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Conductive hydrogels (CHs) are ideal electrolyte materials for the preparation of flexible supercapacitors (FSCs) due to their excellent electrochemical properties, mechanical properties, and deformation restorability. However, most of the reported CHs are prepared by the chemical crosslinking of synthetic polymers and thus usually display the disadvantages of poor self-healing abilities and nonadaptability at environmental temperatures, which greatly limits their application. To overcome these problems, in the present work, we constructed a sodium alginate-borax/gelatin double-network conductive hydrogel (CH) by a dynamic crosslinking between sodium alginate (SA) and borax via borate bonds and hydrogen bonding between amino acids in gelatin and SA chains. The CH displays an excellent elongation of 305.7% and fast self-healing behavior in 60 s. Furthermore, a phase-change material (PCM), Na

Background. Thyroid carcinoma (TC) is an increasingly common malignancy of endocrine organs, and its most frequently encountered histotype is papillary thyroid cancer (PTC). Identifying new potential gene alterations is important for completely elucidating the mechanism of PTC initiation and progression. Thus, we performed whole transcriptome sequence analysis (RNA-seq) on 79 PTC tissue samples and paired adjacent nontumor tissue samples to study the molecular mechanism of TC tumorigenesis and progression further. The results of RNA-seq analysis showed that spectrin beta, nonerythrocytic 2 (SPTBN2), was markedly overexpressed in PTC tissues relative to that in the paired nontumor tissues. Additionally, the analysis results for 502 PTC samples and 58 nontumor thyroid samples from The Cancer Genome Atlas dataset were consistent with our RNA-seq results. However, the molecular mechanisms and function of SPTBN2 in TC progression remain unknown. Methods. We examined SPTBN2 gene expression in 48 papillary thyroid tumor tissues and paired adjacent normal thyroid tissues by using qRT-PCR. SPTBN2 expression in the TC cell lines was silenced by small interfering RNA. Then, the transfected TC cells were used to investigate the in vitro function of SPTBN2. Result. The expression of SPTBN2 was significantly upregulated in our RNA-seq cohort, our local validated cohort, and TCGA RNA-seq cohort. The results of the in vitro experiment revealed that in TC cell lines, SPTBN2 downregulation considerably suppressed tumor cell proliferation, the cell cycle, migration, colony formation, and invasion and induced cell apoptosis. Furthermore, the protein levels of CCNE2, CDK2, CDK4, and Bcl-2 were downregulated, and those of P21, Bax, cleaved caspase-8, and cleaved caspase-3 had increased in transfected TC cells relative to in control TC cells. Conclusion. The downregulation of SPTBN2 caused apoptosis and retarded G1/S cell cycle transition in TC cells. Thus, SPTBN2 may be a good candidate gene for TC diagnosis and therapy.

Background: Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays. Methods: To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion apoptosis, and of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting. Results: Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown. Conclusion: In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.

Breast cancer (BC) threatened the life health of a tremendous amount of the population, and the estimated number of death is still rising nowadays. We found that stress-induced phosphoprotein 1 (STIP1) is overexpressed in BC tissues compared to non-tumorous breast tissues. Our study is to validate the prognostic value of STIP1 and investigate its biological role in BC. We verified the upregulation of STIP1 in multiple databases, proved that STIP1 is upregulated in BC tissues and cell lines using real-time quantitative PCR (qRT-PCR). We used small interfering RNA to examine the function of STIP1 in BC cell lines (BT-549, MDA-MB-231, Hs-578 T) and explored the mechanism of function of STIP1 in BC cells using Western blotting and qRT-PCR. Analyses of multiple databases indicated that high STIP1 expression is a marker that effectively distinguishes BC patients from healthy control and predicts worse clinical outcomes in BC. The loss-of-function experiments showed that STIP1 silencing results in inhibition of cell proliferation and migration, inducing cell apoptosis, and S-phase arrest in vitro. Our study also showed that STIP1 downregulation inhibited the JAK2/STAT3 pathway and epithelial-mesenchymal transition process. Rescue experiments demonstrated that the oncogenic effect of STIP1 is partially dependent on mediating JAK2 expression. This study verified that STIP1 is an oncogenic gene that promotes BC progression and serves as a valuable diagnostic and outcome-related marker of BC.

