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Cancer progression including proliferation, metastasis, and chemoresistance has become a serious hindrance to cancer therapy. This phenomenon mainly derives from the innate insensitive or acquired resistance of cancer cells to apoptosis. Ferroptosis is a newly discovered mechanism of programmed cell death characterized by peroxidation of the lipid membrane induced by reactive oxygen species. Ferroptosis has been confirmed to eliminate cancer cells in an apoptosis-independent manner, however, the specific regulatory mechanism of ferroptosis is still unknown. The use of ferroptosis for overcoming cancer progression is limited. Noncoding RNAs have been found to play an important roles in cancer. They regulate gene expression to affect biological processes of cancer cells such as proliferation, cell cycle, and cell death. Thus far, the functions of ncRNAs in ferroptosis of cancer cells have been examined, and the specific mechanisms by which noncoding RNAs regulate ferroptosis have been partially discovered. However, there is no summary of ferroptosis associated noncoding RNAs and their functions in different cancer types. In this review, we discuss the roles of ferroptosis-associated noncoding RNAs in detail. Moreover, future work regarding the interaction between noncoding RNAs and ferroptosis is proposed, the possible obstacles are predicted and associated solutions are put forward. This review will deepen our understanding of the relationship between noncoding RNAs and ferroptosis, and provide new insights in targeting noncoding RNAs in ferroptosis associated therapeutic strategies.

Self-reported tobacco pack-year history plays a large role in decisions about low-dose CT screening for lung cancer, yet is challenging to measure accurately.To what extent does random measurement error in pack-year information impact screening decisions and screening effectiveness?Retrospective cohort study of 10,449 patients with pack-year history documented at least twice between October 2013 and July 2017 across 8 academic Veterans Affairs sites. Outcome measures included (1) observed reliability of pack-year information based on all repeat measures for the study population and (2) each person's statistically "true" pack-year information based on best linear unbiased predictor from a multilevel linear random effects model. To examine how unreliability leads to misclassification of screening eligibility and inaccuracy in estimating lung cancer risk, we simulated pack-year observations for each person, first comparing simulated pack-year and lung cancer risk values with true values, then comparing outcomes when basing screening decisions on unreliable pack-year information vs true information.Reliability of assessing pack-year information in routine practice varied across sites. Thus, we examined the clinical impact of two different levels of reliability, based on the range of intraclass correlation coefficients observed. Using a ≥ 30-pack-year threshold led to a high rate of eligibility misclassifications (48.1% misclassified with higher reliability pack-year information and 60.7% misclassified with lower reliability information). However, using a lung cancer risk threshold leads to fewer misclassifications (47.3%-49.7% misclassified when using lower reliability pack-year information) and maintains screening effectiveness better when using unreliable pack-year information.Random error in real-world pack-year assessments leads to a substantial rate of misclassifying who should be offered CT screening if a ≥ 30-pack-year criterion is used. However, using a lung cancer risk threshold mitigates the impact of unreliable pack-year information. Decision-makers concerned about the impact of unreliable pack-year information should consider using risk-based approaches to CT screening.

Purpose The purpose of this study was to investigate the molecular mechanism of LncRNA LOXL1-AS1 in non-small cell lung cancer (NSCLC). Methods Lung cancer cell lines (H1299, A549, H520 and H596) and human normal lung epithelial cell line (BEAS-2B) were used in this study. Gene expression was measured by qRT-PCR (quantitative real-time PCR). The bioinformatics databases (miRDB and TargetScan7) were used to predict target genes. Luciferase assay and pull-down assay were processed for verifying the binding sites. CCK8 assay was used for detecting proliferation, and transwell assay was undertaken for migration and invasion. Results LncRNA LOXL1-AS1 was higher expressed in lung cancer tissues and cells. Moreover, LOXL1-AS1 expression was upregulated in tumor tissues with advanced stages and metastasis. After knocking down LOXL1-AS1, proliferation, invasion and migration of H1299 and A549 cells were inhibited. Interestingly, miR-3128 was negatively regulated by LncRNA LOXL1-AS1, which inhibited the expression of RHOXF2. Rescue assay also confirmed that miR-3128 inhibitor and oeRHOXF2 could rescue the effect of down-regulated LOXL1-AS1 on proliferation, invasion and migration progression. Conclusion LOXL1-AS1 promotes the progression of NSCLC by regulating miR-3128/RHOXF2 axis, which might be a new potential target for the diagnosis and treatment of NSCLC.

Boiler drum water level control system is hard to develop practical mathematical model and has nonlinear, stable and delay characteristics. The traditional boiler drum water level control often uses three impulse PID control method. The existing problem of ordinary PID control strategy is: once good parameter setting, it is hard to adapt to the change of the operation of the system dynamic greatly. In order to solve the problems of the above, the research object of the subject is a certain 120 t/h boiler steam capacity, the boiler drum water level control system is designed, and the control strategies are studied. In order to obtain better contrast, the ordinary PID controller and Fuzzy controller are designed, and the control strategies of the simulation are analyzed.

With the increase of electromagnetic radiation pollution, there is an urgent need to develop lightweight, ultra-thin, and high electromagnetic shielding composite film to eliminate unwanted electromagnetic interference. Herein, based on the layer-by-layer assembly strategy, a simple solution dip coating method was used to achieve the combination of two-dimensional transition metal (MXene) and nanofiber film, thereby constructing a conductive composite film with a unique undulating structure. The silicon-containing hydrophobic layer imparted excellent hydrophobic properties to the composite film while maintained the stability of the sandwich structure. The contact angle (CA) of the composite film with ultra-thin thickness (29um) was 125.49° and the conductivity was as high as 71.91 S/cm. The hydrophobic treatment would not damage the flexibility and mechanical properties of the composite film. In particular, the average shielding effectiveness (SE) and SSE/t could as high as 28.82 dB and 12422.41 dB cm2g−1, due to the layered structure formed by the connection of countless MXene nanosheets is beneficial to promote multiple absorption and reflection. This layer-by-layer assembly strategy provides a facile route in fabricating light-weight, flexible and ultrathin composite film for high-performance electromagnetic shielding, which is of great significance for broadening the practical application of MXene-based conductive materials.

