Osteosarcoma(OS) is the most common and aggressive malignant bone sarcoma,which occurs in rapidly growing bones in children and adolescents. However, the underlying molecular mechanisms of OS ...development have not been fully illustrated. N6-Methyladenosine (m6A) is the most prevalent internal chemical modification of mRNAs, which is involved in many pathological processes in cancer development. However, its role and regulatory mechanism in OS remain unknown. In this study, we aimed to investigate the roles of m6A and its methyltransferase METTL3 in OS development. The results showed that m6A level for RNA methylation and the expression level of METTL3 were up-regulated in human OS tissues and OS cell lines. Functionally, lentivirus-mediated METTL3 silence in HOS and SAOS-2 cells inhibited the cell proliferation, migration and invasion ability. Further mechanism analysis suggested that METTL3 silence decreased the m6A methylation and total mRNA level of lymphoid enhancer-binding factor 1 (LEF1), followed by inhibited the activity of Wnt/β-catenin signaling pathway. Moreover, LEF1 over-expression abrogates the repressive effects of METTL3 silence on the proliferation, migration and invasion abilities of OS cells. Together, these results revealed that the m6A methyltransferase METTL3 promotes osteosarcoma cell progression by regulating the m6A level of LEF1 and activating Wnt/β-catenin signaling pathway.
•The m6A methylated RNA level and the expression level of METTL3 were elevated in human OS tissues and cell lines.•METTL3 silence inhibits the cell proliferation, migration and invasion ability of OS cells in vitro and in vivo.•METTL3 silence decreases the m6A methylation and total mRNA level of LEF1, subsequently inhibited the activity of Wnt/β-catenin signaling pathway.
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•Cr(VI) was efficiently reduced to Cr(III) at alkaline pHs by UV/sulfite process.•Common ions and organic matters interfered with Cr(VI) reduction slightly.•Spontaneous precipitation ...of Cr(III) occurred in the presence of Ca2+ (>2ppm).•eaq− was identified as the dominant reactive species in UV/sulfite process.
Chemical reduction of Cr(VI) to Cr(III) followed by Cr(III) precipitation is a widely employed strategy to mitigate Cr(VI) pollution from industrial effluents. Nevertheless, most of the available reduction processes are feasible at acidic pHs only, and very few technologies are capable of reducing Cr(VI) at alkaline pHs. Herein, we demonstrated that the UV/sulfite process is very promising for alkaline Cr(VI) remediation, including the Cr(VI) reduction to Cr(III) and simultaneous Cr(III) precipitation. In this process Cr(VI) reduction followed near zero-order kinetics, declining with an increase of pH (5–10) but boosting with increasing sulfite concentration. The co-existing Cl− and SO42− in water exerted negligible effect on Cr(VI) reduction, whereas the reduction kinetics was improved in the presence of citrate, EDTA or humic acid possibly due to their complexation with Cr(III). Similarly, the presence of borate buffer would significantly inhibit Cr(VI) reduction to Cr(III) as well as the final Cr(III) removal during precipitation. Fortunately, the presence of calcium ions even at trace level would favor Cr(III) precipitation and result in one-step removal of the total Cr at alkaline pH. The mechanism of Cr(VI) reduction was probed through irradiation manipulation and N2O addition, and the results suggested that excitation of sulfite is essential for alkaline Cr(VI) reduction, and eaq− is the dominant reactive species in the UV/sulfite process.
Achieving active and stable oxygen evolution reaction (OER) in acid media based on single-atom catalysts is highly promising for cost-effective and sustainable energy supply in proton electrolyte ...membrane electrolyzers. Here, we report an atomically dispersed Ru
-N
site anchored on nitrogen-carbon support (Ru-N-C) as an efficient and durable electrocatalyst for acidic OER. The single-atom Ru-N-C catalyst delivers an exceptionally intrinsic activity, reaching a mass activity as high as 3571 A g
and turnover frequency of 3348 O
h
with a low overpotential of 267 mV at a current density of 10 mA cm
. The catalyst shows no evident deactivation or decomposition after 30-hour operation in acidic environment. Operando synchrotron radiation X-ray absorption spectroscopy and infrared spectroscopy identify the dynamic adsorption of single oxygen atom on Ru site under working potentials, and theoretical calculations demonstrate that the O-Ru
-N
site is responsible for the high OER activity and stability.
Water deficit is an abiotic stress that retards plant growth and destabilizes crop production. Long non coding RNAs (lncRNAs) are a class of non-coding endogenous RNAs that participate in diverse ...cellular processes and stress responses in plants. lncRNAs could function as competing endogenous RNAs (ceRNA) and represent a novel layer of gene regulation. However, the regulatory mechanism of lncRNAs as ceRNA in drought stress response is yet unclear.
