Since an outbreak of vaping-related deaths in the US has been reported as a public health crisis, the cardiovascular safety of nicotine nowadays receives increasing attention due to use of tobacco cigarette alternatives, such as electronic cigarettes. However, whether and how nicotine contributes to cardiac detrimental effects are in great controversy, especially less understood in young adult population. We report that chronic nicotine exposure, a major component of Electronic cigarettes, resulted in directly inhibited cardiomyocytes viability, increased cardiac fibrosis, and markedly suppressed cardiac function compared with sham. Gene array combined with bioinformatics analysis identified cardiac apoptosis and mitophagy were the key signals responsible for nicotine induced cardiac detrimental effect. Mechanistically, nicotine exposure markedly increased cleaved Caspase 3 and cleaved Caspase 9 indicating the involvement of intrinsic apoptotic pathway (mitochondrial cell death pathway). Meanwhile, nicotine-induced ROS outbreak promoted lysomal alkalization, furthermore blocked mitophagic degradation, thereby disrupted mitophagic flux promoted mitochondrial cell death cascade. Taken together, these findings indicate that nicotine confers cardiotoxicity via ROS-induced mitophagic flux blockage and provide the first demonstration of a causative link between nicotine and cardiac toxicity in young adult rat which may suggest nicotine induces cardiomyocytes impairment leading to cardiotoxicity in young adult population.

The interferon-regulated antiviral responses are essential for the induction of both innate and adaptive immunity in mammals. Production of virus-derived small-interfering RNAs (vsiRNAs) to restrict virus infection by RNA interference (RNAi) is a recently identified mammalian immune response to several RNA viruses, which cause important human diseases such as influenza and Zika virus. However, little is known about Dicer processing of viral double-stranded RNA replicative intermediates (dsRNA-vRIs) in mammalian somatic cells. Here we show that infected somatic cells produced more influenza vsiRNAs than cellular microRNAs when both were produced by human Dicer expressed de novo, indicating that dsRNA-vRIs are not poor Dicer substrates as previously proposed according to in vitro Dicer processing of synthetic long dsRNA. We report the first evidence both for canonical vsiRNA production during wild-type Nodamura virus infection and direct vsiRNA sequestration by its RNAi suppressor protein B2 in two strains of suckling mice. Moreover, Sindbis virus (SINV) accumulation in vivo was decreased by prior production of SINV-targeting vsiRNAs triggered by infection and increased by heterologous expression of B2 in cis from SINV genome, indicating an antiviral function for the induced RNAi response. These findings reveal that unlike artificial long dsRNA, dsRNA-vRIs made during authentic infection of mature somatic cells are efficiently processed by Dicer into vsiRNAs to direct antiviral RNAi. Interestingly, Dicer processing of dsRNA-vRIs into vsiRNAs was inhibited by LGP2 (laboratory of genetics and physiology 2), which was encoded by an interferon-stimulated gene (ISG) shown recently to inhibit Dicer processing of artificial long dsRNA in cell culture. Our work thus further suggests negative modulation of antiviral RNAi by a known ISG from the interferon response.

Since December 2019, an unexplained pneumonia has broken out in Wuhan, Hubei Province, China. In order to prevent the rapid spread of this disease, quarantine or lockdown measures were taken by the Chinese government. These measures turned out to be effective in containing the contagious disease. In spite of that, social distancing measures, together with disease itself, would potentially cause certain health risks among the affected population, such as sleep disorder. We herein conducted this web search analysis so as to examine the temporal and spatial changes of public search volume of the mental health topic of "insomnia" during COVID-19 pandemic in China.

Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 μM CTS and 200 μM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs' synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy.

The effect of robotic surgery (RS) for rectal cancer after neoadjuvant therapy is still controversial, and a comprehensive search and analysis of the current relevant evidence is necessary. Our study aimed to evaluate the efficacy of RS for rectal cancer after neoadjuvant therapy compared with conventional laparoscopic surgery (LS).

