Highly Strong, Tough, and Cryogenically Adaptive Hydrogel Ionic Conductors via Coordination Interactions.

Despite the promise of high flexibility and conformability of hydrogel ionic conductors, existing polymeric conductive hydrogels have long suffered from compromises in mechanical, electrical, and cryoadaptive properties due to monotonous functional improvement strategies, leading to lingering challenges. Here, we propose an all-in-one strategy for the preparation of poly(acrylic acid)/cellulose (PAA/Cel) hydrogel ionic conductors in a facile yet effective manner combining acrylic acid and salt-dissolved cellulose, in which abundant zinc ions simultaneously form strong coordination interactions with the two polymers, while free solute salts contribute to ionic conductivity and bind water molecules to prevent freezing. Therefore, the developed PAA/Cel hydrogel simultaneously achieved excellent mechanical, conductive, and cryogenically adaptive properties, with performances of 42.5 MPa for compressive strength, 1.6 MPa for tensile strength, 896.9% for stretchability, 9.2 MJ m-3 for toughness, 59.5 kJ m-2 for fracture energy, and 13.9 and 6.2 mS cm-1 for ionic conductivity at 25 and -70 °C, respectively. Enabled by these features, the resultant hydrogel ionic conductor is further demonstrated to be assembled as a self-powered electronic skin (e-skin) with high signal-to-noise ratio for use in monitoring movement and physiological signals regardless of cold temperatures, with hinting that could go beyond high-performance hydrogel ionic conductors.

Strong and tough poly(vinyl alcohol)/xanthan gum-based ionic conducting hydrogel enabled through the synergistic effect of ion cross-linking and salting out.

The mechanical properties of ionic conductive hydrogels (ICHs) are generally inadequate, leading to their susceptibility to breakage under external forces and consequently resulting in the failure of flexible electronic devices. In this work, a simple and convenient strategy was proposed based on the synergistic effect of ion cross-linking and salting out, in which the hydrogels consisting of polyvinyl alcohol (PVA) and xanthan gum (XG) were immersed in zinc sulfate (ZnSO4) solution to obtain ICHs with exceptional mechanical properties. The salt-out effects between PVA chains and SO42- ions along with the cross-linked network of XG chains and Zn2+ ions contribute to the desirable mechanical properties of ICHs. Notably, the mechanical properties of ICHs can be adjusted by changing the concentration of ZnSO4 solution. Consequently, the optimum fracture stress and the fracture energy can reach 3.38 MPa and 12.13 KJ m-2, respectively. Moreover, the ICHs demonstrated a favorable sensitivity (up to 2.05) when utilized as a strain sensor, exhibiting an accurate detection of human body movements across various amplitudes.

Temperature-Mediated Phase Separation Enables Strong yet Reversible Mechanical and Adhesive Hydrogels.

Hydrogels with strong yet reversible mechanical and adhesive properties fabricated in a facile and friendly manner are important for engineering and intelligent electronics applications but are challenging to create and control. Existing approaches for preparing hydrogels involve complicated pretreatments and produce hydrogels that suffer from limited skin applicability. Copolymerized hydrogels are expected to present an intriguing target in this field by means of thermoresponsive features, while the perceived intrinsic flaws of brittleness, easy fracture, and weak adhesion enervate the development prospects. Herein, we report a hydrogel with strong yet reversible mechanical and adhesive properties using cellulose nanofibrils to simultaneously address multiple dilemmas inspired by a temperature-mediated phase separation strategy. This strategy applies temperature-driven formation and dissociation of hydrogen bonds between common copolymers and cellulose nanofibrils to trigger the onset and termination of phase separation for dynamically reversible on-demand properties. The resulting hydrogel exhibits up to 96.0% (117.2 J/m2 vs 4.8 J/m2 for interfacial toughness) and 85.7% (0.02 MPa vs 0.14 MPa for mechanical stiffness) adhesive and mechanical tunability when worked on skin, respectively. Our strategy offers a promising, simple, and efficient way to directly achieve robust adhesion performance in one step using common copolymers and biomass resources, with implications that could go beyond strong yet adhesive hydrogels.

