MiR-106b promotes cell proliferation via targeting RB in laryngeal carcinoma

MiR-106b is frequently up-regulated in various types of human cancer including laryngeal carcinoma. However the underlying mechanism of miR-106b involved in laryngeal carcinoma remains elusive. Here we showed that reduction of miR-106b induced cell cycle G0/G1 arrest by targeting tumor suppressor RB in human laryngeal carcinoma cells. Further, Introducing RB cDNA without 3'UTR abrogated miR-106b-induced cell proliferation. Finally, there was an inverse relationship between RB and miR-106b expression in laryngeal carcinoma tissues. To our knowledge, these data indicate for the first time that miR-106b directly regulate cell cycle by targeting RB in laryngeal carcinoma and that miR-106b could be potential therapeutic approaches for laryngeal carcinoma

A simulation study of support break-off and water inrush during mining under the high confined and thick unconsolidated aquifer

The thick Cenozoic unconsolidated aquifer is deposited under Sunan syncline core in Huaibei coalfield, the water yield property of unconsolidated bottom aquifer is strong and water pressure is high in some areas (up to 4 MPa in some areas). Water inrush accident often occurs during mining under unconsolidated aquifer, the biggest characteristic is abnormal mine pressure and support break-off during water inrush accident comparing with normal condition. In order to study mechanism of support break-off and water inrush during mining under the high confined thick unconsolidated aquifer, a simulation of similar material was designed. The experimental results indicated that, under normal condition, the compound breakage sequence of water-resisting key strata between coal seam and high confined thick unconsolidated aquifer is from top to bottom and the basic reason of synchronous fracture is the load of bottom key strata increased suddenly when the breakage of top key strata happened. Because of high confined thick unconsolidated aquifer, surface acts on the bottom key strata soil layer in the form of uniformly distributed load, which is the load-transfer mechanism of confined thick unconsolidated aquifer. Once the overlying key strata compound breaks, the height of unstable strata will reach far more than 30 meters and exceed support capability of current fully-mechanized mining supporter, which leads to support break-off accident during mining process under confined unconsolidated aquifer

Rural financial development, spatial spillover, and poverty reduction: evidence from China

Rural financial development is deemed essential for eliminating poverty. In China, successive governments have initiated a series of financial development plans to reduce poverty since the launch of economic reform in the late 1970s. However, there is a rising concern about whether financial development can reduce poverty in China. This study uses a panel dataset of 30 provinces (out of 31) in mainland China from 1997 to 2015 to examine the effect of rural financial development on poverty reduction. We employ a spatial panel model to investigate whether rural financial development has a positive spatial spillover effect. Moreover, we use the instrumental variable method to address the possible bidirectional causal effect between rural financial development and poverty reduction. Our study confirms that rural financial development does reduce poverty and simultaneously widen the urban-rural income gap. We further find that rural financial development has a positive spatial spillover effect on poverty alleviation and that the conventional panel model (e.g., fixed effects method) may underestimate the effect of rural financial development, as it ignores the spatial spillover effect

Novobiocin, a Newly Found TRPV1 Inhibitor, Attenuates the Expression of TRPV1 in Rat Intestine and Intestinal Epithelial Cell Line IEC-6

Background and Purpose: Novobiocin (NOVO), an ABC transporter inhibitor, decreases intestinal wall permeability of capsaicin (CAP), an ABC transporter substrate. However, the mechanism of this effect is not consistent with the action of NOVO as an ABC transporter inhibitor. We previously found that CAP can also be transported via TRPV1, which was site-specific in the permeability of CAP across the intestine. We explored the regulation by NOVO of TRPV1 in the present study.Methods: Rats and transfected IEC-6 cells were used as the models to assess intestinal permeability and expression of TRPV1. Ussing chamber and intracellular accumulation were used to evaluate the influence of NOVO on the transport of CAP in vitro. The expression of TRPV1 was detected after administration of NOVO by qRT-PCR, western blot and immunofluorescent imaging. In addition, MTT and lactate dehydrogenase (LDH) were used to evaluate the cytotoxicity of NOVO in both rat and cell models. Finally, the effect of NOVO on the absorption of CAP in vivo was studied by LC-MS/MS.Results:In vitro data showed that there existed a dose-dependent relationship in the range of concentration between 5 and 50 μM, and even 5 μM NOVO could decrease intestinal permeability of CAP across the intestine. Meanwhile, cytosolic accumulation of CAP decreased when NOVO was used simultaneously or 24 h in advance. NOVO exhibited an inhibition level similar to that of ruthenium red (RR) or SB-705498, a TRPV1-specific inhibitor. NOVO down-regulated TRPV1 expression in the intestine and in transfected cells in a concentration-dependent fashion, hinting that its inhibition of the permeability of CAP is due to its inhibition of TRPV1 expression. Immunofluorescent imaging data showed that the fluorescence intensity of TRPV1 was reduced after pre-treatment with NOVO and SB-705498. In vivo data further demonstrated that oral co-administration of NOVO decreased Cmax and AUC of CAP in dosage-dependent ways, consistent with its role as a TRPV1 inhibitor.Conclusion: NOVO could be a potential TRPV1 inhibitor by attenuating the expression of TRPV1 and may be used to attenuate permeability of TRPV1 substrates