Water was the source of life, in order to solve the serious water pollution problem facing the world, researchers have proposed many solutions. Among them, photoelectric catalytic technology based on semiconductor materials was an ideal and sustainable solution. Herein, by combining successive ionic layer adsorption and reaction (SILAR) with sol-gel electrospinning two strategies, a novel S-scheme heterojunction based on flexible and hierarchical BiOI/TiO2 nanofibrous membranes (BiOI/TiO2 NFM) was fabricated. The degradation rates of tetracycline (TC) and Rhodamine B (RHB) were 98.7% and 95.6%, respectively, under visible light irradiation. The main reason, except for the benefits offered by the hierarchical nanofiber structure, such as the large surface area, tightly connected interfaces and more exposed active sites, other advantages derived from photogenerated carrier transfer and superior redox ability were also momentous. To reveal the formed S-scheme heterojunction, a variety of test methods were used to characterize and test. These studies showed a significant increase in charge separation efficiency in the BiOI/TiO2 NFM, and the charge transport of S-scheme heterojunction was demonstrated. This study may offer new design ideas for the design and construction of novel structures of S-scheme heterojunctions.

A multi-stage electrochemical method was developed to synthesize palladium (Pd) nanoparticles supported on hydroxyapatite (HA) coatings. In the first stage, a dense coating of HA nanocrystals was synthesized from an aqueous electrolyte solution onto a titanium cathode surface through a galvanostatic process. The HA-coated titanium electrode was then used as the cathode for the electrochemical reduction of Pd2+ from aqueous solution. A synthesis approach using two sequential electrochemical reduction reactions was found to be more effective in producing uniform coatings of Pd nanoparticles than a single stage reduction. In the first step, a higher voltage was applied to the cathode for a short time to promote the nucleation of Pd nanoparticles. A lower voltage was then applied for a longer time in the second stage to promote the growth of the Pd nanoparticles. The size and size distribution of the Pd nanoparticles were controlled by adjusting the duration of the first and second stages of electrochemical reduction. The resulting HA supported Pd nanoparticles demonstrated significantly higher catalytic activity than commercial Pd nanoparticles in the degradation of methyl orange by NaBH4. The high surface area and the complex oxidation states of the HA-supported Pd nanoparticles are believed to account for the enhanced catalytic activity.

Background: Effects of pH (6-8), protein concentration (60-110, g kg-1 ), heating temperature (70-95 °C) and time (5-30 min) on physiochemical and rheological properties of thermal-induced polymerized whey protein isolate (PWP) were systematically investigated. Degree of denaturation, particle size, zeta potential, free sulfhydryl group content, surface hydrophobicity and apparent viscosity were determined.; Results: Heating whey protein above 75 °C at pH 7 or 8 resulted in denaturation of 80-90% whey protein. pH variation had a remarkable influence on particle size of samples (P < 0.05), whereas heating temperature and time did not generate significant changes. Zeta potential of PWP samples fell in the range of -30 to -40 mV. Free sulfhydryl group content of PWP samples decreased with increasing level regarding each factor. Surface hydrophobicity analysis showed that samples at higher pH or concentration became less hydrophobic, and increasing heating temperature or time resulted in higher hydrophobicity index. Time sweep test revealed that increasing protein concentration, heating temperature or time led to higher apparent viscosity. Flow behavior of PWP samples approached Newtonian character as protein concentration, heating temperature or time decreased.; Conclusion: Systematic data may provide helpful information in designing a heating process for dairy products and application of PWP in the food industry. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

Content cache for Vehicle Edge Computing (VEC) Network is a promising service to reduce transmission delay and cost. Existing content cache system requires Road Side Units (RSUs) to participate in the content transmission process, however, RSUs are usually distributed along the road without strong security protection, which is vulnerable to being compromised by attackers. In this way, the cached content is vulnerable to tamper and the widespread dissemination of malicious content will bring a devastating blow to the trust mechanism of the caching system. In this paper, we propose a Blockchain-empowered content cache system, where the content index (containing the provider’s address, the hash value of the content) is adopted to guarantee the validity of the content. The content index is deposited in the Blockchain system, the immutability and distributed architecture of Blockchain can effectively prevent the content index from being tampered. However, such tamper-resistance property comes at the cost of a long confirmation caused by the consensus process. A time-oriented Proof of Work (PoW) consensus algorithm is proposed to improve the Blockchain efficiency. And a local indexing set-based search mechanism is established to reduce the long search delay caused by the chain-based structure. Moreover, the simulation results also demonstrate that the Blockchain-empowered cache system can improve the hit ratio of servers by providing customized request information.

Purpose To investigate molecular characteristics and antimicrobial susceptibility profiles of clinical isolates of Elizabethkingia in Shanghai, China. Methods Elizabethkingia isolates were collected in a university-affiliated hospital in 2012–2015 and 2017–2018. They were re-identified to species level by 16S rRNA gene and species-specific gene sequencing. Antimicrobial susceptibility testing, screening for metallo-beta-lactamase production, identification of antimicrobial resistance genes and pulsed-field gel electrophoresis (PFGE) were performed. Results Among 52 Elizabethkingia isolates, E. anophelis was the most prevalent species (67.3%), followed by E. meningoseptica (26.9%). High carriage rates of blaCME, blaBlaB and blaGOB genes were consistent with the poor in vitro activity of most β-lactams including carbapenems. Nevertheless, β-lactamase inhibitors increased susceptibility rates significantly for cefoperazone and piperacillin. Susceptibility rates for minocycline, tigecycline, rifampin and levofloxacin were 100%, 78.8%, 76.9% and 71.2%, respectively. Ser83Ile or Ser83Arg substitution in the DNA gyrase A unit was associated with resistance to fluoroquinolones. MIC50/MIC90 values of vancomycin and linezolid were 16/16 mg/L and 16/32 mg/L, respectively. Molecular typing showed twenty-one different types of PFGE and more than one indistinguishable isolates were observed in each of the eight subtypes. Conclusion Tetracyclines, tigecycline, β-lactam/β-lactamase inhibitor combinations, rifampin and fluoroquinolones demonstrated high rates of in vitro activity against clinical isolates of Elizabethkingia. Both genetic diversity and clonality were observed from this health-care facility. Our report provides potential alternative treatment options for Elizabethkingia infections.

The development of plug-in electric vehicles (PEVs) brings lucrative opportunities for charging station operators (CSOs). To attract more CSOs to the PEV market, provision of reasonable pricing policy is of great importance. However, dynamic environments and uncertain behavior of competitors make the pricing problem of CSOs challenging. In this paper, we focus on the dynamic pricing policy for maximizing the long-term profits of CSOs. Firstly, we propose a hierarchical framework to describe the economic association of PEV market, which is composed of smart grid, CSOs and charging stations (CSs) serving PEVs from top to bottom. Next, we leverage the Markov game to model the layer of CSOs as a competitive market. Finally, we design a dynamic pricing policy algorithm (DPPA) based on multi-agent reinforcement learning to achieve higher long-term profits of CSOs. Based on the real data of PEVs in Beijing, the experiment results show that DPPA has a significant improvement in long-term profit of CSOs, and the improvement gains increase over time. Moreover, DPPA can reduce the profit loss of CSOs effectively while involving more competitors.

In this paper, wheat straw, corn straw and sorghum straw were used as raw materials. KOH and NaOH were used as catalysts to prepare straw pyrolytic carbon. The effects of pyrolysis temperature, KOH, NaOH and NaOH–KOH on the properties and combustion characteristics of straw pyrolytic carbon were studied. Compared with straw pyrolytic carbon, the fixed carbon content of base-catalyzed straw pyrolytic carbon decreased notably and the ash content increased significantly. KOH had the basically same effect on straw pyrolytic carbon, but for corn straw pyrolytic carbon (CSPC) it was greater. KOH with low additive amount could improve the SN of straw pyrolytic carbon to some extent. NaOH had the basically same effect on straw pyrolytic carbon but was relatively stronger on wheat straw pyrolytic carbon (WSPC). NaOH with a concentration of 1.0–1.5 (mass ratio) showed the largest improvement of SN in straw pyrolytic carbon. When adding mixed alkalis, the combustible components of WSPCNa–KOH1-1, CSPCNa–KOH1-1, SSPCNa–KOH1-1 (sorghum straw pyrolytic carbon) were the highest and the corresponding SN was at its minimum.

Background and objective So far there’s no tumor maker applied in diagnosis and treatment of thymic epithelial tumors. This study is to assess the correlation between serum cytokine 19 fragment (Cyfra 21-1) and clinicopathological features and prognosis of thymic epithelial tumors (TETs). Methods The clinical data of 159 patients with TETs in Shanghai Chest Hospital was retrospectively analysed. Patients were divided into groups according to different tumor stages and histotypes. Serum Cyfra 21-1 was thus compared. In addition, the possible relationship between perioperative serum Cyfra 21-1 level and the recurrent status was carrid out. Results Preoperative Cyfra 21-1 serum concentrations in patiants with advanced stage (T4) and thymic carcinomas were significantly higher than that in others (P

Surgery is the most important therapy for thymic malignancies. The last decade has seen increasing adoption of minimally invasive thymectomy (MIT) for thymic tumors. MIT for early stage diseases has been shown to yield similar oncological results while being helpful in minimizing surgical trauma, improving postoperative recovery, and reducing incisional pain. Similar surgical and oncological principles should be observed in both minimally invasive and open procedures so as to ensure radical resection and accurate staging of the tumor.

Podophyllotoxin (PPT) is a chemotherapeutic agent which has shown significant activity against P-glycoprotein (P-gp) mediated multi drug resistant cancer cells. However, because of the poor aqueous solubility and high toxicity, PPT cannot be used in clinical cancer therapy. In order to enhance the efficiency and reduce side effect of PPT, a polypeptide based PPT conjugate PLG-g-mPEG-PPT was developed and used for the treatment of multi drug resistant breast cancer. The PLG-g-mPEG-PPT was prepared by conjugating PPT to poly( l -glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-mPEG) via ester bonds. The PPT conjugates self-assembled into nanoparticles with average sizes about 100 nm in aqueous solution. Western blotting assay showed that the PLG-g-mPEG-PPT could effectively inhibit the expression of P-gp in the multiple drug resistant MCF-7/ADR cells. In vitro cytotoxicity assay indicated that the resistance index (RI) values of PLG-g-mPEG-PPT on different drug-resistant cancer cell lines exhibited 57–270 folds reduction than of traditional microtubule inhibitor chemotherapeutic drug PTX or DTX. Hemolysis assay demonstrated that the conjugation greatly decreased the hemolytic activity of free PPT. Maximum tolerated dose (MTD) of PLG-g-mPEG-PPT increased greatly (13.3 folds) as compared to that of free PPT. In vivo study showed that the PLG-g-mPEG-PPT conjugate remarkably enhanced the antitumor efficacy against MCF-7/ADR xenograft tumors with a tumor suppression rate (TSR) of 82.5%, displayed significantly improved anticancer efficacy as compared to free PPT (TSR = 37.1%) with minimal toxicity when both of the two formulations were used in MTD. Statement of Significance The development of multiple drug resistance (MDR) of cancer cells is the main cause of chemotherapy failure. The over-expression of P-glycoprotein (P-gp) has been recognized to be the most important cause of MDR in cancer. Podophyllotoxin (PPT) is a chemotherapeutic agent which has shown strong activity against P-gp mediated multidrug resistant cancer cells by simultaneously inhibiting the over-expression of P-gp and the growth of cancer cells. However, PPT can not be used in clinical cancer treatment due to its poor aqueous solubility and high toxicity. Herein, we developed a polypeptide based PPT conjugate PLG-g-mPEG-PPT by conjugating PPT to poly( l -glutamic acid)-g-methoxy poly(ethylene glycol). The PLG-g-mPEG-PPT shows significantly decreased hemolytic activity, greatly improved maximum tolerated dose and remarkably enhanced antitumor efficacy against MCF-7/ADR xenograft tumors as compared to free PPT.

The traditional chemotherapy using single agent may suffer from serious drawbacks, particularly dose-limiting toxicity and relatively low antitumor efficacy, which can lead to failure of chemotherapy. Co-delivery of two or more therapeutic drugs in nanotechnology is a potential strategy to generate synergistic anticancer effects and reduce individual drug-related toxicity, but explosive release of each drug from multi-drug loaded nanoparticles has been a distinct obstacle. In this study, a novel amphiphilic and biodegradable triblock copolymer, named MPEG-b-norbornene functional PLA-b-P(α-BrCL), was constructed to covalently conjugate dual anticancer drugs, i.e., doxorubicin (DOX) and paclitaxel (PTX). The resultant P-PTX-DOX prodrugs were confirmed by 1H NMR and HPLC. By adjusting the length of PLA and PCL, it was shown that this polymer could carry relatively sufficient amount of both drugs (12.1 wt% of PTX and 15.8 wt% of DOX, respectively). Moreover, the drug release profile of P-PTX-DOX in vitro was also analyzed, which showed the desired drug release in a sustained manner. Cytotoxicity study indicated synergistic effects of P-PTX-DOX self-assembled micelles in suppression of proliferation of A549 cancer cells. In summary, a novel polyester-based copolymer was developed to covalently conjugate dual-drug, which exhibited controlled drug release behavior and synergistic anti-cancer efficacy in vitro.

Hydroxyapatite (HA)/nanotubular titanium dioxide (TiO2) composite coatings loaded with antibiotics were developed to combine biocompatibility and antibacterial property. TiO2 nanotubes were first fabricated on Ti plates using anodization techniques. Then HA nanocrystals were synthesized on the TiO2 nanotubes by electrochemical deposition, followed by loading of a model drug compound, streptomycin. The streptomycin release profile of the composite coating was investigated. Bacterial tests demonstrate that the streptomycin-loaded composite coatings were highly effective in inhibiting bacterial growth. Simulated body fluid (SBF) experiments indicated that the composite coatings possessed good osseointegration capability.

espanolEl presente estudio se propuso investigar los efectos de la pectina amidada de bajo metoxilo (ALM, 0.3%, p/v) en las propiedades fisicoquimicas y estructurales de las proteinas de suero polimerizadas (PWP, 10%, w/v) y preparadas mediante el metodo de agregacion termica a 85°C durante 10–30 min. Asimismo, en el estudio se analizaron: el tamano de las particulas, el potencial zeta, el punto isoelectrico, la hidrofobicidad superficial, el grupo sulfhidrilo libre, las propiedades reologicas y la estructura secundaria de todas las muestras. Se constato que la pectina ALM aumento el diametro medio y estrecho la distribucion de tamanos de las muestras de PWP (p EnglishThis study aimed to investigate effects of amidated low methoxyl (ALM, 0.3%, w/v) pectin on physiochemical and structural properties of polymerized whey proteins (PWP, 10%, w/v) prepared by thermal aggregation at 85°C for 10–30 min. Particle size, zeta potential, isoelectric point (IEP), surface hydrophobicity, free sulphydryl group, rheological properties and the secondary structure of all samples were analysed. ALM pectin increased mean diameter and narrowed size distribution of PWP samples (p

In this paper, we investigate the secure transmission in two-way untrusted amplify-and-forward relay networks with simultaneous wireless information and power transfer (SWIPT). Two secure SWIPT relaying strategies, namely, secure power splitting (SPS) and secure time switching (STS), are studied with the objective of secrecy rate (SR) and secure energy efficiency (SEE) maximization. First, the high signal-to-noise ratio approximations of SR and SEE are established, based on which non-convex SPS-based and convex STS-based SR maximization problems are formulated to jointly optimize the source transmit power and resource division ratio. Suboptimal solutions are obtained by employing Dinkelbach's method and Newton's method, respectively. Furthermore, to guarantee both the energy efficiency and secure quality of service (QoS) performance, SEE maximization problems are formulated with the consideration of the energy harvesting activation constraint and the target SR requirement. The intractable non-convex SEE maximization problems are reformulated as parameter programming, transformed to Lagrange dual problems, and finally solved by two SEE resource allocation algorithms with low complexity. Numerical results verify the convergence and effectiveness of the proposed algorithms and provide new insights into relaying strategy design and secure relay placement.

A novel resource utilization of the calcium-based semi-dry flue gas desulfurization ash is investigated. In the present study, the semi-dry desulfurization ash is used as a reductant for chromium and vanadium removal by chemical reduction precipitation, the byproduct gypsum and chromium-contained sludge are obtained. Besides, the effects of main operational parameters (reaction pH, desulfurization ash dosage and reaction time) on the heavy metal removal are investigated, and the main reaction mechanism for this treatment technology is also proposed. Under the optimal conditions, the residual concentrations of Cr(VI), total Cr and V are 0.163mg/L, 0.395mg/L and 0.155mg/L, respectively. Additionally, byproduct gypsum and chromium-contained sludge are characterized using X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope-energy dispersive spectrometer (SEM-EDS) and thermogravimetry differential scanning calorimetry (TG-DSC), respectively. Finally, the resource utilization methods of the byproduct gypsum and chromium-contained sludge from this technology are also submitted. The byproduct gypsum can be utilized to produce hemihydrate calcium sulfate whisker, and the roasted heavy metal precipitation can be used as a primary chromium raw material (Cr2O3 content is about 83%).

In the present study, a novel resource utilization method using wet magnesia flue gas desulfurization (FGD) residue for the simultaneous removal of ammonium nitrogen (NH4–N) and heavy metal pollutants from vanadium (V) industrial wastewater was proven to be viable and effective. In this process, the wet magnesia FGD residue could not only act as a reductant of hexavalent chromium [Cr(VI)] and pentavalent vanadium [V(V)], but also offered plenty of low cost magnesium ions to remove NH4–N using struvite crystallization. The optimum experimental conditions for Cr(VI) and V(V) reduction are as follows: the reduction pH = 2.5, the wet magnesia FGD residue dose is 42.5 g L−1, t = 15.0 min. The optimum experimental conditions for NH4–N and heavy metal pollutants removal are as follows: the precipitate pH = 9.5, the n(Mg2+) : n(NH4+) : n(PO43−) = 0.3 : 1.0 : 1.0, t = 20.0 min. Finally the NH4–N, V and Cr were separated from the vanadium containing industrial wastewater by forming the difficult to obtain, soluble coprecipitate containing struvite and heavy metal hydroxides. The residual pollutant concentrations in the wastewater were as follows: Cr(VI) was 0.047 mg L−1, total Cr was 0.1 mg L−1, V was 0.14 mg L−1, NH4–N was 176.2 mg L−1 (removal efficiency was about 94.5%) and phosphorus was 14.7 mg L−1.

Currently, the strategy of combining photodynamic therapy (PDT) and chemotherapy for enhancing cancer therapeutic efficiency has aroused extensive interest. Nonetheless, weaknesses such as low local concentration, uncontrollable release of the drug, a non-suitable treatment light source, and a low response to the tumor site of PDT lead to the combined treatment effect not being ideal. Herein, we proposed simple and intelligent ROS-responsive zinc phthalocyanine sensitized TiO2 nanoparticles which conjugated with chlorambucil (CBL) (mTiO2–BCBL@ZnPC NPs) in an attempt to solve these issues. Not only were the nanoparticles triggered in near infrared radiation (NIR) for PDT with various reactive oxygen species (ROS) being generated, but the nanoparticles also realized the controllable release of CBL by H2O2, a major kind of ROS, through cleavage of the phenylboronic ester between CBL and the nanoparticle. Impressively, the controllable release of CBL under NIR irradiation showed an on–off characteristic and time dependency. In addition, the well-defined mTiO2–BCBL@ZnPC NPs with a 30 nm average diameter showed good stability and biocompatibility. The in vitro cytotoxicity studies demonstrated that the mTiO2–BCBL@ZnPC NPs were more cytotoxic under NIR irradiation than the mTiO2@ZnPC NPs and CBL, while the mTiO2–BCBL@ZnPC NPs were less cytotoxic under dark conditions. The above results implied that photo-controlled drug release is a promising choice for cancer therapy due to its high selectivity, good safety and low side-effects, and would be expected to be used in chemo-photodynamic combined therapy for improving the therapeutic efficiency.

In this paper, we study the coverage probability and average data rate of user pairing in cooperative non-orthogonal multiple access (NOMA) networks. With fixed locations of the source and typical user, the candidate users for pairing follow homogeneous Poisson point process. Considering the geometric distance between nodes, close-to-user pairing (CUP) and close-to-source pairing (CSP) schemes are investigated with the near user acting as half-duplex relay or full-duplex (FD) relay. Lower bounds on the coverage probability and average data rate are approximately obtained using stochastic geometry and Gaussian-Chebyshev quadrature. Numerical and simulation results corroborate the accuracy of the analytical results and reveal that CUP-based cooperative NOMA outperforms CSP-based cooperative NOMA in terms of the data rate performance. With typical user close to the source, CUP-based FD NOMA is the best transmission scheme (among CUP-based and CSP-based cooperative NOMA, non-cooperative NOMA, and OMA schemes) that maximizes the sum data rate and the minimum user rate.

The recent advancement in intelligent transportation system makes it crucial to equip vehicles with intelligent onboard system (IOS). With the help of IOSs, vehicles can obtain varieties of convenient services from both remote service centers and other vehicles. However, the deficiency of the existing IOS makes the upgrade process complex and costly for the reason of its closed architecture. In order to solve this problem, network function virtualization (NFV) is introduced to make the IOS open by virtualizing services as software applications that can be executed on standard IT platforms. Furthermore, the NFV-based IOS can build an ordered service chain, consisting of virtualized network functions (VNFs), among different IOSs, and support VNF reuse. Thus, it is imperative to optimize the chaining scheme to obtain a shorter average service time (AST). In this paper, we propose a clustered VNF chaining scheme, which deploys VNFs in clusters according to the cluster head of each vehicle clusters, and derive the expression of the AST in a relative static scenario. Based on this scheme, the dynamic AST of a given cluster in a moving scenario is also analyzed on the grounds of both macroscopic mobility model and microscopic mobility model. The analyses show that both of the vehicle density and distance-headway variations have influence on the AST of one given cluster, which is verified by numerical results. In addition, the experiment results also show that the proposed scheme has a better performance compared with other two schemes, which reduces the AST 61% and 43%, respectively.

Human body microenvironment adaptive power generator with multifunction is attractive for the development of portable wearable devices. Here, a PEDOT-based photo-thermoelectric textile is developed via a two-step strategy, where the PDA is introduced to induce PEDOT to form the hierarchical structure. Thus, the top surface of the PEDOT-based textile owns the excellent thermoelectric performance (PF = 88.70 nW/(m•K2)), and the bottom surface holds a great photothermal effect that can reach about 80 °C under 175w IR light. In addition, the PEDOT-based textile has 51.87% of solar conversion efficiency under 3 sun. A assembled textile solar panel fabricated by the sewing method renders a voltage output of 1.37 mV under 500w illumination. Interestingly, with the synergistic work of photo-thermoelectric and hydroelectric effects, the wetted textile solar panel can produce a voltage of ~ 12.5 mV and a power of 9.81 μW under 500 W illumination. Meanwhile, it can also generate the solar steam of ~ 3 g within 1 h. Therefore, such wet textile solar panels can harvest solar energy and generate solar steam at the same time, which provides a route to fabricate a smart wearable energy harvester that can be used for human body humidity management.

Boron-containing compounds have been discovered as a kind of promising metal-free catalysts for oxidative dehydrogenation (ODH) of alkanes. Herein, we provide a simple method to synthesize a series of BCN catalysts with tunable carbon contents. We reveal that incorporating appropriate amounts of carbon into the hexagonal boron nitride (h-BN) structure can significantly increase the surface area and lead to remarkable enhanced catalytic conversion. The best-performing catalyst shows 82.3% propylene selectivity and 93.8% olefin selectivity at propane conversion of 18.5%. Systematic study indicates that the carbon doping can derive BN with a large number of defective sites, which are prone to form reactive boron-oxygen species during activation. The excess carbon inclusion, however, results in a decreased catalytic conversion, originated from catalyst decomposition and sintering. In situ transmission electron microscopy (TEM) performed under activation and catalytic reaction conditions shows the dynamic process of gas-phase induced structural/compositional transformations, providing direct insights into the origins of catalytic deactivation.

Converting solar energy into electricity is highly appealing for portable wearable devices. Herein, an facile low-temperature in situ interface polymerization is proposed to fabricate poly (3,4-ethylene dioxythiophene) (PEDOT)-based polyacrylonitrile (PAN) nanofiber film (PAN-PEDOT). Owing to the synergy of PEDOT and fabric light traps, the fabricated PAN-PEDOT owns excellent photo-thermoelectric performances with a power factor of ~256.61 nWm−1 k−2. Accordingly, a photo-thermoelectric harvester assembled by the optimum PAN-PEDOT strip and the copper wires reached a 0.17 mV voltage output under infrared (IR) light. Furthermore, a flexible textile solar panel assembled using the optimum PAN-PEDOT and the conductive nanofiber films were placed under an IR lamp and sunlight to investigate its performance in on-body applications. Results showed that the solar panel can obtain a voltage outputs of 1.39 mV and 0.56 mV and a power outputs of 0.37 nW and 0.06 nW under an IR lamp and sunlight, respectively. Therefore, the photo-thermoelectric fabric has high potential in solar-to-heat and solar-to-electricity applications.

Although axonal damage induces rapid changes in gene expression in primary sensory neurons, it remains unclear how this process is initiated. The transcription factor ATF3, one of the earliest genes responding to nerve injury, regulates expression of downstream genes that enable axon regeneration. By exploiting ATF3 reporter systems, we identify topoisomerase inhibitors as ATF3 inducers, including camptothecin. Camptothecin increases ATF3 expression and promotes neurite outgrowth in sensory neurons in vitro and enhances axonal regeneration after sciatic nerve crush in vivo. Given the action of topoisomerases in producing DNA breaks, we determine that they do occur immediately after nerve damage at the ATF3 gene locus in injured sensory neurons and are further increased after camptothecin exposure. Formation of DNA breaks in injured sensory neurons and enhancement of it pharmacologically may contribute to the initiation of those transcriptional changes required for peripheral nerve regeneration.

An integrated simple physical-chemical method was proposed to realize the comprehensive utilization of valuable resources from vanadium-extracted solution. The hazardous vanadium-extracted solution contains high concentrations of Cr(VI), ammonia nitrogen, sodium salt, and silicic acid. Firstly, a series of operations include reduction-precipitation, calcination, and leaching were used to recover high concentration Cr(VI), and 99.96% of Cr(VI) was recovered as chromium oxide with the purity of 97.24%. Optimum conditions for the reduction pH, amount of sodium sulfite, precipitation pH, and precipitation time were 2.0, 1.2 times theoretical, 7.3, and 15 min, respectively. Secondly, clean ammonia nitrogen recovery through waste heat distillation was realized. And the total recovery efficiency of ammonia nitrogen was 95.6% at pH = 11.0, distillation 50 min with 0.5M sulfuric acid as the absorption liquid. Also, the distillation residue sodium sulfate was concentrated and purified by distillation. Finally, all the resources were separated efficiently and could be reused back into the upstream vanadium extraction process, achieving resource recycling. Moreover, material balance, energy analysis and the flow chart of the near-zero-waste approach for resource recycling from the hazardous vanadium-extracted solution were concluded.

Cryptotanshinone is known as a quinoid diterpene extracted from the root of Salvia miotiorrhiza bunge and can show outstanding anticancer activities. In the present study, we explored the mechanism of action of cryptotanshinone, and its potential efficacy as a promising therapy for the treatment of non-small cell lung cancer (NSCLC) cell line (A549) in vitro. A549 cells were incubated with cryptotanshinone and cell proliferation and apoptosis were investigated using MTT, LDH, ROS, Annexin-V-FITC assays. The expression levels of lncRNA HOTAIR and p-Akt were quantified by quantitative real-time PCR (qPCR) and western blot, respectively. The results showed that cryptotanshinone mitigated cell proliferation in a dose and time-dependent manner through a significant increase in LDH release, ROS production, and apoptosis in A549 lung cancer cells. Treatment of A549 cells with cryptotanshinone also led to downregulation of lncRNA HOTAIR and protein level of p-Akt. Furthermore, the anticancer effect of cryptotanshinone was inhibited in the presence of NAC as a potential antioxidant. In general, it was found that cryptotanshinone is an effective agent in preventing lung cancer cells growth through downregulation of HOTAIR and p-Akt expression which is partially due to high level of ROS.

For the first time, the hierarchical structures of Li0.35Zn0.3Fe2.35O4(LZFO)/polyaniline nanocomposites were successfully synthesized by interfacial polymerization. Firstly, the LZFO particles were prepared by the sol–gel method, and subsequently the PANI nanorods, composed of nanoneedle-like PANI, were grafted on the surface of the LZFO. A novel microtopography, urchin-like, of LZFO/PANI was prepared by a simple, efficient and controllable two-step method. The crystal structure, chemical bonding states and morphology of samples were characterized by means of Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Scanning and Transmission electron microscopy (SEM/TEM). The bandwidth of reflection loss exceeds 10 dB in the frequency was 5.56 GHz (3.36–8.48, 10.32–10.76 GHz), and the maximum reflection loss can reach − 49.4 dB at 4.96 GHz with the thickness of 5.1 mm. The enhanced microwave absorption properties of LZFO/PANI nanocomposites are mainly ascribed to the multi-level structure and the improved impedance matching, and make it a potential candidate for microwave absorption materials.

Mina Yan, Chanzhen Yang, Binyao Huang, Zeqian Huang, Liangfeng Huang, Xuefei Zhang, Chunshun Zhao School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou Higher Education Mega Center, Guangzhou, China Abstract: Layered double hydroxide (LDH) nanoparticles are emerging as one of the promising nanomaterials for biomedical applications, but their systemic toxicity in vivo has received little attention. In the present study, the effects of inorganic nanoparticle aggregation on their systemic toxicity were examined. Remarkably, aggregation was observed after the mixing of naked LDH nanoparticles with saline or erythrocytes. Significant accumulation of the naked LDH nanoparticles in the lungs of mice was detected 1 h after intravenous administration, and the survival rate of mice was 0% after 6 repeated injections. Furthermore, flocculent precipitates in the alveoli and congestion in the lung interstitium were observed in the dead mice. However, lipid membrane-coated LDH nanoparticles would not form aggregates and could be injected intravenously >6 times without causing death. These findings suggested that repeated injections of LDH were lethal even at low dose (30 mg/kg), and lipid membrane coating can be considered as an approach for reducing this risk. Keywords: inorganic nanoparticles, aggregation, erythrocyte aggregation, repeated intravenous injection, pulmonary embolism, sudden death

Silver nanoparticles deposited on hydroxyapatite coatings (Ag-HA) by a two-stage electrochemical method were found to impart inconsistent antibacterial properties to the bioactive coatings. To test the hypothesis that oxidation of the silver nanoparticles would enhance antimicrobial activity, the coatings were heated in air at 170° C for 8 h. Following heat treatment, X-ray photoelectron spectroscopy confirmed the formation of silver oxide on the surface of the silver nanoparticles. The heat treatment did not cause any measurable change in the crystal structure of the coating as determined by X-ray diffraction. Bacterial culture tests revealed that the heated Ag-HA coatings were able to kill Escherichia coli (E. coli) more consistently than non-heated coatings. It is believed that silver nanoparticles in the heated Ag-HA coatings can release more Ag+ ions into the bacterial suspension, since Ag+ ions play a significant role in antibacterial activity. The heat treatment temperature of 170° C is high enough for dry heat sterilization protocols, yet low enough to allow hydroxyapatite crystals to remain stable. The heat treatment process therefore offers a simple technique to ensure consistent antimicrobial activity from the bioactive Ag-HA composite coatings.

Traditional chemotherapy strategy exists undesirable toxic side-effects to normal tissues due to the low selectively to cancer cells of micromolecule cytotoxic drugs. One considered method to realizing the targeted delivery and increasing the specificity to tumor tissues of the cytotoxic drug is to transporting and discharging it through an environment-sensitive mechanism. In this study, a novel enzyme-sensitive polymer-doxorubicin conjugate was designed to delivery chemotherapeutic drug in a tumor-specific behavior and selectively activated in tumor tissue. Briefly, doxorubicin (DOX) was conjugated to carboxyl-terminated 4-arm poly(ethylene glycol) through a tetrapeptide linker, alanine-alanine-asparagine-leucine (AANL), which was one of the substrates of legumain, an asparaginyl endopeptidase that was found presented in plants, mammals and also highly expressed in human tumor tissues. Hereinafter, the polymer-DOX conjugate was termed as 4-arm PEG-AANL-DOX. Dynamic laser scattering (DLS) and transmission electron microscopy (TEM) measurements indicated that the 4-arm PEG-AANL-DOX could self-assemble into micelles in aqueous solution. Drug release and in vitro cytotoxicity studies revealed that the 4-arm PEG-AANL-DOX could be cleaved by legumain. Ex vivo DOX fluorescence imaging measurements demonstrated that the 4-arm PEG-AANL-DOX had an improved tumor-targeting delivery as compared with the free DOX·HCl. In vivo studies on nude mice bearing MDA-MB-435 tumors revealed that the 4-arm PEG-AANL-DOX had a comparable anticancer efficacy with the free DOX·HCl but without DOX-related toxicities to normal tissues as measured by body weight change and histological assessments, indicating that the 4-arm PEG-AANL-DOX had an improved therapeutic index for cancer therapy. Statement of Significance Herein we describe the construction of a novel tumor environment-sensitive delivery system through the instruction of a legumain-cleavable linkage to a polymer-DOX conjugate (4-arm PEG-AANL-DOX). This particular design strategy allows for polymer-DOX conjugates to be delivered in a tumor-specific manner and selectively activable in tumor microenvironment so that it can combine the advantages of tumor-specific delivery and tumor intracellular microenvironment-triggered release systems.

In a cache-enabled D2D underlaid cellular network, cooperation of BS caching and D2D caching can further exploit the limited storage capacity and achieve more efficient wireless resource utilization. In this complex network scenario, the closed form expression for successful transmission probability is firstly derived using stochastic geometry, to measure the proportion of users satisfying the delay guarantee. On this basis, a cooperative caching placement problem is formulated to maximize the successful transmission probability. We prove it can be transformed equivalently into a biconvex problem and then a block coordinate descent based algorithm is proposed. Simulation results demonstrate the performance gain of the proposed cooperative caching placement.

Histone deacetylases (HDACs) are crucial for regulating chromatin activity, which plays a critical role in cell proliferation, differentiation, and apoptosis of various cancers. Therefore, HDAC inhibitors have been applied as effective therapeutic agents for cancer treatment. However, the expression profiles and regulatory mechanisms of histone deacetylases in lung cancer are not well understood. In the present study, aberrant high levels of HDAC5 were observed in non-small cell lung cancer (NSCLC) and further analysis indicated a negative relationship between HDAC5 and a tumor suppressor, miR‑589‑5p, in NSCLC specimens. Consistently, miR‑589‑5p reduced the expression of HDAC5 by targeting the 3'UTR of HDAC5 mRNA in NSCLC cells. Considering the loss of miR‑589‑5p in NSCLC, the methylation status of the miR-589 gene promoter was examined. The hypermethylation of the miR-589 gene promoter was more significant in NSCLC cells compared with lung epithelial cells, and methylation inhibition by 5-aza-2-deoxycytidine (5-Aza-dC) decreased HDAC5 expression. Furthermore, several downstream gene clusters of HDAC5 were studied in the present investigation. As a result, miR‑589‑5p/HDAC5 pathway was found to regulate a number of cell cycle and epithelial-mesenchymal transition (EMT)-related genes in NSCLC cells. In vitro and in vivo phenotype experiments revealed a critical role of miR‑589‑5p/HDAC5 pathway in the migration, invasion, and tumorigenicity of NSCLC cells. These findings demonstrate a novel mechanism for deregulation of HDAC5 in NSCLC and suggest that miR‑589‑5p/HDAC5 pathway may represent a new prognostic biomarker and therapeutic target against NSCLC.