A sweat-pH-enabled strongly adhesive hydrogel for self-powered e-skin applications.

On-skin hydrogel electrodes are poorly conformable in sweaty scenarios due to low electrode-skin adhesion resulting from the sweat film formed on the skin surface, which seriously hinders practical applications. In this study, we fabricated a tough adhesive cellulose-nanofibril/poly(acrylic acid) (CNF/PAA) hydrogel with tight hydrogen-bond (H-bond) networks based on a common monomer and a biomass resource. Furthermore, inherent H-bonded network structures can be disrupted through judicious engineering using excess hydronium ions produced through sweating, which facilitate the transition to protonation and modulate the release of active groups (i.e., hydroxyl and carboxyl groups) accompanied by a pH drop. The lower pH enhances adhesive performance, especially on skin, with a 9.7-fold higher interfacial toughness (453.47 vs. 46.74 J m-2), an 8.6-fold higher shear strength (600.14 vs. 69.71 kPa), and a 10.4-fold higher tensile strength (556.44 vs. 53.67 kPa) observed at pH 4.5 compared to the corresponding values at pH 7.5. Our prepared hydrogel electrode remains conformable on sweaty skin when assembled as a self-powered electronic skin (e-skin) and enables electrophysiological signals to be reliably collected with high signal-to-noise ratios when exercising. The strategy presented here promotes the design of high-performance adhesive hydrogels that may serve to record continuous electrophysiological signals under real-life conditions (beyond sweating) for various intelligent monitoring systems.

Survey of risk factors contributed to lymphatic metastasis in patients with oral tongue cancer by immunohistochemistry.

OBJECTIVES: The aim of this study was to define the biomarkers of lymphatic spread which facilitate the appropriate therapy for oral tongue squamous cell carcinoma (OTSCC) patients at early stage. Here, we investigated the expression levels of seven biomarkers in oral squamous cell carcinoma (OSCC) tissues as well as their associations with the clinicopathologic features of OTSCC patients. METHODS: The OTSCC samples were obtained from 138 patients undergoing tumor resection. Immunohistochemical staining was performed by using ColIA, ColIVA, Fn1, MMP-1, MMP-2, uPA, and D2-40 antibodies. Expression level of theses biomarkers in normal and tumor tissues were compared. Risk factors of lymphatic dissemination were evaluated by logistic regression equation. RESULTS: LVD, MMP-1, MMP-2, and uPA in cancer tissues were significantly higher than those in normal tissue, and ColIA, ColIVA, and Fn1 in cancer tissue were significantly lower than those in normal tissue. Similar results were obtained from the comparison between metastatic tumor and non-metastatic tumor. All biomarker expressions were closely related with lymph node status and clinical stage. Additionally, the regression equation demonstrated that LVD is the risk factor of lymphatic metastasis in OTSCC patients (OR = 1.732; 95% CIs: 1.167-2.057; P < 0.05). CONCLUSIONS: Down-regulation of ColIA, ColIVA, and Fn1 and up-regulation of LVD, MMP-1, MMP-2, and uPA might be important features of OSCC progression, which may exert their functions and favorably predict lymphatic dissemination for OSCC patients at relatively early stage. Among these biomarkers, increased LVD is an independent risk factor of lymphatic metastasis, which could better predict whether metastasis will occur or not.

Expression of angiopoietin-like 4 and tenascin C but not cathepsin C mRNA predicts prognosis of oral tongue squamous cell carcinoma.