The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up‐regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf‐like PTC patients with higher IMUP expression had shorter disease‐free survival. The biological function of IMUP in PTC cell lines (KTC‐1 and TPC‐1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis‐related molecules were identified by real‐time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down‐regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.

Introduction Breast cancer (BC) is one of the most prevalent malignancies in women and its incidence has increased steadily over recent years (0.3% per year). However, the mechanism of BC tumorigenesis remains elaborate elucidation. With the aid of RNA sequencing technology, we discovered that immortalization-upregulated protein (IMUP) is overexpressed in BC tissues compared to normal breast tissues. Our study is to understand the role of IMUP in BC. Methods We validated the upregulation of IMUP from multiple public databases. By using quantitative real-time polymerase chain reaction (qRT-PCR), we proved that IMUP is overexpressed in BC tissues and cell lines. We performed proliferation, migration, invasion and apoptosis assays to explore the function of IMUP in BC cell lines (MCF-7 and MDA-MB-231). Besides, we investigated the effect of IMUP silencing on epithelial-mesenchymal transition using Western blotting and qRT-PCR. Results and discussion We validated that IMUP expression in BC tissues and cell lines is higher than that in the normal control group. The clinical analysis showed that IMUP is associated with lymph node metastasis and the outcome of neoadjuvant taxol-based therapy. The loss of function assay demonstrated that, with silencing IMUP, the capacities of proliferation, migration, and invasion of BC cell lines were impaired, while the apoptosis rate of cells increased. Meanwhile, the downregulation of IMUP could hinder the procession of epithelial-mesenchymal transition. Conclusion Our study proved that IMUP plays a vital role in BC and acts as a potential target and marker in future therapy.

The incidence of thyroid cancer remains high worldwide, and papillary thyroid cancer (PTC) is the most common type. Potassium Calcium-Activated Channel Subfamily N Member 4 (KCNN4) has been reported as an oncogene in various cancers. We examined expression of KCNN4 in public databases and discovered that it is upregulated in PTC. We verified this finding using our own validated cohort and RNA sequencing data. We also found that KCNN4 is a diagnostic and prognostic biomarker that is associated with disease-free survival, immune infiltration, and several other clinicopathological features of PTC. Gene Set Enrichment Analysis indicated that apoptotic and epithelial-mesenchymal transition gene sets are both upregulated in PTC patients with higher KCNN4 levels. In PTC cell lines, silencing KCNN4 inhibited cell proliferation, migration and invasion. Moreover, quantitative real-time PCR and Western blotting indicated that silencing KCNN4 increased expression of apoptotic genes in PTC cells and reduced the expression of genes involved in their epithelial-mesenchymal transition. These results suggest that KCNN4 promotes PTC progression by inducing epithelial-mesenchymal transition and suppressing apoptosis, which suggests KCNN4 may be a useful diagnostic and prognostic biomarker of PTC.

Conductive hydrogels (CHs) are a potential material for flexible electronics. However, most of CHs display disadvantages of low ionic conductivities and intolerance to low temperatures. Herein, a novel physical CHs with salt contents as high as 30 wt% was prepared with chitosan (CTS) and sodium alginate (SA) by combining the anti-polyelectrolyte effect and semi-dissolution acidification sol-gel transition (SD-A-SGT) method. The obtained hydrogels show extremely high ionic conductivities up to 2.96 × 10−1 S·cm−1 at room temperature and 4.9 × 10−2 S·cm−1 at −20 °C. The effects of different salts on the ion mobility and electrochemical properties of CTS/SA CHs were predicted and analyzed. The flexible supercapacitor assembled using CTS/SA CHs as the electrolyte exhibits the specific capacitance as high as 405 F·g−1 at the current density of 0.25 A·g−1 and satisfying electrochemical stability with 74.91% capacitance retention in 1000 cycles. Our work has provided a new strategy for constructing green CHs with high ionic conductivities.

