercellular adhesion molecule 2 (pICAM2) to edit genomic Pik3cd, the gene encoding p110δ. We then demonstrated that infection of cultured mouse vascular endothelial cells with the dual rAAV1s of rAAV1-pICAM2-SpCas9 and rAAV1-SpGuide targeting genomic Pik3cd resulted in 80% DNA insertion/deletion in the locus of genomic Pik3cd and 70% depletion of p110δ expression. Furthermore, we showed that in the mouse model of OIR editing retinal Pik3cd with the dual rAAV1s resulted in not only a significant decrease in p110δ expression, and Akt activation, but also a dramatic reduction in pathological retinal angiogenesis. These findings reveal that Pik3cd editing is a novel approach to treating abnormal retinal angiogenesis

Correction to: Genome Editing of Pik3cd Impedes Abnormal Retinal Angiogenesis, by Wu et al. Hum Gene Ther 2023;34(1-2):30-41; doi: 10.1089/hum.2022.079

In the January 2023 issue of Human Gene Therapy (vol. 34, no. 1-2; 30–41), the article titled Genome Editing of Pik3cd Impedes Abnormal Retinal Angiogenesis, by Wu et al. requires correction. The author byline originally appeared with the 13th author's name incorrectly published as GuomingZhao Wenyi Wu,1,2,3 Gaoen Ma,4 Hui Qi,5 Lijun Dong,5 Fang Chen,6 Yun Wang,5 Xingxing Mao,5 Xiaoqing Guo,2,3 Jing Cui,7 Joanne Aiko Matsubara,7 Bart Vanhaesebroeck,8 Xiaohe Yan,5Guoming Zhao,5 Shaochong Zhang,5,* and Hetian Lei 5,* The correct spelling of the author's name is GuomingZhang The online version of the article has been corrected to reflect this. The authors apologize for the error

Highly hydrated paramagnetic amorphous calcium carbonate nanoclusters as a superior MRI contrast agent

Amorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T1 weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent

Recent advances in the study of anesthesia-and analgesia-related mechanisms of S-ketamine

Ketamine is a racemic mixture of equal amounts of R-ketamine and S-ketamine and is well known to anesthesiologists for its unique dissociative anesthetic properties. The pharmacological properties of ketamine, namely, its sympathetic excitation, mild respiratory depression, and potent analgesia, are still highly valued in its use as an anesthetic for some patients. In particular, since its advent, S-ketamine has been widely used as an anesthetic in many countries due to its increased affinity for NMDA receptors and its enhanced anesthetic and analgesic effects. However, the anesthetic and analgesic mechanisms of S-ketamine are not fully understood. In addition to antagonizing NMDA receptors, a variety of other receptors or channels may be involved, but there are no relevant mechanistic summaries in the literature. Therefore, the purpose of this paper is to review the mechanisms of action of S-ketamine on relevant receptors and systems in the body that result in its pharmacological properties, such as anesthesia and analgesia, with the aim of providing a reference for its clinical applications and research

Diosgenin Suppresses Cholangiocarcinoma Cells Via Inducing Cell Cycle Arrest And Mitochondria-Mediated Apoptosis.

Purpose(#br)Diosgenin (DSG) is the precursor of steroid hormones and plays a crucial part in the proliferation of various carcinomas including human colorectal cancer and gastric carcinoma. Nevertheless, its specific features and mechanisms in human cholangiocarcinoma (CCA) remain unknown.(#br)Methods(#br)MTS assay, colony-forming assay, and EdU assay were performed to determine the role of DSG on the progression of human CCA cells. The distributions of cell cycle, the ratio of apoptosis, and the mitochondrial membrane potential (ΔΨm) were studied by flow cytometry (FCM). AO/EB and Hoechst 33258 staining were performed to observe the morphological features of cell apoptosis. TEM was performed to observe the ultrastructures of QBC939 and HuCCT1 cells. The mRNA and protein expression of mitochondrial apoptotic pathway and GSK3β/β-catenin pathway were further confirmed by qPCR and Western blotting. The xenograft tumor model of HuCCT1 cells was built. Immunohistochemistry of tumor tissues was performed.(#br)Results(#br)Our results indicated that DSG inhibited the progression of six CCA cell lines. In vivo tumor studies also indicated that DSG significantly inhibited tumor growth in xenografts in nude mice. The expression of mitosis-promoting factor cyclinB1 was decreased along with the elevating level of cell cycle inhibitor p21, resulting in arresting CCA cell cycles at G2/M phase. Furthermore, DSG induced apoptosis with the increased expressions of cytosol cytochrome C, cleaved-caspase-3, cleaved-PARP1 and the Bax/Bcl-2 ratio. Mechanistically, our study showed that GSK3β/β-catenin pathway was involved in the apoptosis of CCA cells. Thus, DSG might provide a new clue for the drug therapy of CCA.(#br)Conclusion(#br)In our data, DSG was found to have efficient antitumor potential of human CCA cells in vitro and in vivo

A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure