Upregulation of SMAD4 inhibits thyroid cancer cell growth via MAPK/JNK pathway repression

Purpose: To investigate whether the effect of mothers against decapentaplegic homolog 4 (SMAD4) on thyroid cancer cell survival was via the MAPK/JNK pathway. Methods: Papillary thyroid cancer (TPC)-1 cells were cultured and transfected with SMAD4 overexpression plasmid or siRNA to achieve SMAD4 overexpression or knockdown, respectively. In TPC-1 cells, the mRNA and protein expression levels of SMAD4, mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) were quantified using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Cell viability and apoptosis were measured using MTT assay and flow cytometry, respectively. MAPK and JNK inhibitors (U0126 and SP600125) were used for rescue experiments. The sensitivity of TPC-1 cells to chemotherapeutic drugs, cisplatin and doxorubicin, was also assessed. Results: A reduction in viability and an enhancement in apoptosis (p < 0.01) were found when SMAD4 was overexpressed in TPC-1 cells. Knockdown of SMAD4 elicited opposite results (p < 0.01). Overexpression of SMAD4 caused a decrease in the activation of MAPK and JNK, as evidenced by lower levels of phosphorylated MAPK and phosphorylated JNK (p < 0.05). Results from rescue experiments indicate that the increase in cell viability after SMAD4 knockdown was reversed by MAPK/JNK inhibitors (p < 0.05 and p < 0.01). Finally, overexpression of SMAD4 increased cytotoxic susceptibility of thyroid cancer cells to cisplatin/doxorubicin. Conclusion: These results indicate that SMAD4 inhibits thyroid cancer cell growth via inactivation of MAPK/JNK pathway. Overexpression of SMAD4 also increased thyroid cancer cell sensitivity to cisplatin/doxorubicin

Numerical Simulation on the Gas Explosion Propagation Related to Roadway

AbstractBased on the combustion, explosions and air dynamics and related theory etc, this paper describes the mathematical model of gas explosion in detail, combined with the gas explosion transmission mechanism, make a research on two wave-three area structure of gas explosion and the energy change rule of the array face of precursor wave and the array face of flame wave, with the fluid dynamics analysis Fluent software, this paper makes a numerical simulation and analysis on the overpressure transmission rule when gas explosion takes place in different types roadways. The results of the study show that: Fluent software can be used to accurately simulate gas explosion condition, when explosion wave spreads in the roadway turns, the bigger of the overpressure value in corner, the stronger of the destructive power; when tunnel has bifurcation, the overpressure will release in bifurcation, but explosions wave with flame wave will produce more powerful destruction effect. The research results can be used as a certain reference for how to prevent and control the gas explosion, and how to reduce the power of the gas explosion etc

Corticosteroids showed more efficacy in treating hospitalized patients with COVID-19 than standard care but the effect is minimal: A systematic review and meta-analysis

BackgroundDuring the ongoing coronavirus disease 2019 (COVID-19) pandemic, the use of corticosteroids for COVID-19 has ignited worldwide debate. Previous systematic reviews, including randomized controlled trials (RCTs) and retrospective observational studies, found that corticosteroids have beneficial effects in treating COVID-19.AimThis systematic review and meta-analysis only included RCTs to assess the effectiveness and safety of corticosteroids in hospitalized patients with COVID-19.MethodsComprehensive research strategies (PubMed, Embase, MEDLINE, and Coherence Library) were used to search for RCTs from December 2019 to January 2021.ResultsFive RCTs were included with 7,235 patients, of which 2,508 patients were receiving corticosteroid treatments (dexamethasone or methylprednisolone), and 4,727 received standard care. The primary outcome was mortality within 28 days. The use of corticosteroids decreased the 28-day mortality of patients with COVID-19, but the findings were not statistically significant (RR, 0.91; 95% CI, 0.78–1.06, p = 0.24). The secondary outcome was the duration of hospitalization; no differences were found between the corticosteroid and standard care groups. However, corticosteroids were associated with a higher hospital discharge rate than standard treatment, but the result was not statistically significant (RR, 1.36; 95% CI, 0.95–1.96, p = 0.09).ConclusionsThe results suggest that corticosteroids are comparable to standard care in terms of safety in treating COVID-19. Corticosteroids showed greater efficacy than standard care; however, the effect was minimal

Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells

The authors thank Sue Moreau from the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for English language editing of the manuscript. Author contributions: Study concept and design: M.I.A., P.A.Z, G.A.C. Acquisition of data: M.I.A., L.Z., X.Z. Drafting of the manuscript: M.I.A., M.N., R.S., M.F., R.M.R., P.A.Z, G.A.C. Analysis and interpretation of data: M.I.A., M.N., R.S., R.M., P.A.Z, G.A.C. Critical revision of the manuscript for important intellectual content: M.I.A., M.N., R.S., M.F., R.M.R., P.A.Z, G.A.C. Statistical analysis: M.I.A., C.I., L.X. Obtained funding: G.A.C. Administrative, technical, or material support: R.G., I.V., F.F., M.F., G.L. Study supervision: G.A.C. Drs Nicoloso and Spizzo are currently at the Division of Experimental Oncology, CRO, National Cancer Institute, Aviano, ItalyBackground & Aims MicroRNAs (miRNAs) can promote or inhibit tumor growth and are therefore being developed as targets for cancer therapies. They are diverse not only in the messenger RNAs (mRNA) they target, but in their production; the same hairpin RNA structure can generate mature products from each strand, termed 5p and 3p, that can bind different mRNAs. We analyzed the expression, functions, and mechanisms of miR-28-5p and miR-28-3p in colorectal cancer (CRC) cells. Methods We measured levels of miR-28-5p and miR-28-3p expression in 108 CRC and 49 normal colorectal samples (47 paired) by reverse transcription, quantitative real-time polymerase chain reaction. The roles of miR-28 in CRC development were studied using cultured HCT116, RKO, and SW480 cells and tumor xenograft analyses in immunodeficient mice; their mRNA targets were also investigated. Results miR-28-5p and miR-28-3p were down-regulated in CRC samples compared with normal colon samples. Overexpression of miRNAs in CRC cells had different effects and the miRNAs interacted with different mRNAs: miR-28-5p altered expression of CCND1 and HOXB3, whereas miR-28-3p bound NM23-H1. Overexpression of miR-28-5p reduced CRC cell proliferation, migration, and invasion in vitro, whereas miR-28-3p increased CRC cell migration and invasion in vitro. CRC cells overexpressing miR-28 developed tumors more slowly in mice compared with control cells, but miR-28 promoted tumor metastasis in mice. Conclusion miR-28-5p and miR-28-3p are transcribed from the same RNA hairpin and are down-regulated in CRC cells. Overexpression of each has different effects on CRC cell proliferation and migration. Such information has a direct application for the design of miRNA gene therapy trials.M.I.A. is supported by a PhD fellowship (SFRH/BD/47031/2008) from Fundação para a Ciência e Tecnologia, Portugal. G.A.C. is supported as a fellow by The University of Texas MD Anderson Cancer Center Research Trust, The University of Texas System Regents Research Scholar, and the Chronic Lymphocytic Leukemia Global Research Foundation. Work in Dr Calin’s laboratory is supported in part by grants from the National Institutes of Health (CA135444), the US Department of Defense, the Pancreatic Cancer Action Network (2009 Seena Magowitz AACR Pilot Grant), and the US-European Alliance for the Therapy of Chronic Lymphoid Leukemia. STR DNA fingerprinting was done by the Cancer Center Support grant funded Characterized Cell Line core, NCI # CA16672

Genome Sequence and Transcriptome Analysis of the Radioresistant Bacterium Deinococcus gobiensis: Insights into the Extreme Environmental Adaptations