In this study, we performed transcriptome-wide identification of drought-responsive lncRNAs in rice. Thereafter, we constructed a lncRNA-mediated ceRNA network by analyzing competing relationships between mRNAs and lncRNAs based on ceRNA hypothesis. A drought responsive ceRNA network with 40 lncRNAs, 23 miRNAs and 103 mRNAs was obtained. Network analysis revealed TCONS_00021861/miR528-3p/YUCCA7 regulatory axis as a hub involved in drought response. The miRNA-target expression and interaction were validated by RT-qPCR and RLM-5'RACE. TCONS_00021861 showed significant positive correlation (r = 0.7102) with YUCCA7 and negative correlation with miR528-3p (r = -0.7483). Overexpression of TCONS_00021861 attenuated the repression of miR528-3p on YUCCA7, leading to increased IAA (Indole-3-acetic acid) content and auxin overproduction phenotypes.
TCONS_00021861 could regulate YUCCA7 by sponging miR528-3p, which in turn activates IAA biosynthetic pathway and confer resistance to drought stress. Our findings provide a new perspective of the regulatory roles of lncRNAs as ceRNAs in drought resistance of rice.
Quantum key distribution (QKD) provides information-theoretic security based on quantum mechanics. Integrating QKD with classical data traffic by using wavelength division multiplexing (WDM) ...techniques in a single fibre is a cost-efficient way to improve security in legacy infrastructure. In such a system, the main noise source to the quantum channel is spontaneous Raman scattering (SRS) caused by the classical channels. In this letter we introduce a channel allocation strategy for both quantum and classical signals to minimize the SRS noise. A use case that quantum and classical channels co-exist in a dense WDM system is investigated. The results show >26% increase of achievable transmission distance for the QKD system when implementing the introduced channel allocation strategy. Moreover, a network updating plan is proposed, which provides a guideline to light the new wavelengths for classical communications while minimizing the SRS noise to quantum channels.
Clear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies. MicroRNAs (miRNAs) are post-transcriptional gene regulators in tumor pathophysiology. As miRNAs exert ...cooperative repressive effects on target genes, studying the miRNA synergism is important to elucidate the regulation mechanism of miRNAs.
We first created a miRNA-mRNA association network based on sequence complementarity and co-expression patterns of miRNA-targets. The synergism between miRNAs was then defined based on their expressional coherence and the concordance between target genes. The miRNA and mRNA expression were detected in RCC cell lines (786-O) using quantitative RT-PCR. Potential miRNA-target interaction was identified by Dual-Luciferase Reporter assay. Cell proliferation and migration were assessed by CCK-8 and transwell assay.
A synergistic miRNA-miRNA interaction network of 28 miRNAs (52 miRNA pairs) with high coexpression level were constructed, among which miR-124 and miR-203 were identified as most tightly connected. ZEB2 expression is inversely correlated with miR-124 and miR-203 and verified as direct miRNA target. Cotransfection of miR-124 and miR-203 into 786-O cell lines effectively attenuated ZEB2 level and normalized renal cancer cell proliferation and migration. The inhibitory effects were abolished by ZEB2 knockdown. Furthermore, pathway analysis suggested that miR-124 and miR-203 participated in activation of epithelial-to-mesenchymal transition (EMT) pathway via regulation of ZEB2.
Our findings provided insights into the role of miRNA-miRNA collaboration as well as a novel therapeutic approach in ccRCC.
The BET family proteins, comprising BRD2, BRD3 and BRD4, represent epigenetic readers of acetylated histone marks that play pleiotropic roles in the tumorigenesis and growth of multiple human ...malignancies, including glioblastoma (GBM). A growing body of investigation has proven BET proteins as valuable therapeutic targets for cancer treatment. Recently, several BRD4 inhibitors and degraders have been reported to successfully suppress GBM in preclinical and clinical studies. However, the precise role and mechanism of BRD4 in the pathogenesis of GBM have not been fully elucidated or summarized. This review focuses on summarizing the roles and mechanisms of BRD4 in the context of the initiation and development of GBM. In addition, several BRD4 inhibitors have been evaluated for therapeutic purposes as monotherapy or in combination with chemotherapy, radiotherapy, and immune therapies. Here, we provide a critical appraisal of studies evaluating various BRD4 inhibitors and degraders as novel treatment strategies against GBM.
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Increasing evidence has shown a link between immune cells and Alzheimer's disease (AD). Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal ...association between 731 immune cell signatures and AD in this study.
We extracted genetic variants of 731 immune cell traits and AD from the publicly available GWAS dataset. The immune features included median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC) and morphological parameters (MP). The inverse variance weighted (IVW) method was the main MR analysis method, and sensitivity analyses were used to validate the robustness, heterogeneity and horizontal pleiotropy of the results.
