Thermochromic Hydrogels with Opaque-Transparent Gradient Transition for Switchable Window and Temperature Monitor.

In recent years, the thermochromic hydrogel was acted as suitable sandwiching material to adjust light transmission. However, to accurately control the thermochromic temperature in a wide range still was a significant challenge. Here, a simple method was explored to prepare hydrogels with gradient opaque-transparent transition thermochromic temperature from 5 °C to 53 °C, which was regulated by the aggregation state of sodium dodecyl sulfate micelles by adding potassium tartrate hemihydrate and cations. Using Li+ , Na+ , and K+ as cations, the accuracy was controlled at 1 °C. Moreover, the transmittance of the hydrogel was not changed when the thermochromic temperature was adjusted. As a result, an intelligent window was fabricated by utilizing thermochromic hydrogel as a sandwiching layer into the outer glass layers, which could effectively and stably regulate the visible and infrared light. The temperature monitors/detectors were also designed, which showed excellent temperature monitoring/detecting ability. Therefore, this low-cost, high-efficient, large-scale prepared thermochromic hydrogel provided more potential for intelligent temperature devices.

Hierarchical Porous Aerogels With Multiple Adsorptive Interactions for Dye Wastewater Purification.

Aerogels present a huge potential for removing organic dyes from printing and dyeing wastewater (PDW). However, the preparation of aerogels with multiple dye adsorption capabilities remains a challenge, as many existing aerogels are limited to adsorbing only a single type of dye. Herein, a composite aerogel (CG/T-rGO) with the addition of carboxymethyl chitosan, gelatin and tannic acid reduced graphene oxide (T-rGO) was synthesized by freeze-drying technology. The electrostatic interactions between dye molecular and GEL/CMCS (CG) networks, as well as the supramolecular interactions (H-bonds, electrostatic interactions and π-π stacks) between T-rGO, have endowed the aerogel with the ability to adsorb multiple types of dye, such as methylene blue (MB) and methyl orange (MO). Results exhibited that the prepared CG/T-rGO aerogel possessed strong mechanical strength and a porous 3D network structure with a porosity of 96.33 %. Using MB and MO as adsorbates, the adsorption capacity (88.2 mg/g and 66.6 mg/g, respectively) and the mechanism of the CG/T-rGO aerogel were investigated. The adsorption processes of aerogel for MB and MO were shown to follow the pseudo-second-order kinetic model and Langmuir isotherm model, indicating the chemical adsorption of a monolayer. The proposed aerogel in this work has promising prospects for dye removal from PDW.

Special issue "The advance of solid tumor research in China": FGFR4 alterations predict efficacy of immune checkpoint inhibitors in nonsmall cell lung cancer.

Immune checkpoint inhibitors (ICIs), which represent the new standard of care for advanced nonsmall cell lung cancer (NCSLC), are not effective in many patients. Biomarkers are needed to guide treatment. Sequencing data of an ICI-treated cohort were analyzed to identify genomic signatures predicting ICI efficacy, followed by validation using multiple independent cohorts. Their predictive mechanism was explored by evaluating the tumor immune microenvironment and tumor mutational burden (TMB). In the discovery cohort, patients carrying FGFR4 alterations (FGFR4altered ) had a better objective response rate (ORR) (50.0% vs 19.4%; P = .057) and improved median progression-free survival (mPFS) (13.17 vs 3.17 months; HR 0.37; 95% CI 0.14-1; P = .04) than wild-type patients (FGFR4wt ). In the publicly available validation cohorts, FGFR4 alterations correlated with higher ORR (100% vs 31%; P = .028), longer median overall survival (mOS) (not reached [NR] vs 11 months; HR 0.28, 95% CI 0.09-0.89, P = .02), and mPFS (NR vs 6.07 months; HR 0.05, 95% CI 0-3.94, P = .039). FGFR4 alterations were confirmed as an independent predictor of superior PFS (P = .014) and OS (P = .005). FGFR4altered patients also exhibited a significantly improved disease control rate (100% vs 60%, P = .045) and prolonged mPFS (9.70 vs 3.16 months; P = .095) compared to FGFR4wt patients in our Shanghai Pulmonary Hospital cohort. FGFR4 alterations associated with a higher TMB levels, more CD8+ T cells in the tumor stroma, and a higher M1/M2 ratio for tumor-associated macrophages in the tumor center and stroma. Thus, FGFR4 alterations may serve as a potential independent predictor of ICI efficacy in NSCLC.

ICI plus chemotherapy prolonged survival over ICI alone in patients with previously treated advanced NSCLC.

OBJECTIVES: Immune checkpoint inhibitors (ICI) monotherapy was standard of care in second-line treatment of patients with advance non-small cell lung cancer (NSCLC). This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC. PATIENTS AND METHODS: An investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator. RESULTS: From April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treated with ICI monotherapy were selected as a comparator. ICI plus chemotherapy showed a significantly higher ORR (35.5% vs. 15.7%, p=0.039), prolonged PFS (median: 5.6 vs. 2.5 months, p = 0.013) and OS (median: NE vs. 12.6 months, p = 0.038) compared with ICI alone. In the subgroup of negative PD-L1 expression (9 patients in combination group and 12 patients in monotherapy group), ICI plus chemotherapy also had a favorable ORR (44.4% vs. 8.3%, p = 0.119), longer PFS (median: 6.5 vs 3.0 months, p < 0.05) and OS (median: NE vs. 8.2 months, p = 0.117). Meanwhile, the addition of chemotherapy did not increase immune-related adverse events. CONCLUSIONS: ICI plus chemotherapy showed superior ORR, PFS and OS than ICI alone patients with previous treated advanced NSCLC. These findings warrant further investigation.

Increased blood-based intratumor heterogeneity (bITH) is associated with unfavorable outcomes of immune checkpoint inhibitors plus chemotherapy in non-small cell lung cancer.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has been the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with driver-gene negative. However, efficacy biomarkers for ICIs-based combination therapy are lacking. We aimed to identify potential factors associated with outcomes of ICIs plus chemotherapy at baseline and dynamic changes in peripheral blood. METHODS: We collected plasma samples of 51 advanced NSCLC patients without EGFR/ALK/ROS1 alteration at baseline and/or after two treatment cycles of ICIs plus chemotherapy. A blood-based intratumor heterogeneity (bITH) score was calculated based on the allele frequencies of somatic mutations using a 520-gene panel. bITH-up was defined as a ≥ 10% increase in bITH score from baseline, with a second confirmatory measurement after treatment. RESULTS: At baseline, the number of metastatic organs and lung immune prognostic index (LIPI) were significantly associated with shorter progression-free survival (PFS) of ICIs plus chemotherapy, while bITH and other common molecular biomarkers, including ctDNA level, blood-based tumor mutational burden (bTMB), and PD-L1 expression, had no effect on PFS. LRP1B mutation at baseline was significantly associated with favorable outcomes to ICIs plus chemotherapy. There were 37 patients who had paired samples at baseline and after two cycles of treatment, with the median interval of 53 days. Intriguingly, patients with bITH-up had significant shorter PFS (HR, 4.92; 95% CI, 1.72-14.07; P = 0.001) and a lower durable clinical benefit rate (0 vs 41.38%, P = 0.036) than those with bITH-stable or down. Case studies indicated that bITH was promising to predict disease progression. CONCLUSIONS: The present study is the first to report that increased bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.

Tough and self-healing hydrogels based on transient crosslinking by nanoparticles.

In this investigation, transient crosslinking was constructed to obtain a hydrogel with excellent mechanical and self-healing properties. Firstly, core-shell particles with hydrophilic amino groups were prepared by emulsion polymerization and subsequently dispersed into hydrophobic association polyacrylamide hydrogels. Transient crosslinking was constructed through hydrogen bonding between core-shell particles and polyacrylamide. As a result, the hydrogels exhibited a tensile strength of 1.4 MPa and self-healing efficiency of 98% at 24 h. Furthermore, reconstruction of the transient crosslinking was confirmed from rheological measurements. Therefore, the essential reinforcement principle based on transient crosslinking would open a novel strategy to obtain hydrogels with superior toughness and self-healing properties.

