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Auxetic metamaterials expand transversely when stretched longitudinally or contract transversely when compressed, resulting in a negative Poisson’s ratio (NPR). Auxetic fabrics are 3D textile metamaterials possessing a unique geometry that can generate an auxetic response with respect to tension. In weft-knitted auxetic fabrics, the NPR property is achieved due to the inherent curling effect of the face and back stitches of the knit loops; they contract in an organized knitting pattern. The traditional method used to evaluate NPR is to measure the lateral fabric deformation during axial tensile testing on a mechanical testing machine, which is time-consuming and inaccurate in measuring uneven deformations. In this study, an efficient method was developed to evaluate the NPR of weft-knitted fabric that can also estimate deformation directionality. The elasticity and extension properties of the weft-knitted fabric can be analyzed immediately following removal from the knitting bed. Five fabrics, all with the same stitch densities (including four auxetic patterns and one single jersey pattern), were designed and produced to validate the proposed method. The use of our estimation method to evaluate the Poisson’s ratio of such fabrics showed higher values compared with the traditional method. In conclusion, the deformation directionality, elasticity, and extensionality were examined. It is anticipated that the proposed method could assist in the innovative development and deployment of auxetic knitted metamaterials.

High-grade neuroendocrine tumors (NETs) of the lung consist of small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). Both exhibit aggressive malignancy with poor prognosis. The transformation of lung adenocarcinoma (ADC) to SCLC or LCNEC also contributes to acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Despite initially being responsive to chemotherapy, high-grade NET patients inevitably develop drug resistance; thus, novel therapeutic targets are urgently needed for these patients. Our study reported that VGF (nerve growth factor inducible), a factor mainly expressed in neurons during neural development, is highly expressed in SCLC and LCNEC as well as in a subset of ADCs, whereas targeting VGF attenuates cancer cell growth and tumor formation. High VGF expression was associated with advanced stage SCLC and predicted poor prognosis in lung ADC. In addition, EGFR-TKI selection enriched VGF expression in TKI-resistant ADC under epigenetic control. The VGF locus possessed the HDAC1 binding site, and treatment of ADC cells with the HDAC1 inhibitor induced VGF expression. High VGF expression was associated with chemoresistance, and silencing VGF induced BMF and BCL2L11 expression and rendered lung cancer cells sensitive to chemotherapy drugs. These findings suggested the potential of VGF as a prognostic factor and therapeutic target in lung cancers with neuroendocrine feature.

Mutations in EGFR drive tumor growth but render tumor cells sensitive to treatment with EGFR tyrosine kinase inhibitors (TKI). Phenotypic alteration in epithelial-to-mesenchymal transition (EMT) has been linked to the TKI resistance in lung adenocarcinoma. However, the mechanism underlying this resistance remains unclear. Here we report that high expression of a neuroendocrine factor termed VGF induces the transcription factor TWIST1 to facilitate TKI resistance, EMT, and cancer dissemination in a subset of lung adenocarcinoma cells. VGF silencing resensitized EGFR-mutated lung adenocarcinoma cells to TKI. Conversely, overexpression of VGF in sensitive cells conferred resistance to TKIs and induced EMT, increasing migratory and invasive behaviors. Correlation analysis revealed a significant association of VGF expression with advanced tumor grade and poor survival in patients with lung adenocarcinoma. In a mouse xenograft model of lung adenocarcinoma, suppressing VGF expression was sufficient to attenuate tumor growth. Overall, our findings show how VGF can confer TKI resistance and trigger EMT, suggesting its potential utility as a biomarker and therapeutic target in lung adenocarcinoma. Cancer Res; 77(11); 3013–26. ©2017 AACR.

