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With the ubiquitous deployment and applications of internet of things (IoT), security issues pose a critical challenge to IoT devices. External attackers often utilize vulnerable IoT devices to invade the target’s internal network and then further cause a security threat to the whole network. To prevent such attacks, it is necessary to develop a security mechanism to control the access of suspicious IoT devices and manage the internal devices. In recent years, deep learning (DL) algorithm has been widely used in the field of edge device identification (EDI), and has made great achievements. However, these previous methods are essentially centralized learning-based EDI (CentEDI) that trains all data together, which can not guarantee data security and not conducive to deployment on edge devices. To address this problem, we introduce a federated learning-based EDI (FedeEDI) method via network traffic to automatically identify edge devices connected to the whole network. Experimental results show that the training efficiency of our proposed FedeEDI method is much higher than that of the CentEDI method, although its classification accuracy is slightly reduced. In contrast to the CentEDI method, the proposed FedeEDI method has two main advantages: faster training speed and safer training process.

Resistance to HER2-targeted therapy represents a significant challenge for the successful treatment of patients with breast cancer with HER2-positive tumors. Through a global mass spectrometry–based proteomics approach, we discovered that the expression of the N6-methyladenosine (m6A) demethylase ALKBH5 was significantly upregulated in HER2-targeted therapy-resistant breast cancer cells. Elevated expression of ALKBH5 was sufficient to confer resistance to HER2-targeted therapy, and specific knockdown of ALKBH5 rescued the efficacy of trastuzumab and lapatinib in resistant breast cancer cells. Mechanistically, ALKBH5 promoted m6A demethylation of GLUT4 mRNA and increased GLUT4 mRNA stability in a YTHDF2-dependent manner, resulting in enhanced glycolysis in resistant breast cancer cells. In breast cancer tissues obtained from patients with poor response to HER2-targeted therapy, increased expression of ALKBH5 or GLUT4 was observed and was significantly associated with poor prognosis in the patients. Moreover, suppression of GLUT4 via genetic knockdown or pharmacologic targeting with a specific inhibitor profoundly restored the response of resistant breast cancer cells to trastuzumab and lapatinib, both in vitro and in vivo. In conclusion, ALKBH5-mediated m6A demethylation of GLUT4 mRNA promotes resistance to HER2-targeted therapy, and targeting the ALKBH5/GLUT4 axis has therapeutic potential for treating patients with breast cancer refractory to HER2-targeted therapies. Significance: GLUT4 upregulation by ALKBH5-mediated m6A demethylation induces glycolysis and resistance to HER2-targeted therapy and represents a potential therapeutic target for treating HER2-positive breast cancer.

Green development is inseparable from financial support. The impact of digital inclusive finance (DIF), an emerging financial format, on the green development efficiency (GDE) needs to be studied. Using the panel data of the Provincial Digital Financial Inclusion Index from 2011 to 2019, this paper examines the impact of DIF and its coverage breadth (CB), usage depth (UD), and digitalization level (DL) on GDE, and analyzes the regional heterogeneity of the impact of DIF on GDE. The research also explores the mechanism by which DIF affects the efficiency of provincial green development, including the moderating role of environmental regulation (ER) and the mediating role of industrial structure upgrade (ISU). The results show that DIF, UD, and DL can significantly improve provincial GDE, and the effect of coverage breadth is not obvious. From a regional perspective, DIF can promote GDE in the eastern and central regions, whereas it has no obvious effect on the western region. Moreover, ER has played a moderation role in the process of DIF affecting GDE. ISU has played a partial mediation role in the process of DIF affecting GDE. The research conclusions can provide relevant suggestions for the green development of China's provinces.