Necroptosis, a key form of programmed lytic cell death, has gained recognition as an important driver in various inflammatory diseases. Inhibition of kinase activity of receptor interaction protein kinase 1 (RIPK1), which block the activation of the necroptosis pathway has shown therapeutic potential in many human diseases. In order to find new chemotypes of RIPK1 inhibitors, a virtual screening workflow was performed and led to the discovery of 8-benzoyl-3-benzyl-1,3,8-triazaspiro[4.5]decane-2,4-dione (compound 8) as a hit compound. Further structural optimization identified a series of 2,8-diazaspiro[4.5]decan-1-one derivatives as potent RIPK1 inhibitors. Among them, compound 41 exhibited prominent inhibitory activity against RIPK1 with an IC

In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.

Recently, the incidence of thyroid cancer is increasing worldwide. Papillary thyroid cancer (PTC) is the most common histological type of thyroid cancer. Whole‐transcriptome sequence analysis was performed to further understand the primary molecular mechanisms of the occurrence and progression of PTC. Results showed that Eva‐1 homolog A (EVA1A) may be a potential gene for the PTC‐associated gene in thyroid cancer. In this work, the role of EVA1A expression in thyroid cancer was investigated. Real‐time PCR was performed to detect the expression level of EVA1A in 43 pairs of PTC and four thyroid cancer cell lines. The Cancer Genome Atlas (TCGA) database was used to evaluate the relationship between the expression level of EVA1A and the pathological feature of PTC. The logistic regression analysis of the TCGA data set indicated that the expression of EVA1A was an independent risk factor for tumour, nde and metastasis (TNM) in PTC. This study shows the down‐regulation of EVA1A inhibited the colony formation, proliferation, migration and invasion of PTC cell lines. In the protein level, knockdown of EVA1A can regulate the expression of N‐cadherin, vimentin, Bcl‐xL, Bax, YAP and TAZ. This study indicated that EVA1A was an oncogene associated with PTC.

This study compared self-efficacy, job satisfaction and stress between Fujian and Taiwan teachers who are teaching in the application-oriented universities. Moreover, an attempt is made to explore the role of self-efficacy in this context. Participants consisted of 211 teachers from universities in Fujian (64%) and Taiwan (36%). Survey data shows that there is a distinct gap in the age structure between two groups of teachers in Fujian and Taiwan. T-tests show that Taiwanese teachers report higher self-efficacy beliefs than Fujian teachers, and Fujian teachers have higher job stress. Comparison among faculty members with different backgrounds in terms of the mechanism of application-oriented teaching troops is also discussed.

In the present work, a poly(γ-glutamic acid)/alginate/silver nanoparticle (PGA/Alg/AgNP) composite microsphere with excellent antibacterial and hemostatic properties was prepared by the in situ UV reduction and emulsion internal gelation method, and its potential application for antibacterial hemostatic dressing was explored. Well dispersed AgNPs were in situ synthesized by a UV reduction method with alginate as stabilizer and reductant. The AgNPs showed excellent antibacterial activities against both gram-negative and gram-positive bacteria. Additionally, the AgNPs prepared by the in-situ UV reduction exhibited better biocompatibility and antibacterial effects than those prepared by the conventional chemical reduction method. PGA/Alg/AgNP composite microspheres were then prepared with the AgNPs by an emulsion internal gelation method. Such microspheres were found to be a porous and hollow network with pH-sensitive swelling properties and excellent hemostatic performance, indicating its application potentials as an advanced antibacterial hemostatic material.