Nucleotide-Tackified Organohydrogel Electrolyte for Environmentally Self-Adaptive Flexible Supercapacitor with Robust Electrolyte/Electrode Interface.

Hydrogel electrolytes have attracted enormous attention in flexible and safe supercapacitors. However, the interfacial contact problem between hydrogel electrolyte and electrodes, and the environmental instability are the key factors restricting the development of hydrogel-based supercapacitors. Here, a nucleotide-tackified adhesive organohydrogel electrolyte is successfully constructed and exhibits freezing resistance and water-holding ability based on the water/glycerol binary solvent system. Adenosine monophosphate enables the organohydrogels to possess outstanding adhesion and mechanical robustness. The robust adhesion can ensure close contact between the organohydrogel electrolyte and electrodes for constructing an all-in-one supercapacitor with low interfacial contact resistance. Impressively, the integrated organohydrogel-based supercapacitors display an areal specific capacitance of 163.6 mF cm-2 . Besides, the supercapacitors feature prominent environmental stability with capacitance retention of 90.6% after 5000 charging/discharging cycles at -20 °C. Furthermore, based on the strong interfacial adhesion, the supercapacitors present excellent electrochemical stability without delamination/displacement between electrolyte and electrodes even under severe deformations such as bending and twisting. It is anticipated that this work will provide an encouraging way for developing flexible energy storage devices with electrochemical stability and environmental adaptability.

Exosomes transmit T790M mutation-induced resistance in EGFR-mutant NSCLC by activating PI3K/AKT signalling pathway.

Emerging evidence has shown that exosomes derived from drug-resistant tumour cells are able to horizontally transmit drug-resistant phenotype to sensitive cells. However, whether exosomes shed by EGFR T790M-mutant-resistant NSCLC cells could transfer drug resistance to sensitive cells has not been investigated. We isolated exosomes from the conditioned medium (CM) of T790M-mutant NSCLC cell line H1975 and sensitive cell line PC9. The role and mechanism of exosomes in regulating gefitinib resistance was investigated both in vitro and in vivo. Exosome-derived miRNA expression profiles from PC9 and H1975 were analysed by small RNA sequencing and confirmed by qRT-PCR. We found that exosomes shed by H1975 could transfer gefitinib resistance to PC9 both in vitro and in vivo through activating PI3K/AKT signalling pathway. Small RNA sequencing and RT-PCR confirmed that miR-3648 and miR-522-3p were the two most differentially expressed miRNAs and functional study showed that up-regulation of miR-522-3p could induce gefitinib resistance in PC9 cell. The findings of our study reveal an important mechanism of acquired resistance to EGFR-TKIs in NSCLC.

EGFR-TKIs plus local therapy demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases.

To investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (LM). Patients with EGFR-mutant NSCLC and oligometastatic or oligoprogressive LM who met inclusion criteria were retrospectively identified. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and patterns of failure. Addition of local therapy was associated with a significantly longer PFS (13.8 vs. 8.6 m, p <0.001) and OS (31.2 vs. 18.5 m, p <0.001) in whole group. In oligometastatic cohort, 20 patients received EGFR-TKIs and 23 received EGFR-TKIs plus local therapy as first-line treatment. Addition of local therapy showed a significantly longer PFS (12.9 vs. 7.9 m, p = 0.041) and OS (36.8 vs. 21.3 m, p = 0.034) than EGFR-TKIs alone. In oligoprogressive cohort, 24 patients received continuation of EGFR-TKIs plus local therapy and 25 received switching chemotherapy. Median PFS2 (13.9 vs. 9.2 m, p = 0.007) and OS (28.3 vs. 17.1 m, p = 0.011) was significantly longer in combined group than in switching chemotherapy group. Distant metastatic sites progression was the major pattern of failure in combined group while locoregional recurrence was the major reason in monotherapy or switching chemotherapy group. Our study suggested that EGFR-TKIs plus local therapy showed prolonged survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive LM, indicating addition of local therapy would be alternative choice in this clinical scenario.

