The degree threshold for covering with all the connected 33-graphs with 33 edges

Given two $r$-uniform hypergraphs $F$ and $H$, we say that $H$ has an $F$-covering if every vertex in $H$ is contained in a copy of $F$. Let $c_{i}(n,F)$ be the least integer such that every $n$-vertex $r$-graph $H$ with $\delta_{i}(H)>c_i(n,F)$ has an $F$-covering. Falgas-Ravry, Markst\"om and Zhao (Combin. Probab. Comput., 2021) asymptotically determined $c_1(n,K_{4}^{(3)-})$, where $K_{4}^{(3)-}$ is obtained by deleting an edge from the complete $3$-graph on $4$ vertices. Later, Tang, Ma and Hou (arXiv, 2022) asymptotically determined $c_1(n,C_{6}^{(3)})$, where $C_{6}^{(3)}$ is the linear triangle, i.e. $C_{6}^{(3)}=([6],\{123,345,561\})$. In this paper, we determine $c_1(n,F_5)$ asymptotically, where $F_5$ is the generalized triangle, i.e. $F_5=([5],\{123,124,345\})$. We also determine the exact values of $c_1(n,F)$, where $F$ is any connected $3$-graphs with $3$ edges and $F\notin\{K_4^{(3)-}, C_{6}^{(3)}, F_5\}$.Comment: 17 pages, 10 figure

Efficacy of nucleoside analogues on hepatitis B virus-related liver failure: A network meta-analysis

The purpose of this study was to compare the efficacy of nucleoside analogues (NAs) in the treatment of HBV-related liver failure. The data of patients with HBV-related liver failure treated with nucleoside analogues were used to conduct a network meta-analysis. A total of 1660 patients from 12 articles about the efficacy of lamivudine, entecavir, telbivudine and tenofovir for HBV-related liver failure treatment were recruited in the study. The highest two- and three-month survival rate was recorded for patients using tenofovir. The end-stage liver disease (MELD) score and mortality in patients undergoing tenofovir treatment were the lowest. Patients treated with telbivudine had the highest one-month survival rate. Patients receiving enticavir therapy showed the lowest HBV DNA level. Our results indicate that tenofovir may be the best therapy for the treatment of HBV-related liver failure compared to other nucleoside analogues (including lamivudine, entecavir and telbivudine) and non-NAs treatment

PAMELA data and leptonically decaying dark matter

Recently PAMELA released their first results on the positron and antiproton ratios. Stimulated by the new data, we studied the cosmic ray propagation models and calculated the secondary positron and antiproton spectra. The low energy positron ratio can be consistent with data in the convection propagation model. Above $\sim 10$ GeV PAMELA data shows a clear excess on the positron ratio. However, the secondary antiproton is roughly consistent with data. The positron excess may be a direct evidence of dark matter annihilation or decay. We compare the positron and anti-proton spectra with data by assuming dark matter annihilates or decays into different final states. The PAMELA data actually excludes quark pairs being the main final states, disfavors gauge boson final states. Only in the case of leptonic final states the positron and anti-proton spectra can be explained simultaneously. We also compare the decaying and annihilating dark matter scenarios to account for the PAMELA results and prefer to the decaying dark matter. Finally we consider a decaying neutralino dark matter model in the frame of supersymmetry with R-parity violation. The PAMELA data is well fitted with neutralino mass $600\sim 2000$ GeV and life time $\sim 10^{26}$ seconds. We also demonstrate that neutralino with mass around 2TeV can fit PAMELA and ATIC data simultaneously.Comment: 24 pages, 7 figures, 4 tables. v2: The new version includes the ATIC result which shows that decaying dark matter can interpret PAMELA and ATIC simultaneously; more references adde

Palbociclib Treatment Alters Nucleotide Biosynthesis and Glutamine Dependency in A549 Cells

