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N1 -methyladenosine (m1 A) is a prevalent and reversible RNA modification, which plays a crucial role in the regulation of RNA fate and gene expression. However, the lack of tools to precisely manipulate m1 A sites in specific transcripts has hindered efforts to clarify the association between a specific m1 A-modified transcript and its phenotypic outcomes. Here we develop a CRISPR-Cas13d-based tool called reengineered m1 A modification valid eraser (termed "REMOVER") for targeted m1 A demethylation of a specific transcript. The catalytically inactive RfxCas13d (dCasRx) is fused to the m1 A demethylase ALKBH3, and the dCasRx-ALKBH3 fusion protein can mediate potent demethylation of m1 A-modified RNAs. We further find that REMOVER can specifically demethylate m1 A of MALAT1 and PRUNE1 RNAs, thereby significantly increasing their stability. Our study establishes REMOVER as a tool for targeted RNA demethylation of specific m1 A-modified transcripts, which enables further elucidation of the relationship between m1 A modification of specific transcripts and their phenotypic outcomes.

Bisphenol A (BPA), a ubiquitous endocrine‐disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone‐dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAF V600E mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAF V600E mutation on epithelial‐mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAFV600E mutation and the level of EMT‐related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT‐related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAF V600E mutation. Moreover, ERK‐Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10‐7 M) synergized with the BRAF V600E mutation promoted EMT via the activation of ERK‐Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAF V600E mutation.

Planktonic microorganisms play a key role in the biogeochemical processes of the aquatic system, and they may be affected by many factors. High-throughput sequencing technology was used in this study to investigate and study the bacterioplankton community of water bodies in the upper reaches of the Heihe River Basin in Qinghai Plateau. Results showed that Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria are the predominant phyla in this river section, while the main genera are Thiomonas, Acidibacillus, Acidocella, Rhodanobacter, Acidithiobacter and Gallionella, which are autochthonous in the acid-mine drainage. Additionally, total nitrogen, total phosphorus, permanganate index and pH are significantly correlated with the bacterioplankton abundance and are the main limiting factors for the spatial distribution of the bacterioplankton. PICRUSt inferred that the mainstream microbial assemblages had a higher abundance of KOs belong to metabolism of terpenoids and polyketides, while the tributary had higher abundance of KOs belong to the immune system. The relationship between bacterioplankton community composition and environmental factors in the Heihe River basin was discussed for the first time in this study, which provides a theoretical basis for the healthy, orderly development of the water environment in the Heihe River Basin.

Stretchable electronics‐based surface electromyography (sEMG) evaluation devices are expected to play a big role in clinical diagnosis. However, the stability and quality of the signals collected by existing stretchable electronics are too poor, especially when muscle movement is involved, making them inappropriate for high standard clinical diagnosis. Here, a physiology‐based design method for stretchable electronics and a novel airbag‐type stretchable electrode array (ASEA) device for assessment of the complex female pelvic floor muscle (PFM) is proposed. Clinical trials show that the ASEA device is able to provide stable contact interface and multi‐channel accurate data acquisition. The stability and quality of the sEMG signal are much better than those obtained by the existing stretchable electronics‐based PFM electrode devices. Furthermore, a muscle‐unit evaluation method (MUEM) to assess the PFM complex state is proposed, especially its cross‐interaction between muscles. Clinical trials show that MUEM can accurately and comprehensively assess PFM state and the correlations between main muscles, which unveils the mechanisms of some special muscle states that are not possible using traditional methods. This proof of concept research holds the promise for the development of new diagnostic strategies for muscle pathological research, and has the potential for clinical application and general implication.

Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti-inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Our results showed that ISL exhibited cytotoxic effects on two human liver cancer cells in a dose-dependent manner. ISL significantly induced mitochondrial-related apoptosis and cell cycle arrest at the G2/M phase, which was accompanied by ROS accumulation in HepG2 cells. However, pretreatment with an ROS scavenger, N-acetyl-l-cysteine (NAC), inhibited ISL-induced apoptosis. In addition, ISL increased the phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 kinase and inhibitor of NF-κB (IκB), and decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB), these effects were blocked by NAC and mitogen-activated protein kinase (MAPK) inhibitors. Taken together, the findings of this study indicate that ISL induced HepG2 cell apoptosis via ROS-mediated MAPK, STAT3, and NF-κB signaling pathways. Therefore, ISL may be a potential treatment for human HCC, as well as other cancer types.

Hit, Lead & Candidate Discovery It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types.

A bidirectional punch-through transient voltage suppressor based on a five-layer N++P+PP+N++ structure is developed. By realizing the device using a 12-finger layout, transmission line pulse measurements indicate that the device has met the IEC61000-4-2 standard with electrostatic discharge robustness of ±8 kV and has an ultralow capacitance value of less than 0.17 pF. Under 3.3 V forward or reverse bias, the device exhibits a leakage current of less than 2 nA. These excellent figures suggest that the developed structure is well suited for actual system-level protection applications. © 2016 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

Lightweight, flexible and anisotropic porous multiwalled carbon nanotube (MWCNT)/water-borne polyurethane (WPU) composites are assembled by a facile freeze-drying method. The composites contain extremely wide range of MWCNT mass ratios and show giant electromagnetic interference (EMI) shielding effectiveness (SE) which exceeds 50 or 20 dB in the X-band while the density is merely 126 or 20 mg cm−3, respectively. The relevant specific SE is up to 1148 dB cm3 g−1, greater than those of other shielding materials ever reported. The ultrahigh EMI shielding performance is attributed to the conductivity of the cell walls caused by MWCNT content, the anisotropic porous structures, and the polarization between MWCNT and WPU matrix. In addition to the enhanced electrical properties, the composites also indicate enhanced mechanical properties compared with porous WPU and CNT architectures.

Short-term electricity load and price forecasting is an important issue in competitive electricity markets. In this paper, we propose a new direct time series forecasting method based on clustering and next symbol prediction. First, the cluster label sequence is obtained from time series clustering. Then a lossless compression algorithm of prediction by partial match version C coder (PPMC) is applied on this obtained discrete cluster label sequence to predict the next cluster label. Finally, the whole time series values of one-step-ahead can be directly forecast from the predicted cluster label. The proposed method is evaluated on electricity time series datasets, and the numerical experiments show that the proposed method can achieve promising results in day-ahead electricity load and price forecasting. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.