Cancer patients' cell free DNA (cfDNA) contains circulating tumor-derived DNA (ctDNA). The fast dynamic of clearance allows ctDNA to be used as biomarkers for tumor real time profiling. The benefit of non-invasive, cost effective, and easily-repetitive sampling makes liquid biopsy a highly-desirable option for molecular assessment. Deep sequencing has been widely used to investigate subpopulations in complex biological samples. However, there are still limitations of the sequencing technology due to the low yield of cfDNA amount, and errors introduced during sample preparation and sequencing. Approximately 1% of bases are incorrectly identified, depending on the specific platform and sequence context. Although Molecular Identifier can theoretically greatly reduce errors, it suffers from several drawbacks. First, it is difficult to synthesize double strand adapters with randomized Molecular Identifier. Second, due to the difficulty in making high quality Single Molecular Identifier (SMI) adaptors, the ligation efficiency might be compromised and therefore might require large amounts of input DNA. To optimize the liquid biopsy protocol, we first examined if there is any bias in the molecular barcodes' selection during library preparation. Indeed, a skewed trend with molecular barcode selection in ligation process has been detected. We also evaluated the error rates in molecular barcodes and found that there is a substantial amount of errors (~5% of total reads carrying the wrong molecular barcode). To overcome these issues, Omi-seq calculates Digital Molecular Identifier (DMI) using a pool of regular adapters with defined barcodes which can be easily synthesized in high quality. We then analyzed Horizon multiplex I cfDNA reference standard with the lowest available allele frequency (AF) 0.1%. With Omi-error correction, Omi-Seq was able to reproducibly detect the variants. We also evaluated Omi-Seq in real patient samples, Omi-Seq is able to detect variants at AF 0.03%. Omi-Seq was utilized to created cancer profiles for 202 subjects enrolled in The First Affiliated Hospital of Wenzhou Medical University breast cancer study. The gene landscape indicated that the most frequently detected genes are PIK3CA and TP53, followed by ERBB2. The accuracy of Her2 CNV in tissue/FFPE sample is 96% with 85 % sensitivity and 100% specificity. Mutation numbers vary between different molecular subtypes of cfDNA, where the basal-like group had more variants detected than Luminal patients. Furthermore, the ratio changes of max ctDNA AF (ctF) are highly correlated to the clinical response measurement, including cancer relapse, metastatic and treatment resistance. Our data show that ctDNA characterization with Omi-seq could extend the capacity of personalized cancer clinical management. Citation Format: Yinghao Wang, Yaoyao Guan, Jingjing Xiang, Lingguo Kong, Lizhi Lin, Judy Webb, Yunguang Tong, Ouchen Wang. Characterization of breast cancer ctDNA with Omi-Seq [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2489.

Chemical hydrogels have been extensively applied to the removal of heavy metal pollutants. However, most of chemical hydrogels inevitably contain toxic chemical crosslinker residues, which impose serious threats on the environment. Herein, a novel eco-friendly physically-crosslinked double-network hydrogel of chitosan/sodium alginate/calcium ion (CTS/SA/Ca2+ PCDNH) was prepared by the combination of the semi-dissolution acidification sol–gel transition method with the internal gelation method. The PCDNH is formed via the physical crosslinking of sustainable biopolymers, which avoids the excessive use of toxic chemical reagents. In addition, the PCDNH exhibits significantly better mechanical properties than the single-network physical hydrogel crosslinked via electrostatic interactions, which overcomes the weak mechanical properties of physical hydrogels. The formation mechanism and structure of the hydrogel were determined by Fourier-transform infrared spectroscopy (FTIR), 13C solid state nuclear magnetic resonance spectroscopy (13C-SSNMR) and scanning electron microscopy (SEM). The heavy metal ions adsorption mechanism was explored by X-ray photoelectron spectroscopy (XPS) analysis. The adsorption kinetics, isotherms and thermodynamics were further studied to understand the adsorption mechanism. Our work has provided a new method for the fabrication of natural polymers-based eco-friendly, low-cost and robust physical hydrogels for the heavy metal ions removal.