Ammonia toxicity is clinically important and biologically poorly understood. We reported previously that 3mM ammonia chloride (ammonia), a relevant concentration for hepatic encephalopathy studies, increases production of endogenous ouabain and activity of Na,K-ATPase in astrocytes. In addition, ammonia-induced upregulation of gene expression of α2 isoform of Na,K-ATPase in astrocytes could be inhibited by AG1478, an inhibitor of the EGF receptor (EGFR), and by PP1, an inhibitor of Src, but not by GM6001, an inhibitor of metalloproteinase and shedding of growth factor, suggesting the involvement of endogenous ouabain-induced EGF receptor transactivation. In the present cell culture study, we investigated ammonia effects on phosphorylation of EGF receptor and its intracellular signal pathway towards MAPK/ERK1/2 and PI3K/AKT; interaction between EGF receptor, α1, and α2 isoforms of Na,K-ATPase, Src, ERK1/2, AKT and caveolin-1; and relevance of these signal pathways for ammonia-induced cell swelling, leading to brain edema, an often fatal complication of ammonia toxicity. We found that (i) ammonia increases EGF receptor phosphorylation at EGFR(845) and EGFR(1068); (ii) ammonia-induced ERK1/2 and AKT phosphorylation depends on the activity of EGF receptor and Src, but not on metalloproteinase; (iii) AKT phosphorylation occurs upstream of ERK1/2 phosphorylation; (iv) ammonia stimulates association between the α1 Na,K-ATPase isoform, Src, EGF receptor, ERK1/2, AKT and caveolin-1; (v) ammonia-induced ROS production might occur later than EGFR transactivation; (vi) both ammonia induced ERK phosphorylation and ROS production can be abolished by canrenone, an inhibitor of ouabain, and (vii) ammonia-induced cell swelling depends on signaling via the Na,K-ATPase/ouabain/Src/EGF receptor/PI3K-AKT/ERK1/2, but in response to 3mM ammonia it does not appear until after 12h. Based on literature data it is suggested that the delayed appearance of the ammonia-induced swelling at this concentration reflects required ouabain-induced oxidative damage of the ion and water cotransporter NKCC1. This information may provide new therapeutic targets for treatment of hyperammonic brain disorders.

The aims of the current study were to investigate the influence of insufficient radiofrequency ablation (RFA) on the cell proliferation of the human hepatocellular carcinoma (HCC) cells, SMMC7721, and to elucidate the underlying mechanism. SMMC7721 cells were subjected to a 47°C treatment regimen to simulate insufficient RFA, in the presence or absence of KN93 [a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII)], PD98059 [a specific inhibitor of extracellular signal-regulated kinase (ERK)], or axitinib (a specific inhibitor of vascular endothelial growth factor (VEGF) receptor]. Cell proliferation was determined using a thiazolyl terazolium assay (MTT). The levels of CaMKII, phospho-CaMKII, ERK, phospho-ERK and VEGF were observed by western blot analysis. The results demonstrated that the 47°C treatment regimen: i) Triggered upregulation of VEGF expression in the SMMC7721 cells, which was reduced by CaMKII or ERK inhibition; ii) induced ERK activation was prevented by KN93; and iii) promoted SMMC7721 cell proliferation, which was greatly inhibited by axitinib, KN93 and PD98059. In conclusion, the results indicated that insufficient RFA promotes SMMC7721 cell proliferation by activating CaMKII/ERK-dependent VEGF overexpression.

In this work, a surface-flow constructed wetland (SFCW) dominated by Cladophora was used to remove and reclaim nutrients in diffuse domestic effluent (DDE) discharged from rural regions around Taihu Lake, a eutrophic shallow lake in China. Growth rate of Cladophora was investigated and linked to ambient factors and nutrient consuming rates. The growth performances of Cladophora and animal-feed microbes were studied during the commissioning of SFCW. Results show that the growth rate of Cladophora was closely correlated with field temperature and surface irradiance, while surface coverage was suitable for the manipulation of SFCW. Harvest of Cladophora along with animal-feed microbes and removal of nutrients in DDE could be achieved by manipulating surface coverage to drag growth rate back at the end of linear zone and to quickly restore Cladophora biomass in the mid zone of surface growth rate. Among four stages of the commissioning, concentrating stage experienced the majority species of animal-feed microbes and maximal nutrient removal; during decomposing stage, however, the reproduction of animal-feed microbes and nutrient removal were lower, whereas the density of pathogens was higher.