Analysis of gene expression using RNA from the paraffin-embedded tissues is becoming an important way to study cancer pathogenesis. In this article, total RNA was extracted from tissue of 158 cases of paraffin-embedded tongue cancer, and expression of angiopoietin-like 4, tenascin-C and cathepsin-C were detected by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Our results demonstrated that high expression level of angiopoietin-like 4 or tenascin-C was predictive of poor prognosis of tongue cancer patients (p = 0.024 and p = 0.011, respectively), especially when expression levels of both genes were concomitantly high (p = 0.001). Additionally, high expression of angiopoietin-like 4 and tenascin-C, or concomitant high expression of angiopoietin-like 4 and tenascin-C were independent prognostic factors of poor survival in patients with tongue cancer. These results suggest that the improved method of RNA extraction is suitable for analysing gene expression of paraffin-embedded solid tumours. Angiopoietin-like and tenascin-C, especially the combination of angiopoietin-like 4 and tenascin-C, are useful for predicting the prognosis of the patients with tongue cancer, independent of lymph node metastasis status.

Application of RT-PCR in formalin-fixed and paraffin-embedded lung cancer tissues.

AIM: To analyze gene expression in formalin-fixed, paraffin-embedded lung cancer tissues using modified method. METHODS: Total RNA from frozen tissues was extracted using TRIZOL reagent. RNA was extracted from formalin-fixed, paraffin-embedded tissues by digestion with proteinase K before the acid-phenol:chloroform extraction and carrier precipitation. We modified this method by using a higher concentration of proteinase K and a longer digestion time, optimized to 16 hours. RT-PCR and real-time RT-PCR were used to check reproducibility and the concordance between frozen and paraffin-embedded samples. RESULTS: The results showed that the RNA extracted from the paraffin-embedded lung tissues had high quality with the most fragment length between 28S and 18S bands (about 1000 to 2000 bases). The housekeeping gene GUSB exhibited low variation of expression in frozen and paraffin-embedded lung tissues, whereas PGK1 had the lowest variation in lymphoma tissues. Furthermore, real-time PCR analysis of the expression of known prognostic genes in non-small cell lung carcinoma (NSCLC) demonstrated an extremely high correlation (r>0.880) between the paired frozen and formalin-fixed, paraffin-embedded specimens. CONCLUSION: This improved method of RNA extraction is suitable for real-time quantitative RT-PCR, and may be used for global gene expression profiling of paraffin-embedded tissues.

Gene expression levels of CSNK1A1 and AAC-11, but not NME1, in tumor tissues as prognostic factors in NSCLC patients.

BACKGROUND: To analyze the prognostic significance of the genes casein kinase 2 alpha subunit (CSNK2A1), anti-apoptosis clone-11 (AAC-11), and tumor metastasis suppressor NME1 in completely resected non-small cell lung cancer (NSCLC) patients. MATERIAL/METHODS: Total RNA was extracted from 145 cases of completely resected, formalin-fixed, paraffin-embedded NSCLC tissues. mRNA expression levels of CSNK2A1, AAC-11, and NME1 were detected by real-time reverse-transcriptase polymerase chain reaction. Univariate and multivariate survival analyses were used to identify factors related to prognosis. RESULTS: A correlation between CSNK2A1 and AAC-11 mRNA expression levels (rs=0.366, p=0.000) was found. Univariate analysis showed that high expression of CSNK2A1 and AAC-11 was predictive of poor prognosis in NSCLC patients (p=0.029 and 0.044, respectively), especially when expression levels of both genes were concomitantly high (p=0.007). Multivariate Cox regression analysis showed that high expression of CSNK2A1, or concomitantly high expression of CSNK2A1 and AAC-11, are independent prognostic factors of poor survival in NSCLC patients. However, NME1 mRNA expression level did not significantly influence survival in NSCLC patients. CONCLUSIONS: This retrospective study indicates that CSNK2A1 and AAC-11, especially in combination, are useful prognosis markers in NSCLC patients after complete resection, independent of lymph node metastasis status.

Different BAG-1 isoforms have distinct functions in modulating chemotherapeutic-induced apoptosis in breast cancer cells.

AIM: BAG-1 is a multifunctional anti-apoptotic gene with four isoforms, and different BAG-1 isoforms have different anti-apoptotic functions. In this study, we transfected BAG-1 isoforms into the human breast cancer cell lines Hs578T (ER negative) and MCF-7 (ER positive) to study their effect on apoptosis with or without estrogens. METHODS: The constructed recombinant expression vectors carrying individual BAG-1 isoforms was used to transfect human breast cancer cell lines Hs578T (ER negative) and MCF-7 (ER positive). After stable cell lines were made, a variety of apoptosis-inducing agents, including doxorubicin, docetaxel, and 5-FU, was used to treat these cell lines with or without estrogen to test the role of BAG-1. The mechanism by which BAG-1 affected the function of Bcl-2 was exploredby using the cycloheximide chase assay. RESULTS: The BAG-1 p50 and p46 isoforms significantly enhanced the resistance to apoptosis in both cell lines according to flow cytometry analysis. BAG-1 p33 and p29 failed to protect the transfected cells from apoptosis. The cell viability assay showed that only BAG-1 p50, but not p46, p33, or p29, increased estrogen-dependent function in ER-positive cell line MCF-7. Only BAG-1 p50 dramatically increased its anti-apoptotic ability in the presence of estrogen, while estrogen has very little effect on the anti-apoptotic ability of other BAG-1 isoforms. In the detection of the expression of K-ras, Hsp70, cytochrome c, Raf-1, ER-alpha, and Bcl-2 in MCF-7 cells by Western blot, only Bcl-2 protein expression was significantly increased in MCF-7 cells transfected with BAG-1 p50 and p46, respectively. Furthermore, the cycloheximide chase assay indicated that the degradation of Bcl-2 protein was extended in the BAG-1 p50 and p46 transfected MCF-7 cells. CONCLUSION: Distinct isoforms of BAG-1 have different anti-apoptotic functions in breast cancer cells, and that the BAG-1 p50 isoform can potentiate the role of estrogen in ER-positive breast cancer.

Alteration in gene expression profile and biological behavior in human lung cancer cell line NL9980 by nm23-H1 gene silencing.

Lung cancer is the leading cause of cancer death in both men and women. Tumor metastasis is an essential aspect of lung cancer progression. nm23-H1 is a metastasis suppressor gene. The molecular mechanism by which nm23-H1 suppresses the metastasis is still unclear. Here, we compared the gene expression profile of human large cell lung cancer cell line NL9980 by nm23-H1 gene silencing with that of negative control cells to comprehensively investigate nm23-H1-mediated changes in gene expression of NL9980 cells. Microarray assay revealed that expression of 733-known genes (1.9%, 733/38,500) were altered in response to nm23-H1 gene silencing, including 466 upregulated genes and 267 downregulated. real-time PCR assay of the expression changes indicated that 81.82% (45/55) of verified genes were consistent with that observed in microarray assay. The upregulated genes included MMP-1, -2, SNAI2, CXCL1, 2, 3, PAI-2, while the downregulated genes included cystatin B, TIMP-2, E-cadherin, centrin-2, all of which have been associated with tumor metastasis. Furthermore, we confirmed by Western blot that the expression of MMP-1 and -2 were significantly increased while that of cystatin B was dramatically decreased in NL9980-nm23-H1 silencing cells. The NL9980-nm23-H1 silencing cells exhibited significantly more S phase growth and invasive ability. Thus, silencing of nm23-H1 gene caused metastasis-related gene expression changes in lung cancer cells. The knockdown of nm23-H1 expression may change the lung cancer cells to a more invasive phenotype through alteration in the expression of a set of genes.

Wastewater discharge impact on drinking water sources along the Yangtze River (China).

Unplanned indirect (de facto) wastewater reuse occurs when wastewater is discharged into surface waters upstream of potable drinking water treatment plant intakes. This paper aims to predict percentages and trends of de facto reuse throughout the Yangtze River watershed in order to understand the relative contribution of wastewater discharges into the river and its tributaries towards averting water scarcity concerns. The Yangtze River is the third longest in the world and supports more than 1/15 of the world's population, yet the importance of wastewater on the river remains ill-defined. Municipal wastewater produced in the Yangtze River Basin increased by 41% between 1998 and 2014, from 2580m3/s to 3646m3/s. Under low flow conditions in the Yangtze River near Shanghai, treated wastewater contributions to river flows increased from 8% in 1998 to 14% in 2014. The highest levels of de facto reuse appeared along a major tributary (Han River) of the Yangtze River, where de facto reuse can exceed 20%. While this initial analysis of de facto reuse used water supply and wastewater data from 110 cities in the basin and 11 gauging stations with >50years of historic streamflow data, the outcome was limited by the lack of gauging stations at more locations (i.e., data had to be predicted using digital elevation mapping) and lack of precise geospatial location of drinking water intakes or wastewater discharges. This limited the predictive capability of the model relative to larger datasets available in other countries (e.g., USA). This assessment is the first analysis of de facto wastewater reuse in the Yangtze River Basin. It will help identify sections of the river at higher risk for wastewater-related pollutants due to presence of-and reliance on-wastewater discharge that could be the focus of field studies and model predictions of higher spatial and temporal resolution.

[The expression of BAG-1 and its clinical significance in human lung cancer.].

BACKGROUND: BAG-1 is a multifunctional anti-apoptotic protein that binds to a variety of cellular proteins and affects their functions. It has been proven that overexpression of BAG-1 was observed in a number of human maligancies and correlated with their prognosis. The aim of this study is to determine BAG-1 mRNA expression in human lung cancer tissues and its clinical significance. METHODS: The expression of BAG-1 was detected by real-time PCR in formalin-fixed, paraffin-embedded human lung cancer tissues of 156 cases. RESULTS: (1) The median survival time (MST, 33.5 months) in BAG-1 low-expression group was significantly higher than that (20.5 months) in BAG-1 highexpression group (P <0.005); (2) The 3-year and 5-year survival rates (44.74%; 26.32%) in BAG-1 low-expression group were dramatically higher than that in BAG-1 high-expression group (32.5%; 21.25%)(P <0.05), respectively. The survival curves in BAG-1 low-expression group was also significantly better than that in BAG-1 high-expression group (P =0.045); (3) The further analysis indicated that the survical curves in BAG-1 low-expression group were much better than that in BAG-1 high-expression group in the lung cancer patient with TNM stage I, or with squamous cell cacrinoma, or without any metastasis, respectively (P <0.05). CONCLUSIONS: BAG-1 may be a biomarker for the prognosis of lung cancer patients, especially for the lung cancer patients with stage I or squamous cell carcinoma.

[Construction and expression of eukaryotic expression vectors of full-length, amino-terminus and carboxyl-terminus Raf gene.].

BACKGROUND: Raf is a key molecule in the Ras-Raf-MEK-ERK signal transduction pathway and is highly activated in different human carcinomas. However, its biological functions and regulation mechanisms are still unclear. The aims of this study were to construct eukaryotic expression vectors with Raf full encoding region, truncated amino-terminus and carboxyl-terminus, respectively. METHODS: Eukaryotic expression vectors of pCMV-Tag2b-Raf-1, pCMV-Tag2b-N-Raf and pCMV-Tag2b-C-Raf were constructed by gene recombination technique and confirmed by restriction enzyme analysis and DNA sequencing. Furthermore, the expression of these fusion proteins was detected by western blot in transient transfected 293T cells. RESULTS: The sequences and open reading frames of these three vectors were completely consistent with experimental design. All target proteins can be detected in 293T cells. CONCLUSIONS: Eukaryotic expression vectors of pCMV-Tag2b-Raf-1, pCMV-Tag2b-N-Raf and pCMV-Tag2b-CRaf were successfully constructed and can be expressed in 293T cells.