Robust and anti-fatigue hydrophobic association hydrogels assisted by titanium dioxide for photocatalytic activity.

Currently, robust and functional hydrogels have attracted extensive attention due to their potential applications in wastewater treatment, farmland water conservation and other fields. Herein, a series of hydrophobic association hydrogels assisted by titanium dioxide (TiO2) was fabricated via one-pot in situ photo-induced polymerization. TiO2 nanoparticles could act as both photo-initiators and physical crosslinking points. The TiO2-assisted hydrophobic association hydrogels exhibited a high tensile strength of 306 kPa, superior compression strength of 2.17 MPa and excellent fatigue resistance. Simultaneously, the incorporation of TiO2 endowed the hydrogel with photocatalytic capacity for dye wastewater treatment based on the inherent nature of TiO2. The results indicated that the hydrogels contributed to the degradation of various ionic dyes including methylene blue, rhodamine B and bromophenol blue, and the removal of methylene blue achieved a rate of 96.63%. Significantly, the hydrogel could be repeatedly utilized and the removal rate showed no evident decrease after five cycles, indicating that the hydrogels could be powerful candidates as photocatalysts for dye wastewater treatment.

[Chemical profiling from water extract of Wikstroemia indica by UPLC-Q-TOF-MS/MS].

In this study,a method using ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) was established to identify complicated chemical constituents of Wikstroemia indica. Chromatographic separation was performed on an AcclaimTMRSLC 120-C18 column( 2. 1 mm×100 mm,2. 2 µm) using gradient elution with 0. 2% ammonium formate buffer salt solution( A)-0. 2% ammonium formate buffer salt solution methanol( B) as mobile phase. The column temperature was maintained at 30 ℃. The analytes were determined by positive and negative ion modes with electro-spray ionization source. A total of 52 compounds( including eleven coumarins,thirteen flavonoids,ten lignans,two amides,four phenolic acids,six sesquiterpenes and six other compounds) were identified or tentatively characterized from the water extract of W. indica by comparing their retention times and MS spectra with those of authentic standards or literature datas. Three compounds were found for the first time from W.indica namely isomer of indicanone,ß-hydroxypropiovanillone and epiprocurcumenol. Furthermore,the fragmentation rules of some compounds were speculated and summarized. In addition,the cleavage pathways of guaiane sesquiterpenes were described for the first time,which can provide reference for studying the fragmentation pathways of similar compounds. This study provides an easy way to identify chemical constituents of traditional Chinese medicine and a basis for the further study on chemical fundamentals of W. indica.

[Mechanism research of curcumin on cancer cells based on cell metabolic profiling].

In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.

Pretreatment neutrophil-to-lymphocyte ratio is associated with outcome of advanced-stage cancer patients treated with immunotherapy: a meta-analysis.

BACKGROUND: To investigate the association between pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes for advanced-stage cancer patients treated with immunotherapy. METHODS: We conducted a comprehensive literature search to assess the relationship between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in advanced-stage cancer patients treated with immunotherapy. Published data including hazard ratios (HRs) and related 95% confidence interval (CI) were extracted. Pooled estimates of treatment outcomes were calculated using RevMan 5.3.5. RESULTS: Twenty-seven studies with 4647 patients were included in the current study. The pooled results suggested that high pretreatment blood NLR was correlated with significant shorter OS (HR = 1.98, 95% CI 1.66-2.36, P < 0.001) and PFS (HR = 1.78, 95% CI 1.48-2.15, P < 0.001). Subgroup analysis stratified by study targets revealed that anti-VEGF/VEGFR therapy (HR = 2.04, 95% CI 1.61-2.60, P < 0.001) and immune checkpoints blockade (HR = 2.16, 95% CI 1.86-2.51, P < 0.001) were significantly associated with inferior OS while other targets (HR = 1.63, 95% CI 0.89-2.99, P = 0.120) were not associated with OS. There was no correlation between distinct NLR cutoff values and OS ([Formula: see text] = 0.218, P = 0.329) or PFS benefit ([Formula: see text] = - 0.386, P = 0.140). Of note, HRs of PFS showed significant correlation with HRs of OS ([Formula: see text] = 0.656, P = 0.015). CONCLUSION: Elevated pretreatment blood NLR was a promising prognostic and predictive biomarker for advanced-stage cancer patients treated with immunotherapy.

Multipurpose and Durable Adhesive Hydrogel Assisted by Adenine and Uracil from Ribonucleic Acid.

Nucleobase pairs of adenine and uracil (A-U) from ribonucleic acid are of particular interest for various promising material properties. Herein, a novel polyacrylamide hydrogel with adhesive properties that are assisted by adenine and uracil has been designed and investigated. The incorporation of adenine and uracil enables the formation of a polyacrylamide hydrogel with remarkable adhesive behaviour with various materials including polytetrafluoroethylene (PTFE), plastics, rubber, glasses, metal, ceramics and wood. Moreover, the adhesive hydrogel can easily and directly adhere to humid biological tissues without any extra process, including heart, liver, spleen, lung, kidney, bone and muscle of mouse. More impressively, even after repeated peeling tests (10×), the AU-mediated polyacrylamide hydrogel still exhibits excellent durable adhesion for various materials. From mechanical contact tests, the adhesion energy of the A-U adhesive hydrogel is 47.9 J m-2 , which is nearly nine times that of polyacrylamide hydrogel (5.3 J m-2 ). The 90° peeling strength for aluminium, titanium, silica rubbers, glasses, PTFE and hogskin is 518, 645, 445, 396, 349, and 119 N m-1 , respectively. The multipurpose and durable adhesive behaviour of hydrogels assisted by adenine and uracil indicated the promise of nucleobase pairs from ribonucleic acid for the future development of adhesive materials.

Frequency of the acquired resistant mutation T790 M in non-small cell lung cancer patients with active exon 19Del and exon 21 L858R: a systematic review and meta-analysis.

BACKGROUND: Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations, subsequent drug resistance is almost inevitable. The specific mechanisms of EGFR-TKI drug resistance can be identified through repeat biopsy. METHODS: To better understand the clinical characteristics of TKI resistance in NSCLC patients, we retrospectively reviewed studies of acquired TKI drug resistance using repeat biopsy from the last decade. The relevant literature was retrieved from January 2005 to August 2015 in the databases Medline and Embase. The search terms were NSCLC or non-small cell lung cancer and T790 M. RESULTS: A total of 478 patients with NSCLC tested by repeated biopsy were confirmed to have acquired TKI resistance. Analysis indicated that 240 patients (50.21%) of the 478 patients with acquired TKI drug resistance had the T790 M mutation. The detection rate of T790 M in different repeat biopsy sites was also different, with the highest positive rate in the lymph nodes (60%) and the lowest detection rate in cerebrospinal fluid (less than 5%). In addition, patients with T790 M had longer overall survival compared to those without the mutation (P < 0.05). Of the 240 patients with T790 M mutations, 213 patients showed results consistent with the mutation analysis before TKI treatment, and the rate of patients with the L858R point mutation along with the T790 M mutation was lower than that of patients with the exon 19 deletion (36.42% to 58.30%). CONCLUSIONS: T790 M occurred more frequently in patients with the exon 19 deletion than in those with exon 21 L858R, which gave the survival benefit of the T790 M mutation and may explain why patients with the exon 19 deletion had an improved overall survival.

Thick-wall cavity predicts worse progression-free survival in lung adenocarcinoma treated with first-line EGFR-TKIs.