'Figure S1. Lack of T790M and amplification of MET in HCC827GR cells; Figure S2. VGF-expressing cells are resistant to rociletinib; Figure S3. VGF expression in neuroendocrine carcinoma and EGFR-TKI resistant cells; Figure S4. VGF is expressed in the independently selected EGFR-TKI resistant HCC827 pool; Figure S5. Correlation of VGF levels with EGFR-TKI resistance and EMT in EGFR-TKI selected single cell clones; Figure S6. Effect of VGF expression on cell survival; Figure S7. VGF is highly expressed in small cell lung cancer; Figure S8. VGF is highly expressed in large cell neuroendocrine carcinoma; Figure S9. Correlation of VGF, CEACAM6, SYP, and CHGB expression levels with IC50 values of gefitinib in EGFR-mutated lung cancer cell lines; Figure S10. EGFR-TKI resistance in H1975 cells expressing differential VGF levels; Figure S11. VGF-TWIST1 signaling encourages EGFR-TKI resistance; Figure S12. Effect of conditioned medium from VGF expressing cells on low serum-mediated growth; Figure S13. Effect of doxycycline alone on tumor cell growth in vitro and in vivo; Figure S14. Correlation of VGF with EMT markers in lung adenocarcinoma; Figure S15. Correlation of neuroendocrine markers or TWIST1 with survival in lung adenocarcinoma; Figure S16. Correlation of neuroendocrine markers or VGF-TWIST1 signature with survival in EGFR-mutated lung adenocarcinoma.'

'Table S1. Q-PCR primer and probe sequences for quantifying gene expression; Table S2. Q-PCR primer and probe sequences for quantifying gene amplification; Table S3. Antibodies for Western blot; Table S4. Antibodies for immunofluorescence; Table S5. Gene expression profiling data from the public domain used in this study.'

'Establishment of gefitinib-resistant cell lines; RNA extraction and quantitative real-time polymerase chain reaction (Q-PCR); Genomic DNA extraction and DNA sequencing; AlamarBlue® viability assay; Xenograft tumorigenicity assay; RNA In Situ Hybridization; Immunomagnetic reduction (IMR) assay.'

Two-dimensional (2D) perovskite have been widely researched for solar cells, light-emitting diodes, photodetectors because of their excellent environmental stability and optoelectronic properties in comparison to three-dimensional (3D) perovskite. In this study, we demonstrate the high response of 2D-(PEA)

Omicron variants of SARS-CoV-2 has been dominantly distributed worldwide since December 2021. Sequence analysis has revealed a 9 base pair (bp) nucleotide deletion located in N gene was found in Omicron strains but not in other prevalent variants. Based on this feature, we have developed a highly specific and sensitive real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay for differentiating Omicron lineages from other SARS-CoV-2. With this unique design of primers and probes, we consider this approach could be applied to identify particular genome feature for future SARS-CoV-2 variant characterization.

Purpose To investigate the clinical feature of tuberculosis and BCG adverse effects in children and to examine whether delayed BCG vaccination changes the incidence of BCG osteomyelitis. Methods We analyzed patients younger than 18 years with tuberculosis or BCG-associated adverse effects from 2008 to 2019. We compared their clinical features, laboratory tests and outcomes. Results Totally 137 patients were collected, with 27% of pulmonary tuberculosis (PTB), 31% of extrapulmonary tuberculosis (EPTB) and 42% of BCG-associated adverse effects. The median age was older in PTB than EPTB group (17.1 vs 15.4 years; p = 0.015). More patients in EPTB group had fever than PTB group (55% vs 25%; p = 0.008). Compared with exclusively EPTB, more patients in EPTB plus PTB group had fever (78% vs 38%; p = 0.009), and had more systemic symptoms (67% vs 25%; p = 0.007), lower absolute lymphocyte count (1230 vs 1850/μL; p = 0.033), higher CRP level (5.62 vs 2.21 mg/dL; p = 0.024) and longer hospital stay (20 vs 11 days; p = 0.031). In BCG osteomyelitis group, the median time interval from vaccination to diagnosis was 16.4 months (IQR 15.0–20.2). Age at vaccination, either at birth or 5-8 month-old, did not affect the proportion of BCG osteomyelitis among children with BCG-associated adverse effects. Conclusion Children with EPTB plus PTB had more fever, lower lymphocyte count and higher CRP. The median time interval from vaccination to diagnosis of BCG osteomyelitis was 16.4 months and the proportion of BCG osteomyelitis among children with BCG-associated adverse effects was not affected by delayed vaccination in this study.

Background/Purpose Despite the high prevalence of Mycoplasma pneumoniae infections, reports on severe life-threatening M. pneumoniae pneumonia (MPP) in children are limited. Methods We retrospectively enrolled pediatric patients with PCR-positive MPP requiring ICU admission in a children's hospital in Taipei, Taiwan from Jun 2010 to October 2019. Clinical manifestations and laboratory data of severe MPP were analyzed. Macrolide susceptibility was determined by genotyping, and its relationship with clinical manifestations was also analyzed. Results Approximately 5% (34/658) children hospitalized for MPP required ICU admission. Compared with non-ICU cases (n = 291), ICU cases (n = 34) were associated with more underlying conditions, more pleural effusion, longer fever duration, longer hospital stay, the requirement of second-line antibiotic treatment, and delayed effective and second-line antibiotic treatment. Macrolide resistance was similar in ICU and non-ICU groups (53% vs 53%; p = 0.986). In severe MPP, patients requiring endotracheal intubation were associated with more septic shock, empyema, ARDS, prolonged fever after effective antibiotic treatment, delayed second-line and effective antibiotic treatment. In 18 of the 22 patients with pleural fluid analysis, the pleural effusion was alkaline (pH > 7.7) and lymphocyte-predominant. Conclusion M. pneumoniae infection can cause severe life-threatening pneumonia in children. Delayed effective and second-line antibiotic treatments are associated with severe life-threatening MPP.

We present a display consisting of a 64-cell quantum dot (QD) light-emitting diodes (LEDs) array manufactured by spin coating and steel plate design evaporation technology. The QDLED pixels in the array can be driven independently. The surface of perovskite nanocrystal (NC) composite was modified by using pure natural material aloe-vera gel as the organic precursor to obtain high-quality narrow band photoluminescence emission all-inorganic CsPbBr3 perovskite NC composites. Here, an open-source Arduino microcontroller unit was used as the dynamic micro-control terminal, combined with a step-down module and four motor drive modules to make the display driver circuit. Finally, a 99% operating rate and a maximum brightness of 3366 cd $\text{m}^{-2}$ were achieved in the 8 $\times $ 8 perovskite QDLEDs array display. Furthermore, an electroluminescence dynamic pattern display based on a 64-cell QDLEDs array display has been successfully demonstrated. This study demonstrates the potential of perovskite devices for next-generation displays.

Perovskite solar cells (PSCs) have been made eligible for proficient power conversion efficiency (PCE) by optimizing the perovskite film’s morphology, formation, interfaces, and charge collection for increased effectiveness. This paper applied a new method for Cu2O/methylammonium lead iodide (MAPbI3)/SiO2 structure with heterojunction PSCs. This paper developed a novel synthesis engineering method for thin Cu2O hole-transporting material layer (HTML) and ultrathin SiO2 electron-transporting material layer (ETML). Cu2O HTML and SiO2 ETML could improve the PCE and carrier charge for recombination and recollection. The architecture includes a reduced film thickness by hetero-contact synthesis engineering, which resulted in an impactful enhancement of open-circuit voltage (Voc). The stable Voc effect was induced by constructing the interfilm of Cu2O and SiO2 between the main CH3NH3PbI3 layers, which transported electrons/electron holes, resulting in an excellent PCE of 18.4%. The fabrication showed that inorganic materials can be applied for the potential interfacial engineering of perovskite-based solar cells.

