Volume-Metallization 3D-Printed Polymer Composites.

3D printing polymer or metal can achieve complicated structures while lacking multifunctional performance. Combined printing of polymer and metal is desirable and challenging due to their insurmountable mismatch in melting-point temperatures. Here, a novel volume-metallization 3D-printed polymer composite (VMPC) with bicontinuous phases for enabling coupled structure and function, which are prepared by infilling low-melting-point metal (LM) to controllable porous configuration is reported. Based on vacuum-assisted low-pressure conditions, LM is guided by atmospheric pressure action and overcomes surface tension to spread along the printed polymer pore channel, enabling the complete filling saturation of porous structures for enhanced tensile strength (up to 35.41 MPa), thermal (up to 25.29 Wm-1K-1) and electrical (>106 S m-1) conductivities. The designed 3D-printed microstructure-oriented can achieve synergistic anisotropy in mechanics (1.67), thermal (27.2), and electrical (>1012) conductivities. VMPC multifunction is demonstrated, including customized 3D electronics with elevated strength, electromagnetic wave-guided transport and signal amplification, heat dissipation device for chip temperature control, and storage components for thermoelectric generator energy conversion with light-heat-electricity.

Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer Via Activation of the Fas Pathway.

BACKGROUND/AIM: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity. MATERIALS AND METHODS: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis. RESULTS: Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus. CONCLUSION: Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.

ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions.

Mutant p53 (mutp53) commonly loses its DNA binding affinity to p53 response elements (p53REs) and fails to induce apoptosis fully. However, the p53 mutation does not predict chemoresistance in all subtypes of breast cancers, and the critical determinants remain to be identified. In this study, mutp53 was found to mediate chemotherapy-induced long intergenic noncoding RNA-p21 (lincRNA-p21) expression by targeting the G-quadruplex structure rather than the p53RE on its promoter to promote chemosensitivity. However, estrogen receptor alpha (ERα) suppressed mutp53-mediated lincRNA-p21 expression by hijacking mutp53 to upregulate damaged DNA binding protein 2 (DDB2) transcription for subsequent DNA repair and chemoresistance. Levels of lincRNA-p21 positively correlated with the clinical responses of breast cancer patients to neoadjuvant chemotherapy and had an inverse correlation with the ER status and DDB2 level. In contrast, the carboplatin-induced DDB2 expression was higher in ER-positive breast tumor tissues. These results demonstrated that ER status determines the oncogenic function of mutp53 in chemoresistance by switching its target gene preference from lincRNA-p21 to DDB2 and suggest that induction of lincRNA-p21 and targeting DDB2 would be effective strategies to increase the chemosensitivity of mutp53 breast cancer patients.

Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection.

Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.

Cigarette smoke-induced LKB1/AMPK pathway deficiency reduces EGFR TKI sensitivity in NSCLC.

Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFRWT) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFRWT and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFRWT.

Development of policy performance indicators to assess the implementation of protection from exposure to secondhand smoke in China.

OBJECTIVE: To develop an approach for rapid assessment of tobacco control interventions in China. We examined the correlation between components of the Strength of Tobacco Control (SOTC) index and a proposed rapid evaluation indicator, the Policy Performance Indicator (PPI), which is based on protection of non-smokers from secondhand smoke (SHS). The PPI was used to assess the implementation of policies related to SHS at the provincial/municipal level in China. METHODS: Stratified random sampling was used to select five types of organisational and household respondents in two municipalities and five provinces in China (Shanghai and Tianjin, Heilongjiang, Henan, Guangdong, Zhejiang and Jiangxi, respectively). Data collection methods included key informant interviews, observation and intercept surveys (organisations), and a modified Global Adult Tobacco Survey (GATS) questionnaire (households). SOTC scores (SHS policy, capacity and efforts), PPI (no smoking in designated smoke-free places) and mid-term to long-term impact (knowledge, attitude and reduced exposure to SHS) were measured, and correlations among them were calculated. RESULTS: The PPI varied across the seven locations. Shanghai led in the component indicators (at 56.5% for indoor workplaces and 49.1% for indoor public places, respectively), followed by Guangdong, Tianjin and Zhejiang (at 30-35% for these two indicators), and finally, Henan and Jiangxi (at 20-25%). Smoke-free policies were more effectively implemented at indoor workplaces than indoor public places. The PPI correlated well with certain components of the SOTC but not with the long-term indicators. CONCLUSIONS: The PPI is useful for evaluating implementation of smoke-free policies. As tobacco control programmes are implemented, the PPI offers an indicator to track success and change strategies, without collecting data for a full SOTC index.