BACKGROUND: Cavity occurs in 5.7 to 14.9% of patients with lung adenocarcinoma (ADC). However, the impact of cavity on the therapeutic response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in ADC patients with EGFR mutations remains unclear. The aim of the present retrospective study was to elucidate the incidence and detailed characteristics of EGFR-mutant cavitary ADC and investigate the efficacy of EGFR-TKI treatment in this subgroup. METHODS: Two hundred seventy-six consecutive patients with advanced EGFR-mutant lung ADC treated with first-line EGFR-TKIs were enrolled. Cavitation and the thickness of cavity wall were assessed based on high-resolution computed tomography scans. Progression-free survival (PFS) was analyzed by the Kaplan-Meier plots and the log-rank test was used to calculate the significance between groups. RESULTS: Cavity occurred in 5.4% (15/276) of patients with EGFR-mutant lung ADC and was more prevalent among male patients (66.7% vs. 33.3%, P = 0.008). Of the 15 EGFR-mutant cavitary ADC, 9 patients had exon 19 deletion (19DEL) and 6 harbored L858R mutation, 9 patients had thick-wall cavity while 6 had thin-wall cavity. Cavity had an adverse impact on the PFS of EGFR-mutant ADC treated with first-line EGFR-TKIs (noncavity versus cavity, 11.0 versus 6.5 months, hazard ratio [HR]: 0.33, 95% confidence interval [CI], 0.15-0.73, P = 0.003). The impaired effect was only observed in patients with L858R mutation (11.0 vs. 4.2 months, HR: 0.05, 95%CI, 0.01-0.27, P = 0.0003) but not in those with 19DEL (10.4 versus 9.7 months, HR: 0.73, 95%CI, 0.30-1.75, P = 0.483). All six L858R-mutant cavitary ADC patients had thick-wall cavity while thick-wall cavity was only identified in one thirds (3/9) of patients with 19DEL. Further analyses showed that patients with thick-wall cavity had worse PFS (6.0 versus 11.0 months, P = 0.013). Multivariate analysis identified cavity as an independent predictive factor for PFS (HR: 0.49, 95% CI, 0.26-0.90, P = 0.022). CONCLUSION: Cavitary ADC was associated with a worse PFS of first-line EGFR-TKI therapy, mainly in those with L858R mutation. Thick-wall cavity formation may be the main cause that contribute to the worse PFS.

Comprehensive evaluation of NT5E/CD73 expression and its prognostic significance in distinct types of cancers.

BACKGROUND: CD73 is one of the critical component in the formation of immunosuppressive microenvironment in cancers. We aimed to provide an overview of the current status of CD73 expression and its relationship with clinicopathlogical features and prognosis in different cancers. METHODS: PubMed, Web of Science, EMBASE and Cochrane library were searched to identify the relevant studies. CD73 expression level in distinct cancers and its relationship with clinicopathlogical characteristics and prognosis were investigated using online database. Meta-analyses were conducted using RevMan v5.0 and STATA v12.0. RESULTS: Fourteen publications with 2951 cases were included. The incidence of high CD73 expression was 0.50 (95% CI: 0.36-0.63). Data from Oncomine validated that median CD73 expression level in tumor tissues was markedly higher than that in normal tissues in most kinds of cancers except cecum adenocarcinoma and ovarian cancer (P < 0.05). High CD73 expression was significantly correlated with shorter overall survival (OS) in various cancers (high risk [HR] = 1.48; P < 0.05). Subgroup analysis using online database demonstrated that high CD73 expression was significantly correlated with poor OS in breast (HR = 1.23; P < 0.05) and ovarian cancer (HR = 1.14; P < 0.05), but favorable OS in lung (HR = 0.80; P < 0.05) and gastric cancer (HR = 0.71; P < 0.05). High CD73 expression was dramatically associated with lymph node metastases (OR = 2.61; P = 0.05). CONCLUSION: High CD73 expression was significantly associated with lymph node metastases and a promising prognostic factor in different types of cancers.

Highly tough, anti-fatigue and rapidly self-recoverable hydrogels reinforced with core-shell inorganic-organic hybrid latex particles.

