Global dynamics of a parabolic type equation arising from the curvature flow

This paper studies a type of degenerate parabolic problem with nonlocal term \begin{equation*} \begin{cases} u_t=u^p(u_{xx}+u-\bar{u}) & 0<t<T_{{\max}},\ 0<x<a, u_x(0,t)=u_x(a,t)=0 & 0<t<T_{{\max}}, u(x,0)=u_0(x) & 0<x<a, \end{cases} \end{equation*} where $p>1$, $a>0$. In this paper, the classification of the finite-time blowup/global existence phenomena based on the associated energy functional and explicit expression of all nonnegative steady states are demonstrated. Moreover, we combine the applications of Lojasiewicz-Simon inequality and energy estimates to derive that any bounded solution with positive initial data converges to some steady state as $t\rightarrow +\infty$

Suppression of long non-coding RNA H19 inhibits proliferation, cell migration and invasion in human cervical cancer cells

Purpose: To determine the expression profile of lncRNA H19 in different cervical cancers, and to decipher its function in the growth and metastasis of cervical cancer.Methods: The analysis LncRNA H19 expression was performed using quantitative real timepolymerase chain reaction (qRT-PCR). Cell counting kit 8 (CCK8) assay was used to assess the viability of the cells. The cells were transfected with Si-H19 using Lipofectamine 2000 and the metastasis of cells was determined by cell migration and invasion assay. Immunoblotting was used to evaluate the protein expression.Results: The lncRNA H19 expression was considerably enhanced in cervical cancer cells, and was about 2.6 to 5.3 times more in cervical cancer cells relative to non-cancer cells. Inhibition of lncRNA caused significant reduction in cervical cancer cell growth in a time-dependent manner. In addition while silencing of lncRNA inhibited the metastasis of HeLa cells. Cell migration and invasion was about 26 % in Si-H19 transfected cervical cancer cells, relative to 65 % in Si-NC cervical HeLa cells. Similarly, cell invasion was 45 % in Si-H19 cervical HeLa cells relative to the negative control (Si-NC). Inhibition of HeLa cell metastasis was also concomitant with decline of metalloproteinases (MMP)-2 and 9expression.Conclusion: lncRNA regulates the growth and metastasis of cervical cancer cells. Thus, IncRNA may be an important therapeutic agent for cervical cancer.Keywords: Cervical cancer, lncRNA, Proliferation, Invasio

Abnormal brain spontaneous activity in major depressive disorder adolescents with non-suicidal self injury and its changes after sertraline therapy

BackgroundNon-suicidal self-injury (NSSI) commonly occurs among adolescents with major depressive disorder (MDD), causing adverse effects on the physical and mental health of the patients. However, the underlying neurobiological mechanism of NSSI in adolescents with MDD (nsMDDs) remains unclear, and there are still challenges in the treatment. Studies have suggested that sertraline administration could be an effective way for treatment.MethodsTo verify the effectiveness and to explore the neurobiological processes, we treated a group of adolescents with nsMDDs with sertraline in this study. The brain spontaneous activity alteration was then investigated in fifteen unmedicated first-episode adolescent nsMDDs versus twenty-two healthy controls through the resting-state functional magnetic resonance imaging. Besides the baseline scanning for all participants, the nsMDDs group was scanned again after eight weeks of sertraline therapy to examine the changes after treatment.ResultsAt pre-treatment, whole brain analysis of mean amplitude of low-frequency fluctuation (mALFF) was performed to examine the neuronal spontaneous activity alteration, and increased mALFF was found in the superior occipital extending to lingual gyrus in adolescent nsMDDs compared with controls. Meanwhile, decreased mALFF was found in the medial superior frontal in adolescent nsMDDs compared with controls. Compared with the pre-treatment, the nsMDDs group was found to have a trend of, respectively, decreased and increased functional neuronal activity at the two brain areas after treatment through the region of interest analysis. Further, whole brain comparison of mALFF at pre-treatment and post-treatment showed significantly decreased spontaneous activity in the orbital middle frontal and lingual gyrus in adolescent nsMDDs after treatment. Also, depression severity was significantly decreased after treatment.ConclusionThe abnormal functional neuronal activity found at frontal and occipital cortex implied cognitive and affective disturbances in adolescent nsMDDs. The trend of upregulation of frontal neuronal activity and downregulation of occipital neuronal activity after sertraline treatment indicated that the therapy could be effective in regulating the abnormality. Notably, the significantly decreased neuronal activity in the decision related orbital middle frontal and anxiety-depression related lingual gyrus could be suggestive of reduced NSSI in adolescent MDD after therapy

O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis

Protein synthesis is essential for cell growth, proliferation, and survival. Protein synthesis is a tightly regulated process that involves multiple mechanisms. Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer. Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively. Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G. In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation. In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA. Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation. The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis. Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins

Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK-Dependent Activation of the PI3K/AKT/mTOR Pathway

Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Ginsenoside Rg3, a type of traditional Chinese medicine extracted from ginseng, is widely used to cure many inflammation-related diseases. However, the specific molecular mechanism of the effects of ginsenoside Rg3 on inflammation has rarely been reported. Thus, we established a mouse model of lipopolysaccharide (LPS)-induced ALI to investigate the immune protective effects of ginsenoside Rg3 and explore its molecular mechanism. In wild type (WT) mice, we found that ginsenoside Rg3 treatment significantly mitigated pathological damages and reduced myeloperoxidase (MPO) activity as well as the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6); furthermore, the production of anti-inflammatory mediators interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), polarization of M2 macrophages and expression levels of the phosphorylation of phosphatidylinositol 3-hydroxy kinase (PI3K), protein kinase B (PKB, also known as AKT), mammalian target of rapamycin (mTOR) and Mer receptor tyrosine kinase (MerTK) were promoted. However, there were no significant differences with regards to the pathological damage, MPO levels, inflammatory cytokine levels, and protein expression levels of the phosphorylation of PI3K, AKT and mTOR between the LPS treatment group and ginsenoside Rg3 group in MerTK-/- mice. Taken together, the present study demonstrated that ginsenoside Rg3 could attenuate LPS-induced ALI by decreasing the levels of pro-inflammatory mediators and increasing the production of anti-inflammatory cytokines. These processes were mediated through MerTK-dependent activation of its downstream the PI3K/AKT/mTOR pathway. These findings identified a new site of the specific anti-inflammatory mechanism of ginsenoside Rg3

Next-Generation Sequencing in Early Diagnosis of Dent Disease 1: Two Case Reports

Dent disease 1 is a rare X-linked recessive inherited disease, caused by pathogenic variants in the chloride voltage-gated channel 5 (CLCN5) gene. Dent disease 1 is characterized by low molecular weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, and chronic kidney disease. Infants may manifest only asymptomatic LMW proteinuria, which increases the difficulty of early diagnosis. We describe two male infants presenting only with nephrotic-range LMW proteinuria observed on examination using urine protein electrophoresis. Hereditary renal tubular diseases were highly suspected based on early onset age and LMW proteinuria. Thus, next-generation sequencing (NGS) was performed and pathogenic mutations in CLCN5 were identified in both patients. A diagnosis of Dent disease 1 was established based on the above informations. The two patients developed hypercalciuria during late follow-up, which verified the diagnosis. These two cases highlight the importance of next-generation sequencing in the early diagnosis of Dent disease 1 with only LMW proteinuria

A Simple and Sensitive Method for Measuring Tumor-Specific T Cell Cytotoxicity

A simple and sensitive method to quantitatively measure the cytolytic effect of tumor-specific T killer cells is highly desirable for basic and clinical studies. Chromium (51Cr) release assay has been the “gold standard” for quantifying cytolytic activities of cytotoxic T lymphocytes (CTLs) against target cells and this method is still being used in many laboratories. However, a major drawback of this method is the use of radioactive materials, which is inconvenient to handle because of environmental safety concerns and expensive due to the short half-life of the isotope. Consequently, several nonradioactive methods have been reported recently. Here we report a new method that we recently developed for quantifying antigen-specific cytolytic activity of CTLs. This method fully exploits the high sensitivity and the relative simplicity of luciferase quantitative assay. We initially expected the released luciferase in the supernatant to be the adequate source for monitoring cell death. However, to our total surprise, incubation of these killer T cells with the tumor cell targets did not result in significant release of luciferase in the culture medium. Instead, we found that the remaining luciferase inside the cells could accurately reflect the overall cell viability

Optical Transmission Through Multilayered Ultra-Thin Metal Gratings

Natural Science Foundation of Fujian Province of China [2011J06002]; program for NCET in China [08-0469]Optical transmission properties of multilayered ultra-thin metal gratings are numerically studied. The transmission spectrum has a broad stop-band with extremely low transmittance compared to that of a single-layer one for TM polarization. The stop-band is shown to be formed by multiple-interference tunneling and various plasmon resonance processes in ultra-thin-metal and dielectric multilayers. That is on the transmission background of non-apertured metal/dielectric multilayer structures that have low transmission in the long-wavelength range due to destructive multiple-interference tunneling, the transmission is further suppressed in the stop-band by plasmon resonances in the top metal/dielectric layers, e. g., the anti-symmetric bound surface plasmon mode in the ultra-thin metal layer and the gap surface plasmon mode in the metal-sandwiched dielectric layer. High transmission beyond the stop-band is due to coupled gap surface plasmon mode in the entire multilayer structures. Applications of the optical properties of the multilayered ultra-thin metal gratings are suggested for optical filtering (wavelength or polarization selective)