For future space transportation and planetary exploration mission power applications, NASA Glenn Research Center (GRC) is currently developing a small-scale nuclear fission system (i.e. Kilopower system), which has an operable range of 1 to 10 kWe and a design life of 8 to 15 years. The thermal management system of Kilopower system involves two types of heat pipes: high temperature alkali metal heat pipes that are used to transport thermal energy from the nuclear reactor to the Stirling convertors hot end and titanium water heat pipes that are used to remove the waste heat from the convertors cold end and transport it to the radiators for ultimate rejection. This paper presents the development of the titanium water heat pipes, which are featured with a special wick structure design: it has bi-porous screened evaporator and screen-groove hybrid wick in the adiabatic and condenser sections. This will allow the heat pipe to (1) operate in space with zero gravity (2) operate on planetary surface with gravity-aided orientation (3) be tested on ground with slight adverse gravity orientation and (4) to startup smoothly after being frozen. Under a research and development program, several freeze/thaw tolerant heat pipes were designed, fabricated and experimentally validated. Later, various heat pipe radiators were developed and tested in a thermal vacuum chamber (TVC). Test results successfully demonstrated that the titanium heat pipes with radiator attached are able to transfer the required power at the working temperature of 400 K under space-like testing conditions with a thermal resistance of 0.019 °C/W while the total heat pipe radiator weight is less than 0.73 kg.

Naturally evolved immune-escape PreS2 mutant is an oncogenic caveat of liver cirrhosis and hepatocellular carcinoma (HCC) during chronic hepatitis B virus (HBV) infection. Notably, PreS2 mutants is prevalent in above 50% of patients with HCC. Intrahepatic expression of PreS2 mutant large surface antigen (PreS2-LHBS) induces endoplasmic reticulum stress, mitochondria dysfunction, cytokinesis failure and subsequent chromosome hyperploidy. In this study, we ask if long-term inhibition of PreS2-LHBS may act to reverse HBV-mediated hepatocarcinogenesis. We set up a stability reporter platform and identified ABT199 as an inhibitor of PreS2-LHBS from a library of 1068 FDA-approved drugs. Treatment of ABT199 induced PreS2-LHBS degradation without affecting the general cell viability, as shown in hepatoma and immortalized hepatocyte cell lines. We found that ABT199 induced the recruitment of PreS2-LHBS to ring-shaped structures in close proximity to lysosomal marker Lamp1 and multivesicular body marker Rab7. Simultaneously, inhibitions of lysosomal degradation or microautophagy restored the expression of PreS2-LHBS. Specifically, a 24-hr treatment of ABT199 reduced DNA damages and cytokinesis failure induced by PreS2-LHBS. Persistent treatment of ABT199 for 3 weeks reversed chromosome hyperploidy in PreS2-LHBS cells and suppressed anchorage-independent growth of HBV-positive hepatoma cell line. Together, we showed that ABT199 provoked selective degradation of PreS2-LHBS through the induction of microautophagy, and a long-term treatment of ABT199 reversed oncogenic mechanisms induced by HBV. Our results indicate that long-term degradation of PreS2-LHBS may serve as a novel therapeutic strategy to constrain HBV-mediated hepatocarcinogenesis.Graphical abstractAuthor summaryHBV PreS2 mutant large surface antigen (PreS2-LHBS) is an oncoprotein that induces liver cirrhosis and liver cancer. This study identified ABT199 as a potential inhibitor of PreS2-LHBS. We found that ABT199 could trigger the degradation of PreS2-LHBS through the induction of microautophagy. Moreover, a long-term treatment of ABT199 significantly reversed LHBS-induced oncogenic events including DNA damage, mitotic failure, chromosome hyperploidy, and anchorage-independent growth. This study not only identifies a specific inhibitor of PreS2-LHBS but also highlights a plausible strategy to constrain HBV-mediated hepatocarcinogenesis through targeting the degradation of PreS2-LHBS.