Luminal B HER-2-negative (LBHN) subtype is one of the major subtypes of breast cancer according to different features, clinical behaviors, and treatment response. The LBHN subtype shows a poor prognosis and is insensitive to endocrine therapy. Our work aim is to investigate the prognostic factor in the LBHN subgroup and, meanwhile, try to obtain an optimal prognostic index (PI) contrapose LBHN subgroup which helps to guide chemotherapy. A total of 515 female LBNH patients who underwent diagnosis and surgery at our hospitals from August 2008 to August 2018 were enrolled. Clinical–pathological information was obtained and immunohistochemistry result was available. From these cases, a 30% Ki-67 LI was employed to divide LBHN into two groups with low and high levels; high Ki-67 LI was associated with GIII tumor grade (P

In this work, we propose an analytical nonlinear model for laminate multiferroic composites in which the magnetic-field-induced strain in magnetostrictive phase is described by a standard square law taking the stress effect into account, whereas the ferroelectric phase retains a linear piezoelectric response. Furthermore, differing from previous models which assume uniform deformation, we take into account the stress attenuation and adopt non-uniform deformation along the layer thickness in both piezoelectric and magnetostrictive phases. Analysis of this model on L-T and L-L modes of sandwiched Terfenol-D/lead zirconate titanate/Terfenol-D composites can well reproduce the observed dc magnetic field (H(dc)) dependent magnetoelectric coefficients, which reach their maximum with the H(dc) all at about 500 Oe. The model also suggests that stress attenuation along the layer thickness in practical composites should be taken into account. Furthermore, the model also indicates that a high volume fraction of magnetostrictive phase is required to get giant magnetoelectric coupling, coinciding with existing models.

A one-dimensional pencil-like magnetoelectric (ME) sensor prototype is proposed which consists of a magnetostrictive cylinder, a truncated conical spacer, and a piezoelectric disk assembled in a rigid frame. By adopting the displacement-transfer mode in this sensor, not only the strain loss at the ME interface is avoided but also the volume fractions of both phases can be adjusted in a broader range. Using a nonlinear magnetostrictive model and linear piezoelectric model, the ME coupling performance of this sensor is systematically analyzed using lead titanate zirconate (PZT) disks and Terfenol-D cylinder as the components. Results show that such a sensor can practically exhibit giant quasi-static ME field coefficients (αE) and charge density coefficients (αD) as high as 455 V/cm Oe and 480×10−6 C/m2 Oe, which is about 10 times and 100 times higher than the best reported values, respectively. Furthermore, the ME coupling properties will decrease considerably when the stiffness of the frame is reduced. The...

Detecting the inside or buried defects in materials and structures is always a challenge in the field of nondestructive testing (NDT). In this paper, enlightened by the operation principle of the contact resonance force microscopy or atomic force acoustic microscopy (AFAM), we proposed a macroscopic NDT system based on contact resonance of the cantilever-sample surface to detect the local stiffness variations in materials or structures. We fabricated a piezoelectric unimorph with the dimension typically of 150 mm × 8 mm × 2 mm to act as a macroscopic cantilever, whose flexural mode vibration was driven by a wideband power amplifier together with a signal generator. The vibration signal of the macroscopic cantilever is detected by a high sensitive strain gauge bonded on the cantilever surface which is much more stable than the laser diode sensor in AFAM, thus making it very suitable for outdoor operations. Scanning is realized by a three-dimensional motorized stage with the Z axis for pressing force setting. The whole system is controlled by a LabVIEW-based homemade software. Like the AFAM, this NDT system can also work in two modes, i.e., the single-frequency mode and the resonance-tracking mode. In the latter mode, the contact stiffness at each pixel of the sample can be obtained by using the measured contact resonance frequency and a beam dynamics model. Testing results of this NDT system on a grid structure with an opaque panel show that in both modes the prefabricated defect beneath the panel can be detected and the grid structures can be clearly "seen," which indicates the validity of this NDT system. The sensitivity of this NDT system was also examined.