The desert is an excellent model for studying evolution under extreme environments. We present here the complete genome and ultraviolet (UV) radiation-induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the cold Gobi desert and shows higher tolerance to gamma radiation and UV light than all other known microorganisms. Nearly half of the genes in the genome encode proteins of unknown function, suggesting that the extreme resistance phenotype may be attributed to unknown genes and pathways. D. gobiensis also contains a surprisingly large number of horizontally acquired genes and predicted mobile elements of different classes, which is indicative of adaptation to extreme environments through genomic plasticity. High-resolution RNA-Seq transcriptome analyses indicated that 30 regulatory proteins, including several well-known regulators and uncharacterized protein kinases, and 13 noncoding RNAs were induced immediately after UV irradiation. Particularly interesting is the UV irradiation induction of the phrB and recB genes involved in photoreactivation and recombinational repair, respectively. These proteins likely include key players in the immediate global transcriptional response to UV irradiation. Our results help to explain the exceptional ability of D. gobiensis to withstand environmental extremes of the Gobi desert, and highlight the metabolic features of this organism that have biotechnological potential

Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A “Leaky” Vaccine with Debatable Efficacy and Safety

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the late 1980s. Attributed to the PRRSV extensive genetic and antigenic variation and rapid mutability and evolution, nearly worldwide epidemics have been sustained by a set of emerging and re-emerging virus strains. Since the first modified live virus (MLV) vaccine was commercially available, it has been widely used for more than 20 years, for preventing and controlling PRRS. On the one hand, MLV can induce a protective immune response against homologous viruses by lightening the clinical signs of pigs and reducing the virus transmission in the affected herd, as well as helping to cost-effectively increase the production performance on pig farms affected by heterologous viruses. On the other hand, MLV can still replicate in the host, inducing viremia and virus shedding, and it fails to confer sterilizing immunity against PRRSV infection, that may accelerate viral mutation or recombination to adapt the host and to escape from the immune response, raising the risk of reversion to virulence. The unsatisfied heterologous cross-protection and safety issue of MLV are two debatable characterizations, which raise the concerns that whether it is necessary or valuable to use this leaky vaccine to protect the field viruses with a high probability of being heterologous. To provide better insights into the immune protection and safety related to MLV, recent advances and opinions on PRRSV attenuation, protection efficacy, immunosuppression, recombination, and reversion to virulence are reviewed here, hoping to give a more comprehensive recognition on MLV and to motivate scientific inspiration on novel strategies and approaches of developing the next generation of PRRS vaccine

Lightweight Small Target Detection Algorithm with Multi-Feature Fusion

Unmanned aerial vehicles (UAVs) are a highly sought-after technology with numerous applications in both military and non-military uses. The identification of targets is a crucial aspect of UAV applications, but there are challenges associated with complex detection models and difficulty in detecting small targets. To address these issues, this study proposes the lightweight L-YOLO algorithm for target detection tasks from a UAV perspective. The L-YOLO algorithm improves on YOLOv5 by improving the model’s detection performance for small targets while reducing the number of parameters and computational effort. The GhostNet module replaces the relevant convolution in the YOLOv5 model to create a lightweight model. The EIoU loss is used as the loss function of the algorithm to accelerate convergence and improve regression accuracy. Furthermore, feature-level extensions based on YOLOv5 are implemented, and a new detection head is proposed to improve the model’s detection accuracy for small targets. The size of the anchor boxes is redesigned to suit the small targets using the K-means++ clustering algorithm. The experiments were conducted on the VisDrone-2022 dataset, and the L-YOLO algorithm demonstrated a reduction in computational effort by 42.42% and number of parameters by 48.6% compared to the original algorithm. Furthermore, recall and [email protected] improved by 2.1% and 1.4%, respectively. These results demonstrate that the L-YOLO algorithm not only has better detection performance for small targets but is also a lighter model, indicating promising prospects for target detection from a UAV perspective

Data collection in sensornets with heterogeneous duty cycles: pursuit of efficient opportunity

Abstract For sensornets with heterogeneous duty cycles, sensor nodes wake up with different sleeping periods, which combined with unreliable links, making it very challenging to enhance the network performance. This paper presents a new opportunistic routing protocol, called EOF (Efficient Opportunistic Forwarding), which mainly involves a forwarding metric that can efficiently exploit the single-hop forwarding opportunity and a delay-aware forwarder selection scheme. Different from previous opportunistic routings for sensornets, EOF comprehensively considers the effect of heterogeneous duty cycles and link unreliability on the overall network performance. The experimental results show that compared to the state-of-the-art protocol, EOF can achieve better overall network performance with almost identical energy cost, especially when it is applied to the sensornet with significant heterogeneity of duty cycle