Naturally evolved immune-escape PreS2 mutant is an oncogenic caveat of liver cirrhosis and hepatocellular carcinoma (HCC) during chronic hepatitis B virus (HBV) infection. PreS2 mutant is prevalent in above 50% of patients with HCC. In addition, intrahepatic expression of PreS2 mutant large surface antigen (PreS2-LHBS) induces endoplasmic reticulum stress, mitochondria dysfunction, cytokinesis failure, and subsequent chromosome hyperploidy. As PreS2-LHBS has no enzymatic activity, the development of PreS2-specific inhibitors can be challenging. In this study, we aim to identify inhibitors of PreS2-LHBS via the induction of protein-specific degradation. We set up a large-scale protein stability reporter platform and applied an FDA-approved drug library for the screening. We identified ABT199 as a negative modulator of PreS2-LHBS, which induced the degradation of PreS2-LHBS without affecting the general cell viability in both hepatoma and immortalized hepatocytes. Next, by affinity purification screening, we found that PreS2-LHBS interacted with HSC70, a microautophagy mediating chaperone. Simultaneously, inhibitions of lysosomal degradation or microautophagy restored the expression of PreS2-LHBS, suggesting microautophagy is involved in ABT199-induced PreS2-LHBS degradation. Notably, a 24-hr treatment of ABT199 was sufficient for the reduction of DNA damage and cytokinesis failure in PreS2-LHBS expressing hepatocytes. In addition, a persistent treatment of ABT199 for 3 weeks reversed chromosome hyperploidy in PreS2-LHBS cells and suppressed anchorage-independent growth of HBV-positive hepatoma cells. Together, this study identified ABT-199 as a negative modulator of PreS2-LHBS via mediating microautophagy. Our results indicate that long-term inhibition of PreS2-LHBS may serve as a novel strategy for the therapeutic prevention of HBV-mediated HCC.

This work describes the effect of a rubidium chloride (RbCl) interlayer in CsPbBr3 perovskite light-emitting diode (LED) structures. RbCl crystallites exhibited polyhedral structures and lattice parameters similar to those of CsPbBr3 perovskite crystallites. The lattice mismatch between the RbCl interlayer and CsPbBr3 active layer was only approximately 2%. The devices exhibited the best quality and performance when RbCl was used as the nucleation and carrier confinement layer. The crystallite sizes of CsPbBr3 with 0.2-, 0.5-, and 1-nm-thick RbCl bottom layers were 55.1, 65.4, and 55.1 nm, respectively. The full width at half maximum (FWHM) of the photoluminescence (PL) emission peak for CsPbBr3 with the RbCl bottom layer was 0.096 eV.

Bottom ash (BA) from incineration has been reused as a construction material for years. However, thermal treatments, which incur extra cost and higher energy demand, are essential to reduce/stabilize the polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in BA, which can be released from BA during the next startup and cause peak emissions. In this study, the bottom ash from a laboratory waste incinerator (LWI) was collected and quenched at various temperatures during three shutdown operations to determine the results of the gradual cooling process. The PCDD/F content in the BA was quantified using gas chromatography-mass spectrometry. The PCDD/Fs in BA was significantly lower (0.0239 ng WHO-TEQ g−1) after being quenched at >400 °C, which was only 1/300 of that in the sample gradually cooled to 0.97. In other words, careful operation of the cooling process is an important PCDD/F inhibition strategy and effectively reduces the subsequent startup emissions. Interestingly, the extremely low PCDD/F levels in the BA after quenching were found to further save the cost of thermal treatment, reduce electricity use by 500 MWh, and lower fuel consumption by 27 kL of diesel, as well as reducing annual CO2e emissions by 351 tons in an LWI. This finding could be further applied to simultaneously control PCDD/F emissions, save post-treatment costs, and reduce the secondary pollutants in other incinerators.