The introduction of SiO2 particles as crosslinking points into hydrogels has been recognized as a suitable way for toughening hydrogels, due to their versatile functionalization and large specific surface area. However, chemically linked SiO2 nanocomposite hydrogels often exhibited negligible fatigue resistance and poor self-recoverable properties due to the irreversible cleavage of covalent bonds. Here, we proposed a novel strategy to improve stretchability, fatigue resistance and self-recoverable properties of hydrogels by using SiO2-g-poly(butyl acrylate) core-shell inorganic-organic hybrid latex particles as hydrophobic crosslinking centers for hydrophobic association. The obtained hydrogel could distribute the surrounding applied stress by disentanglement of the hybrid latex particles from hydrophobic segments. Based on this strategy, the formulated hydrogels showed an excellent tensile strength of 1.48 MPa, superior stretchability of 2511% and remarkable toughness of 12.62 MJ m-3. Moreover, the hydrogels owned extraordinary anti-fatigue, rapid self-recovery and puncture resistance properties. Therefore, this strategy provided a novel pathway for developing advanced soft materials with potential applications in biomedical engineering, such as tendons, muscles, cartilages, etc.

Super-tough, ultra-stretchable and strongly compressive hydrogels with core-shell latex particles inducing efficient aggregation of hydrophobic chains.

Toughness, strechability and compressibility for hydrogels were ordinarily balanced for their use as mechanically responsive materials. For example, macromolecular microsphere composite hydrogels with chemical crosslinking exhibited excellent compression strength and strechability, but poor tensile stress. Here, a novel strategy for the preparation of a super-tough, ultra-stretchable and strongly compressive hydrogel was proposed by introducing core-shell latex particles (LPs) as crosslinking centers for inducing efficient aggregation of hydrophobic chains. The core-shell LPs always maintained a spherical shape due to the presence of a hard core even by an external force and the soft shell could interact with hydrophobic chains due to hydrophobic interactions. As a result, the hydrogels reinforced by core-shell LPs exhibited not only a high tensile strength of 1.8 MPa and dramatic elongation of over 20 times, but also an excellent compressive performance of 13.5 MPa at a strain of 90%. The Mullins effect was verified for the validity of core-shell LP-reinforced hydrogels by inducing aggregation of hydrophobic chains. The novel strategy strives to provide a better avenue for designing and developing a new generation of hydrophobic association tough hydrogels with excellent mechanical properties.

Epithelial phenotype as a predictive marker for response to EGFR-TKIs in non-small cell lung cancer patients with wild-type EGFR.

Epithelial-to-mesenchymal transition (EMT) has profound impacts on cancer progression and also on drug resistance, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Nowadays, there is still no predictive biomarker identified for the use of EGFR-TKIs in non-small cell lung cancer (NSCLC) patients with wild-type EGFR. To clarify the role of EMT phenotype as a predictive marker for EGFR-TKI, we performed a retrospective study in 202 stage IV or recurrent NSCLC patients receiving gefitinib or erlotinib therapy from June 2008 to September 2012 in our institute. Clinical data and EGFR mutational status were collected, while epithelial, epithelial to mesenchymal, not specified or mesenchymal phenotype were classified according to EMT markers such as E-cadherin, fibronectin, N-cadherin and vimentin by immunohistochemistry. Epithelial phenotype was more frequently found in patients with EGFR mutation (p = 0.044). Epithelial phenotype was associated with a significantly higher objective response rate (23.5 vs. 11.1 vs. 0.0 vs. 2.4%, p = 0.011), longer progression-free survival (4.4 vs. 1.9 vs. 1.7 vs. 1.0 months, p < 0.001) and longer overall survival (11.5 vs. 8.9 vs. 4.5 vs. 4.9 months, p < 0.001) compared to epithelial to mesenchymal, not specified and mesenchymal phenotype in the wild-type EGFR subgroup. In the subgroup with EGFR mutation, the trend remained but without a statistically significant difference. In conclusion, epithelial phenotype was more likely expressed in patients with EGFR mutation and was associated with a better outcome in advanced NSCLC patients with wild-type EGFR, which indicates that the EMT phenotype might be a potential marker to guide EGFR-TKI therapy in this population.