The influence of high worry on static and dynamic insular functional connectivity

Worry is a form of repetitive negative thought. High worry-proneness is one risk factor leading to anxiety disorder. Several types of research indicated that anxiety disorder was highly associated with disrupted interoception. The insula is consistently considered to play a key role in interoception. However, the relationship between worry and the interoception network is poorly investigated in worry-prone individuals. Thus, it is essential to identify the neural characteristic of high worry-proneness subjects. A total of 32 high worry-proneness (HWP) subjects and 25 low worry-proneness (LWP) subjects were recruited and underwent magnetic resonance imaging scanning. Six subregions of insula were chosen as regions of interest. Then, seed-based static and dynamic functional connectivity were calculated. Increased static functional connectivity was observed between the ventral anterior insula and inferior parietal lobule in HWP compared to LWP. Decreased static functional connectivity was found between the left ventral anterior insula and the pregenual anterior cingulate cortex. Decreased dynamic functional connectivity was also shown between the right posterior insula and the inferior parietal lobule in HWP. Moreover, a post-hoc test exploring the effect of changed function within the insular region confirmed that a significant positive relationship between static functional connectivity (ventral anterior insula–inferior parietal lobule) and dynamic functional connectivity (posterior insula–inferior parietal lobule) in LWP but not in HWP. Our results might suggest that deficient insular function may be an essential factor related to high worry in healthy subjects

Characteristics of tumor infiltrating lymphocyte and circulating lymphocyte repertoires in pancreatic cancer by the sequencing of T cell receptors

Pancreatic cancer has a poor prognosis and few effective treatments. The failure of treatment is partially due to the high heterogeneity of cancer cells within the tumor. T cells target and kill cancer cells by the specific recognition of cancer-associated antigens. In this study, T cells from primary tumor and blood of sixteen patients with pancreatic cancer were characterized by deep sequencing. T cells from blood of another eight healthy volunteers were also studied as controls. By analyzing the complementary determining region 3 (CDR3) gene sequence, we found no significant differences in the T cell receptor (TCR) repertoires between patients and healthy controls. Types and length of CDR3 were similar among groups. However, two clusters of patients were identified according to the degree of CDR3 overlap within tumor sample group. In addition, clonotypes with low frequencies were found in significantly higher numbers in primary pancreatic tumors compared to blood samples from patients and healthy controls. This study is the first to characterize the TCR repertoires of pancreatic cancers in both primary tumors and matched blood samples. The results imply that specific types of pancreatic cancer share potentially important immunological characteristics

A rapid and ultra-sensitive dual readout platform for Klebsiella pneumoniae detection based on RPA-CRISPR/Cas12a

The bacterium Klebsiella pneumoniae (Kp) was the primary pathogen of hospital-acquired infection, but the current detection method could not rapidly and conveniently identify Kp. Recombinase polymerase amplification (RPA) was a fast and convenient isothermal amplification technology, and the clustered regularly interspaced short palindromic repeats (CRISPR) system could rapidly amplify the signal of RPA and improve its limit of detection (LOD). In this study, we designed three pairs of RPA primers for the rcsA gene of Kp, amplified the RPA signal through single-strand DNA reporter cleavage by CRISPR/Cas12a, and finally analyzed the cleavage signal using fluorescence detection (FD) and lateral flow test strips (LFTS). Our results indicated that the RPA-CRISPR/Cas12a platform could specifically identify Kp from eleven common clinical pathogens. The LOD of FD and LFTS were 1 fg/μL and 10 fg/μL, respectively. In clinical sample testing, the RPA-CRISPR/Cas12a platform was consistent with the culture method and qPCR method, and its sensitivity and specificity were 100% (16/16) and 100% (9/9), respectively. With the advantages of detection speed, simplicity, and accuracy, the RPA-CRISPR/Cas12a platform was expected to be a convenient tool for the early clinical detection of Kp