Background Aberrant activity of cell cycle proteins is one of the key somatic events in non-small cell lung cancer (NSCLC) pathogenesis. In most NSCLC cases, the retinoblastoma protein tumor suppressor (RB) becomes inactivated via constitutive phosphorylation by cyclin dependent kinase (CDK) 4/6, leading to uncontrolled cell proliferation. Palbociclib, a small molecule inhibitor of CDK4/6, has shown anti-tumor activity in vitro and in vivo, with recent studies demonstrating a functional role for palbociclib in reprogramming cellular metabolism. While palbociclib has shown efficacy in preclinical models of NSCLC, the metabolic consequences of CDK4/6 inhibition in this context are largely unknown. Methods In our study, we used a combination of stable isotope resolved metabolomics using [U-13C]-glucose and multiple in vitro metabolic assays, to interrogate the metabolic perturbations induced by palbociclib in A549 lung adenocarcinoma cells. Specifically, we assessed changes in glycolytic activity, the pentose phosphate pathway (PPP), and glutamine utilization. We performed these studies following palbociclib treatment with simultaneous silencing of RB1 to define the pRB-dependent changes in metabolism. Results Our studies revealed palbociclib does not affect glycolytic activity in A549 cells but decreases glucose metabolism through the PPP. This is in part via reducing activity of glucose 6-phosphate dehydrogenase, the rate limiting enzyme in the PPP. Additionally, palbociclib enhances glutaminolysis to maintain mitochondrial respiration and sensitizes A549 cells to the glutaminase inhibitor, CB-839. Notably, the effects of palbociclib on both the PPP and glutamine utilization occur in an RB-dependent manner. Conclusions Together, our data define the metabolic impact of palbociclib treatment in A549 cells and may support the targeting CDK4/6 inhibition in combination with glutaminase inhibitors in NSCLC patients with RB-proficient tumors

Saikosaponin A Alleviates Symptoms of Attention Deficit Hyperactivity Disorder through Downregulation of DAT and Enhancing BDNF Expression in Spontaneous Hypertensive Rats

The disturbed dopamine availability and brain-derived neurotrophic factor (BDNF) expression are due in part to be associated with attention deficit hyperactivity disorder (ADHD). In this study, we investigated the therapeutical effect of saikosaponin a (SSa) isolated from Bupleurum Chinese DC, against spontaneously hypertensive rat (SHR) model of ADHD. Methylphenidate and SSa were orally administered for 3 weeks. Activity was assessed by open-field test and Morris water maze test. Dopamine (DA) and BDNF were determined in specific brain regions. The mRNA or protein expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicles monoamine transporter (VMAT) was also studied. Both MPH and SSa reduced hyperactivity and improved the spatial learning memory deficit in SHRs. An increased DA concentration in the prefrontal cortex (PFC) and striatum was also observed after treating with the SSa. The increased DA concentration may partially be attributed to the decreased mRNA and protein expression of DAT in PFC while SSa exhibited no significant effects on the mRNA expression of TH and VMAT in PFC of SHRs. In addition, BDNF expression in SHRs was also increased after treating with SSa or MPH. The obtained result suggested that SSa may be a potential drug for treating ADHD

The IRE1α-XBP1 Pathway of the Unfolded Protein Response Is Required for Adipogenesis

SummarySignaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARγ and C/EBPα. Here we demonstrate that the IRE1α-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryonic fibroblasts and 3T3-L1 cells with XBP1 or IRE1α knockdown exhibit profound defects in adipogenesis. Intriguingly, C/EBPβ, a key early adipogenic factor, induces Xbp1 expression by directly binding to its proximal promoter region. Subsequently, XBP1 binds to the promoter of Cebpa and activates its gene expression. The posttranscriptional splicing of Xbp1 mRNA by IRE1α is required as only the spliced form of XBP1 (XBP1s) rescues the adipogenic defect exhibited by XBP1-deficient cells. Taken together, our data show that the IRE1α-XBP1 pathway plays a key role in adipocyte differentiation by acting as a critical regulator of the morphological and functional transformations during adipogenesis