Evidence concerning the effects of different chemical components of particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) on asthma is limited, and the methodology to compare the relative importance of different PM2.5 components is lacking.

Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed. NDV entry into cells triggers Rac1-Pak1 signaling and elicits actin rearrangement and plasma membrane ruffling. Moreover, NDV internalization within macropinosomes and trafficking involve Rab5a-positive vesicles. This is the first report demonstrating that NDV utilizes clathrin-mediated endocytosis and macropinocytosis as alternative endocytic pathways to enter cells. These findings shed new light on the molecular mechanisms underlying NDV entry into cells, and provide potential targets for NDV-mediated therapy in cancer.

Most plant bacterial pathogens rely on type III effectors to cause diseases. Although it is well known that the plant hormone salicylic acid (SA) plays an essential role in defense, whether the master regulator of SA signaling, NPR1, is targeted by any plant pathogen effectors is unknown. SA facilitates the reduction of cytosolic NPR1 oligomers into monomers, which enter the nucleus and function as transcriptional coactivators of plant defense genes. We show that SA promotes the interaction between the Pseudomonas syringae type III effector AvrPtoB and NPR1. In the presence of SA, AvrPtoB mediates the degradation of NPR1 via the host 26S proteasome in a manner dependent on AvrPtoB's E3 ligase activity. Intriguingly, we found that NPR1 plays an important role in MAMP-triggered immunity (MTI), inducing the expression of MTI marker genes. Thus, this work uncovers a strategy in which AvrPtoB targets NPR1 and represses NPR1-dependent SA signaling, thereby subverting plant innate immunity.

Direct cultivation of the first filial generation of gametophyte clones from different Laminaria species is a highly effective way of utilizing kelp heterozygous vigor (heterosis). A male gametophyte clone of L. longissima Miyabe and a female one of L. japonica Areschoug were hybridized, generating Dongfang No. 2 hybrid kelp. This hybrid kelp was used directly in trial cultivation, and its agronomical traits were evaluated. L. longissima and L. japonica are obviously different and complement each other in their morphological characteristics and ecological performances. The hybrid of their gametophyte clones, Dongfang No. 2, showed 56.8% heterozygous vigor in yield. It also showed increased yields of 41.0 and 76.4% compared to the widely used commercial kelps Variety 1 and Variety 2, respectively. In large-scale cultivation trials at different locations and in different years, Dongfang No. 2 attained significantly higher yields than Varieties 1 and 2, increasing yield by 26.4% on average over Variety 1 and by 65.0% over the other. Dongfang No. 2 has a robust holdfast and a wide, long and deep-brown uniform blade, which shows a distinct middle groove. In addition to yield, Dongfang No. 2 also demonstrates obvious heterozygous vigor in other agronomic traits. It is resistant to strong irradiance, as the two commercial varieties are, has an appropriate vegetative maturation time, and adapts well to a range of different culture conditions. The parentage analysis using AFLP of total DNA and SNP of the ITS region of ribosomal RNA transcription unit showed that Dongfang No. 2 is the real hybrid of L. japonica and L. longissima.

Air quality models provide spatial fields of wet deposition (WD) and dry deposition that explicitly account for the transport and transformation of emissions from thousands of sources. However, many sources of uncertainty in the air quality model including errors in emissions and meteorological inputs (particularly precipitation) and incomplete descriptions of the chemical and physical processes governing deposition can lead to bias and error in the simulation of WD. We present an approach to bias correct Community Multiscale Air Quality model output over the contiguous United States using observation-based gridded precipitation data generated by the Parameter-elevation Regressions on Independent Slopes Model and WD observations at the National Atmospheric Deposition Program National Trends Network sites. A cross-validation analysis shows that the adjusted annual accumulated WD for NO3 -, NH4 +, and SO4 2- from 2002 to 2012 has less bias and higher correlation with observed values than the base model output without adjustment. Temporal trends in observed WD are captured well by the adjusted model simulations across the entire contiguous United States. Consistent with previous trend analyses, WD NO3 - and SO4 2- are shown to decrease during this period in the eastern half of the United States, particularly in the Northeast, while remaining nearly constant in the West. Trends in WD of NH4 + are more spatially and temporally heterogeneous, with some positive trends in the Great Plains and Central Valley of CA and slightly negative trends in the south.

Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity.

Aspirin has been reported for its anti-tumor activity, however, there are few studies on its effects in lung cancer. The present study found that aspirin had a dual role in the proliferation of human lung cancer PC-9 (formerly known as PC-14) and A549 cells, and in human colon cancer HCT116 cells. The cells were treated with 0, 1, 2, 4, 8 and 16 mM aspirin for 24-72 h or 7-12 days and cell proliferation was examined by MTT and colony formation assay. In order to explore the relationship between the proliferation-enhancing effect of low-dose aspirin and mitogen-activated protein kinase (MAPK) signaling activation, PC-9 cells were pretreated with 10 µM PD98059 (a specific inhibitor of ERK), SB203580 (a specific inhibitor of p38) and SP600125 (a specific inhibitor of JNK) for 30 min respectively. Western blot assay was performed to detect the activation of MAPK members in PC-9 cells. Cellular apoptosis was detected using flow cytometer-based Annexin V/propidium iodide dual staining. An assessment of MAPK inhibitors was performed to further validate the role of JNK, p38 and ERK in aspirin-promoted PC-9 cell growth. It was demonstrated that aspirin could promote the growth of human PC-9 lung cancer cells and induced MAPK activation at low concentrations. All the MAPK inhibitors tested (PD98059, SB203580 and SP600125) were able to inhibit the aspirin-induced proliferation of PC-9 cells.

Gliomas are the most common type of primary tumors in the central nervous system. This study aimed to investigate the biological role of miR-410-3p in glioma and elucidate the potential molecular mechanisms involved.

To explore the relationship between ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in ovarian cancer by the method of meta-analysis.

To evaluate the influence of screw-tightening methods on the immediate and long-term stability of dental implant screw joints. Methodology. A total of 150 implants of three different implant systems with different diameters were used in this study. Each group was divided into three subgroups (n = 5), according to the tightening methods (A-tightening with recommended torque and retorque after 10 min; B-tightening with recommended torque, then loosening and immediate retorque; C-tightening with recommended torque only once). The operating time of tightening the assemblies was recorded. Ten minutes later, the immediate removal torque (IRT) (Ncm) was measured. After retightening the assemblies, a dynamic load between 20 and 200 N was applied for 105 cycles, and the postloading removal torque (PRT) (Ncm) was measured. Scanning electron microscopy (SEM) was used to observe the surface topography of the screws.

Glioma is among the ten most common causes of cancer-related death and has no effective treatment for it, so we are trying to find a new target for anticancer treatment. This study investigates the different expression of SRPK1 as a novel protein in glioma, which can influence tumor cells biological characteristics in normoxic and hypoxic environment. The expression levels of SRPK1 protein in glioma cell lines transfected with siSRPK1 or not were examined using immunofluorescence, RT-PCR and Western blot analysis, respectively. The impact of SRPK1 on the biological characteristics of U251 cells was further studied using methylthiazol tetrazolium assays, flow cytometry, and Transwell invasion chamber assays. The results showed that knockdown of SRPK1 inhibited tumor cells growth, invasion and migration in normoxic condition, but portion of the effect could be reversed in hypoxia. SRPK1 expression was induced in glioma cells by DDP treated, but not TMZ, in both normoxia and hypoxia conditions. We propose SRPK1 as a new molecular player contributing to the early treatment of glioma.

Spinal cord injury is a severe clinical problem, and research searching activity molecular that can promote spinal cord injury repairing is very prevalent. Mst3b can promote repair of damaged peripheral nerves and the optic nerve, but has been rarely reported in spinal cord injury research. Through detecting its expression in different periods of injured spinal cord, we found that the expression of Mst3b was significantly upregulated in injured spinal cord neurons. Increasing Mst3b expression using adenovirus in vivo and in vitro promoted axonal regeneration of spinal cord neurons, which led to behavioral and electrophysiological improvement. Downregulation of Mst3b level had the adverse effects. Increasing Mst3b expression in PC12 cells resulted in an elevation of P42/44(MAPK) and LIMK/Cofilin activation. These results identified Mst3b as a powerful regulator for promoting spinal cord injury recovery through the P42/44(MAPK) and LIMK/Cofilin signaling pathways.