Resistance to HER2-targeted therapy represents a significant challenge for the successful treatment of patients with breast cancer with HER2-positive tumors. Through a global mass spectrometry–based proteomics approach, we discovered that the expression of the N6-methyladenosine (m6A) demethylase ALKBH5 was significantly upregulated in HER2-targeted therapy-resistant breast cancer cells. Elevated expression of ALKBH5 was sufficient to confer resistance to HER2-targeted therapy, and specific knockdown of ALKBH5 rescued the efficacy of trastuzumab and lapatinib in resistant breast cancer cells. Mechanistically, ALKBH5 promoted m6A demethylation of GLUT4 mRNA and increased GLUT4 mRNA stability in a YTHDF2-dependent manner, resulting in enhanced glycolysis in resistant breast cancer cells. In breast cancer tissues obtained from patients with poor response to HER2-targeted therapy, increased expression of ALKBH5 or GLUT4 was observed and was significantly associated with poor prognosis in the patients. Moreover, suppression of GLUT4 via genetic knockdown or pharmacologic targeting with a specific inhibitor profoundly restored the response of resistant breast cancer cells to trastuzumab and lapatinib, both in vitro and in vivo. In conclusion, ALKBH5-mediated m6A demethylation of GLUT4 mRNA promotes resistance to HER2-targeted therapy, and targeting the ALKBH5/GLUT4 axis has therapeutic potential for treating patients with breast cancer refractory to HER2-targeted therapies.Significance:GLUT4 upregulation by ALKBH5-mediated m6A demethylation induces glycolysis and resistance to HER2-targeted therapy and represents a potential therapeutic target for treating HER2-positive breast cancer.

Methods and Materials

Table S2. Correlation of HSP27 level with clinicopathological parameters in cohort1; Table S3. Correlation of HSP27 level with clinicopathological parameters in cohort2.

Figure S1, related to Figure 1. THAP9-AS1 as a lncRNA is upregulated in PDAC.

Figure S3, related to Figure 3. THAP9-AS1 enables PDAC cells growth via enhancing YAP activation.

Figure S5, related to Figure 5. THAP9-AS1 interacts with YAP to block LATS1-mediated YAP phosphorylation.

Purpose: Squamous cell carcinoma of tongue (SCCT) is the most common type of oral cavity carcinoma. Chemoresistance in SCCT is common, and the underlying mechanism remains largely unknown. We aimed to identify key molecules and signaling pathways mediating chemoresistance in SCCT.Experimental Design: Using a proteomic approach, we found that the HSP27 was a potential mediator for chemoresistance in SCCT cells. To further validate this role of HSP27, we performed various mechanistic studies using in vitro and in vivo models as well as serum and tissue samples from SCCT patients.Results: The HSP27 protein level was significantly increased in the multidrug-resistant SCCT cells and cell culture medium. Both HSP27 knockdown and anti-HSP27 antibody treatment reversed chemoresistance. Inversely, both HSP27 overexpression and recombinant human HSP27 protein treatment enhanced chemoresistance. Moreover, chemotherapy significantly induced HSP27 protein expression in both SCCT cells and their culture medium, as well as in tumor tissues and serum of SCCT patients. HSP27 overexpression predicts a poor outcome for SCCT patients receiving chemotherapy. Mechanically, extracellular HSP27 binds to TLR5 and then activates NF-κB signaling to maintain SCCT cell survival. TLR5 knockdown or restored IκBα protein level disrupts extracellular HSP27-induced NF-κB transactivation and chemoresistance. Moreover, intracellular HSP27 binds to BAX and BIM to repress their translocation to mitochondrion and subsequent cytochrome C release upon chemotherapy, resulting in inhibition of the mitochondrial apoptotic pathway.Conclusions: HSP27 plays a pivotal role in chemoresistance of SCCT cells via a synergistic extracellular and intracellular signaling. HSP27 may represent a potential biomarker and therapeutic target for precision SCCT treatment. Clin Cancer Res; 24(5); 1163–75. ©2017 AACR.

Figure S2, related to Figure 2. THAP9-AS1 promotes PDAC growth.

Suppl. Data

Table S1. Identified differential protein spots between SCC-15 and SCC-15/PYM cell lines.

Supplementary Figures S1-7. Supplementary Figure S1. Analysis of TET1/2/3 expression and 5-hmC levels in GC specimens and cell lines; Supplementary Figure S2. Effect of TETs on GC cell cycle, apoptosis and invasion; Supplementary Figure S3. Diagram of different recombinant expression vectors containing the TET1/2 5''UTR, the TET1/2/3 CDS, the TET1/2/3 3''UTR and the TET1/2/3 3''UTR with mutation of miR-26 binding sites as well as the TET1/2/3 full-length cDNA; Supplementary Figure S4. The expression levels of TET1, TET2 and TET3 in MKN-28 cells transfected with TET1/2/3 5''UTR, CDS, 3''UTR and full-length cDNA plasmids or empty vector; Supplementary Figure S5. TETs are direct targets of miR-26 in GC cells; Supplementary Figure S6. The regulatory role of TETs in the expression of EZH2; Supplementary Figure S7. TETs co-localize with miR-26 and EZH2 in the cytoplasm of GC cells.

Description of additional experimental methods including vector construction, absolute quantification of mRNA and miRNA, RNA ï¬,uorescence in situ hybridization, and dot blotting.

Suppl. Figures 1-6

Supplementary Data from ALKBH5-Mediated m6A Demethylation of GLUT4 mRNA Promotes Glycolysis and Resistance to HER2-Targeted Therapy in Breast Cancer

DNA demethylases of the TET family function as tumor suppressors in various human cancers, but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here, we report that TET is transcriptionally upregulated in gastric cancer, where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a noncoding function of the 3′UTR, which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby led to EZH2 overexpression in gastric cancer. Our findings uncover a novel noncoding function for TET family proteins in facilitating gastric carcinogenesis. Cancer Res; 77(22); 6069–82. ©2017 AACR.

Supplementary Tables S1-3. Supplementary Table S1. Clinicopathological characteristics of GC patients; Supplementary Table S2. Primers used for qRT-PCR; Supplementary Table S3. Correlation between clinicopathological parameters and TET transcriptional levels in GC patients.

Figure S4, related to Figure 4. THAP9-AS1 increases YAP expression by sponging miR-484.

Guided tissue regeneration (GTR) membranes not only can hamper undesirable tissues down-growth into the defects but also can selectively promote the in-growth of regenerative bone tissue, playing a critical role in periodontal regeneration. Herein, a bi-layered electrospun membrane with different sized pores was designed and fabricated by adjusting electrospinning parameters combing with facile two-step electrospinning. The small-sized pore layer (SL) as occlusive layer consisted of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibers, while the macroporous osteoconductive layer (ML) was attained via introducing the nano-hydroxyapatite (nHA) particles into PLGA nanofibers during electrospinning. Morphological results such as surface topography, nanofiber size, and pore size distribution, showed that the SL exhibited a dense structure with pore size mainly from 4 to 7 μm. In contrast, the ML possessed a loosely packed structure with pore size mainly from 20 to 28 μm, which was beneficial to the infiltration of the cells. Fourier transform infrared spectroscopy (FTIR), Energy dispersive spectrometer (EDS), and X-ray diffractometry (XRD) results showed that nHA particles were evenly loaded in PLGA nanofibers. In vitro biodegradation tests suggested that the bi-layered membrane possessed a proper degradation timeframe, which must function for at least 4 to 6 weeks. The cell experiments indicated that the bi-layered electrospun membrane possessed good cytocompatibility and proved the effective barrier potency of the small-sized pore layer. Furthermore, as revealed by the alkaline phosphate activity test, the PLGA/nHA layer possessed an improved osteogenic capacity for Human osteosarcoma cells (MG63). These results indicate that the bi-layered electrospun membrane may have potential for periodontal tissue regeneration.

The surface-enhanced Raman scattering (SERS) technique has displayed a broad application prospect in disease diagnosis owing to its high sensitivity, fast responsiveness, and high specificity. In this study, we developed a SERS-based immunoassay for the detection of cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM), which is an important biomarker of cryptococcosis. The coupled localized surface plasmon resonance effect between magnetic SERS substrates and SERS tags gave rise to an enhanced Raman signal upon the formation of sandwich complexes, which contributes to the sensitive and specific detection of GXM. As a result, the developed method provided a lower limit of detection (1.25 ng/mL) than conventional methods, such as latex agglutination, lateral flow assay, and enzyme-linked immunosorbent assay. Additionally, a recovery experiment was performed to detect GXM in human serum, which also validated the potential advantages of a SERS-based immunoassay in the clinical diagnosis of cryptococcosis.