After FDR adjustment, seven immune phenotypes were found to be associated significantly with AD risk: HLA DR on CD33−HLA DR+ (OR = 0.938, PFDR = 0.001), Secreting Treg %CD4 (OR = 0.972, PFDR = 0.021), HLA DR+T cell AC (OR = 0.928, PFDR = 0.041), Activated & resting Treg % CD4 Treg (OR = 1.031, PFDR = 0.002), CD33 on CD33dim HLA DR+CD11b+ (OR = 1.025, PFDR = 0.025), CD33 on CD14+monocyte (OR = 1.026, PFDR = 0.027) and CD33 on CD66b++myeloid cell (OR = 1.027, PFDR = 0.036).
These findings demonstrated seven immune phenotypes were significantly associated with AD risk. This may provide researchers with a new perspective in exploring the biological mechanisms of AD and may lead to the exploration of earlier treatment.
•Increasing evidence has shown a link between immune cells and Alzheimer’ s disease (AD). Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between 731 immune cell signatures and AD in this study.•Seven immune phenotypes were found to be associated significantly with AD risk: HLA DR on CD33-HLA DR+, Secreting Treg %CD4, HLA DR+T cell AC, Activated & resting Treg % CD4 Treg, CD33 on CD33dim HLA DR+CD11b+, CD33 on CD14+monocyte and CD33 on CD66b++myeloid cell.•This may provide researchers with a new perspective in exploring the biological mechanisms of AD and may lead to the exploration of earlier treatment.
Security issues and attack management in transparent wavelength division multiplexing (WDM) optical networks have become of prime importance to network operators due to the high data rates involved ...and the vulnerabilities associated with transparency. Deliberate physical-layer attacks, such as high-powered jamming, can seriously degrade network performance and must be dealt with efficiently. While most approaches are focused on the developing fast detection and reaction mechanisms triggered in case of an attack, we propose a novel approach to help deal with these issues in the network planning and provisioning process as a prevention mechanism. Namely, we propose to route lightpaths in such a way as to minimize the potential damage caused by various physical-layer attacks. We present a new objective criterion for the routing and wavelength assignment (RWA) problem, which we call the maximum Lightpath Attack Radius ( maxLAR), and formulate the routing subproblem as an integer linear program (ILP). We test it on small networks to get an insight into its complexity and compare it to a formulation that minimizes congestion. Results indicate that our formulation achieves significantly better results for the maxLAR while obtaining near-optimal or optimal congestion in all cases. For larger networks, we propose a tabu search algorithm for attack-aware lightpath routing, in combination with an existing graph-coloring algorithm for wavelength assignment. Testing and comparing with existing approaches from literature indicate its superiority with respect to the maxLAR and average lightpath load, albeit at the expense of somewhat higher congestion. However, this is justified with the obtained improvement in network security.
•Menstrual blood-derived MSC transplantation lower mortality of H7N9-induced ARDS.•Prospective and systematic study of H7N9-induced pneumonia to assess health status.•MSC transplantation has not ...harmful effect in human body with long-term follow-up.•MSC-based therapy is an alternative way to treat COVID-19 in severe ARDS patient.
H7N9 viruses quickly spread between mammalian hosts and carry the risk of human-to-human transmission, as shown by the 2013 outbreak. Acute respiratory distress syndrome (ARDS), lung failure, and acute pneumonia are major lung diseases in H7N9 patients. Transplantation of mesenchymal stem cells (MSCs) is a promising choice for treating virus-induced pneumonia, and was used to treat H7N9-induced ARDS in 2013. The transplant of MSCs into patients with H7N9-induced ARDS was conducted at a single center through an open-label clinical trial. Based on the principles of voluntariness and informed consent, 44 patients with H7N9-induced ARDS were included as a control group, while 17 patients with H7N9-induced ARDS acted as an experimental group with allogeneic menstrual-blood-derived MSCs. It was notable that MSC transplantation significantly lowered the mortality of the experimental group, compared with the control group (17.6% died in the experimental group while 54.5% died in the control group). Furthermore, MSC transplantation did not result in harmful effects in the bodies of four of the patients who were part of the five-year follow-up period. Collectively, these results suggest that MSCs significantly improve the survival rate of H7N9-induced ARDS and provide a theoretical basis for the treatment of H7N9-induced ARDS in both preclinical research and clinical studies. Because H7N9 and the coronavirus disease 2019 (COVID-19) share similar complications (e.g., ARDS and lung failure) and corresponding multi-organ dysfunction, MSC-based therapy could be a possible alternative for treating COVID-19.
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