Advanced Cooling Technologies, Inc. (ACT) is developing a heat pipe-based thermal delivery system to efficiently manage the waste heat of an electric aircraft. The heat pipe system will be integrated with thermoacoustic heat pump tubes developed by NASA Glenn Research Center (GRC). This paper will discuss the design of a full-scale heat pipe layout for a MW-class commercial electric aircraft based on the NASA inputs, including operating temperatures, power and relative distances/elevations of heat sources, heat pump tubes and end users. Experimental results of a prototype long and curved thermosyphon designed to transport heat from the turbofan to the wing will be presented. Finally, a two-phase heat transport system with solid-state thermal switching/control capabilities based on variable conductance heat pipe technology that will be used to control the heat transfer rate to various end users will be introduced and experimentally demonstrated.

Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking, we showed that both Etravirine and Dolutegravir are preferentially bound to primary ACE2-interacting residues on the RBD domain, implying that these two drug blocks may prohibit the viral attachment of SARS-CoV-2. We compared the neutralizing activities of these entry inhibitors against different pseudoviruses carrying spike proteins from alpha, beta, gamma, and delta variants. Both Etravirine and Dolutegravir showed similar neutralizing activities against different variants, with EC50 values between 4.5 to 5.8 nM for Etravirine and 10.2 to 22.9 nM for Dolutegravir. These data implied that Etravirine and Dolutegravir may serve as general spike inhibitors against dominant viral variants of SARS-CoV-2.

Probes to penetrate the thick ice shells of our solar system’s Ocean Worlds have been studied for nearly 20 years, since scientific evidence strongly suggested a subsurface ocean on the Jupiter moon called Europa. There is keen scientific interest in exploring four significant themes on such proposed missions: 1) Geodynamics, 2) Geochemistry, 3) Habitability, and 4) Life Detection. The ice shells of Ocean Worlds are predicted to be up to 40 km thick; they exhibit extreme thermal environments, with ice temperatures from 100 K to 270 K, and extreme pressure environments from vacuum to 53 MPa. Jet Propulsion Laboratory has conducted a broad-look investigation of proposed mission concepts to Europa to identify the significant technology and operational challenges of Europa icepenetration. The thermal-mechanical system (TMS) of an ice penetration probe (IPP) mission concept designed to access the ocean of an icy moon using radioisotope thermoelectric generators for heat and power faces technological hurdles exacerbated by severe thermal and volume constraints. This study identified thermal management and control (TMC) challenges that are strongly linked to: ice penetration start-up, mobility and navigation in the ice, communications while in the ice sheet, and detecting and avoiding in-ice hazards. The major objectives of the TMC system are: 1) Absorb internal thermal energy from the IPP radioisotope power source, 2) Maintain liquid water conditions around the IPP at all times, 3) Manage and control thermal flows from probe nose to tail, and 4) Provide pressure containment for all internal probe components. This work discusses the baseline TMC system architecture and design developed to accomplish these objectives, and survive and transit the extreme ice thicknesses in pursuit of Icy/Ocean Worlds science goals. The proposed TMC system consisting of an internal pumped two-phase fluid loop “thermal bus” for thermal energy capture, variable conductance heat pipe system for passively adaptive thermal energy transport around the probe, and water jetting system for ice cutting is described and discussed. Critical testing performed to date is described.

This work presents a method for obtaining a color-converted red light source through a combination of a blue GaN light-emitting diode and a red fluorescent color conversion film of a perovskite CsPbI3/TOPO composite. High-quality CsPbI3 quantum dots (QDs) were prepared using the hot-injection method. The colloidal QD solutions were mixed with different ratios of trioctylphosphine oxide (TOPO) to form nanowires. The color conversion films prepared by the mixed ultraviolet resin and colloidal solutions were coated on blue LEDs. The optical and electrical properties of the devices were measured and analyzed at an injection current of 50 mA; it was observed that the strongest red light intensity was 93.1 cd/m2 and the external quantum efficiency was 5.7% at a wavelength of approximately 708 nm when CsPbI3/TOPO was 1:0.35.