Fullerene (C70) molecules are assembled into microrods, and calcination breaks the carbon cages into defect-rich porous carbon microrods that show excellent ORR performance, comparable to commercial Pt/C.

We report a simple and green protocol to produce phenazine from lignin-derived catechol in a one-pot reaction. Phenazine was obtained in the form of high purity (>97%) crystals.

We report an easy protocol based on extraction and crystallization to isolate and purify 4-propylguaiacol and 4-propylsyringol from RCF-based products. GC purities reached 93.1% and 98.3%, respectively.

YAP (gene symbol

Nanocellulose has become a hotspot in the field of green and sustainable materials. The research status of nanocellulose in cleaner production and its environmental assessments were reviewed.

Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) is a multifunctional mediator of the conserved MAPK signaling pathway that plays essential roles in the regulation of immune responses in mammals. However, the function of teleost MAP3K4s in innate immunity, especially in the intestinal immune system, is still poorly understood. In the current study, we identified a fish MAP3K4 homolog (CiMAP3K4) in Ctenopharyngodon idella as well as its immune function in intestine following bacterial infection in vivo and in vitro. The open reading frame (ORF) of CiMAP3K4 encodes putative peptide of 1544 amino acids containing a predicted serine/threonine protein kinase (S_TKc) domain with high identity with other fish MAP3K4s. Phylogenetic analysis revealed the CiMAP3K4 belonged to the fish cluster and showed the closest relationship to Pimephales promelas. Quantitative real-time PCR (qRT-PCR) analysis revealed that CiMAP3K4 transcripts were widely distributed in all tested tissues, especially with high expression in the muscle and intestine of healthy grass carp. In vitro, CiMAP3K4 gene expression was upregulated by bacterial PAMPs (lipolysaccharide (LPS), peptidoglycan (PGN), L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP) and muramyl dipeptide (MDP)) and pathogens (Aeromonas hydrophila and Aeromonas veronii) in primary intestinal cells. In vivo, the mRNA expression levels of CiMAP3K4 in the intestine were significantly induced by bacterial MDP challenge in a time-dependent manner; however, this effect could be inhibited by the bioactive dipeptides β-alanyl- l -histidine (carnosine) and alanyl-glutamine (Ala-Gln). Moreover, CiMAP3K4 was located primarily in the cytoplasm, and its overexpression increased the transcriptional activity of AP-1 in HEK293T cells. Collectively, these results suggested that CiMAP3K4 might play an important role in the intestinal immune response to bacterial infections, which paves the way for a better understanding of the intestinal immune system of grass carp.

Background New-onset neurological symptoms such as numbness and pain in lower extremities might appear immediately after conventional lumbar interbody fusion (LIF) surgery performed in patients with lumbar spinal stenosis. Methods and Analysis: This is a multicenter, randomized, open-label, parallel-group, active-controlled trial investigating the clinical outcomes of modified LIF sequence versus conventional LIF sequence in treating patients with lumbar spinal stenosis. A total of 254 eligible patients will be enrolled and randomized in a 1:1 ratio to either modified LIF sequence or conventional LIF sequence group. The primary outcome measure is the perioperative incidence of new-onset lower extremity neurological symptoms, including new adverse events of pain, numbness, and foot drop of any severity. Important secondary endpoints include visual analogue scale (VAS) pain score and lumbar Japanese Orthopaedic Association (JOA) recovery rate. Other safety endpoints will also be evaluated. The safety set used for safety data analysis by the actual surgical treatment received and the full analysis set for baseline and efficacy data analyses according to the intent-to-treat principle will be established as the two analysis population in the study. Conclusion This study is designed to investigate the clinical outcomes of modified LIF sequence in patients with lumbar spinal stenosis. It aims to provide clinical evidence that the modified “fixation-fusion” sequence of LIF surgery is effective in treating lumbar spinal stenosis. (Words: 221) Trial registration: http://www.chictr.org.cn/index.aspx ID: ChiCTR2100048507