Patupilone, an original natural anti-cancer agent, also known as epothilone B or Epo906, has shown promise for the treatment of a variety of cancers, however, the systematic side effects of patupilone significantly impaired its clinical translation. Herein, patupilone-loaded PLG-g-mPEG micelles were prepared. Patupilone was grafted to a poly(L-glutamic acid)-graft-methoxy-poly(ethylene glycol) (PLG-g-mPEG) by Steglich esterification reaction to give PLG-g-mPEG/Epo906 that could self-assemble to form patupilone-loaded micelles (Epo906-M). The Epo906-M was able to inhibit the proliferation of A549, MCF-7 cancer cells and BEAs-2B cells in vitro. For in vivo treatment of orthotopic xenograft tumor models (MCF-7), the Epo906-M exhibited higher tumor inhibition efficiency with lower side effects as compared with free Epo906. Seventeen percent of the body weight loss appeared in the group treated with free Epo906 of 0.25 mg kg−1, while the group treated with Epo906-M of 10 mg kg−1 showed less than ten pe...

The thermal behavior of cotton straw briquette (CSB), municipal solid waste (MSW), and their blends was investigated using a thermogravimetric analyzer under N2/O2 and CO2/O2 atmospheres at 20 °C/min from an ambient temperature to 1000 °C. The kinetics and synergistic interaction between MSW and CSB in the co-combustion process were evaluated. The results indicated that MSW blended with CSB improved the ignition and burnout characteristics of the blends, while decreasing the comprehensive combustion characteristics index. The suitable proportions of CSB were less than 60% and 40% separately under 80N2/20O2 and 80CO2/20O2 atmospheres, respectively. The inhibitory effect of CO2 induced burnout temperature and residual mass increased, and the high-temperature stage reaction varied. Kinetic analysis of the blends indicated that blending with CSB could promote MSW combustion in the first reaction stage, while the second and third decomposition stages were complicated because of the synergistic interaction between MSW and CSB in the co-combustion process. The nth order reaction model fit the mass loss of theca-combustion process for the blends very well.

Because of the peculiarity of the bone microstructure, the uptake of chemotherapeutics often happens at non-targeted sites, which induces side effects. In order to solve this problem, we designed a bone-targeting drug delivery system that can release drug exclusively in the nidus of the bone. Alendronate (ALN), which has a high ability to target to hydroxyapatite, was used to fabricate double ALN-conjugated poly (ethylene glycol) 2000 material (ALN-PEG2k-ALN). The ALN-PEG2k-ALN was characterized using 1H NMR and 31P NMR and FTIR. ALN-PEG2k-ALN-modified calcium phosphate nanoparticles (APA-CPNPs) with an ALN targeting moiety and hydrophilic poly (ethylene glycol) arms tiled on the surface was prepared for bone-targeted drug delivery. The distribution of ALN-PEG2k-ALN was tested by X-ray photoelectron spectroscopy. Isothermal titration calorimetry data indicated that similar to free ALN, both ALN-PEG2k-ALN and APA-CPNPs can bind to calcium ions. The bone-binding ability of APA-CPNPs was verified via ex vivo imaging of bone fragments. An in vitro release experiment demonstrated that APA-CPNPs can release drug faster in an acid environment than a neutral environment. Cell viability experiments indicated that blank APA-CPNPs possessed excellent biocompatibility with normal cells. Methotrexate (MTX) loaded APA-CPNPs have the same ability to inhibit cancer cells as free drug at high concentrations, while they are slightly weaker at low concentrations. All of these experiments verified the prospective application of APA-CPNPs as a bone-targeting drug delivery system.

Echinococcosis is a serious zoonotic parasitic disease that is highly endemic in Qinghai Province. The present study aimed to investigate the prevalence of echinococcosis among schoolchildren in Golog Tibetan Autonomous Prefecture to improve early diagnosis and treatment of patients and to provide information for echinococcosis prevention and control. A total of 11,260 schoolchildren from five counties (Maqin, Gander, Dari, Jiuzhi, and Banma) in Golog Tibetan Autonomous Prefecture, Qinghai Province, were screened for echinococcosis. Screening involved ultrasound imaging combined with serologic examination as an auxiliary diagnostic test. The prevalence of echinococcosis in the schoolchildren was 2.1% (235/11,260), with a rate of 0.8% for cystic echinococcosis (CE; 89/11,260) and 1.3% for alveolar echinococcosis (AE; 146/11,260). Additionally, one child had a mixed infection. The prevalence ranged between 1.1% and 4.1% among the five investigated counties, and was highest in Dari County (4.1%). The prevalence of echinococcosis was higher in girls than in boys and gradually increased with age. In addition, children with CE mainly had type 1 (CE1) and type 3 (CE3) lesions, and children with AE mainly had small-diameter calcified lesions, suggesting that they were in the early asymptomatic stage of echinococcosis. In conclusion, children of Golog Tibetan Autonomous Prefecture appear to exhibit the highest recorded prevalence of CE and AE globally. Ultrasound is useful for screening populations in regions where both CE and AE are endemic.

The combustion characteristics and kinetics of municipal solid waste and biomass briquette blend were investigated at different particle sizes using thermogravimetric analysis. For the comparison between N2/O2 and CO2/O2 atmospheres, the mole fraction of oxygen was 20% and effects of the heating rate on the blend combustion behavior were also evaluated. Results showed that, in the range of less than 270 μm, the most vigorous combustion occurred at a particle size of 150–180 μm, regardless of the heating rate. With the increase of the heating rate, the combustion intensity of the blend could be improved and the reaction process was influenced to some extent. The replacement of N2 with CO2 reduced the combustion reactivity and had a significant effect at the particle sizes of less than 106 μm. The maximum values of activation energy (E) occurred at 150–180 μm, which corresponded to the maximum comprehensive combustion characteristic index S. The E values under an 80CO2/20O2 atmosphere were close to those un...

BRAF mutations are known as oncogenic drivers of non-small cell lung cancer (NSCLC). BRAF inhibition has demonstrated anti-tumor activity in patients with BRAF V600E mutant NSCLC. Further molecular screening for novel BRAF thr599dup mutation is warranted. The novel BRAF Thr599dup gene mutation, for which the repeat amino acid-tyrosine is inserted between the 599th amino acid and the 600th amino acid in exon 15 of BRAF, was identified by next-generation sequencing (NGS) during routine clinical care in a lung carcinoma sample from an Asian never-smoker. Other putative driver alterations including EGFR, ALK were not found in that patient. BRAF Thr599dup gene mutation analysis was consistent with BRAF v600E gene mutation. Here we report a novel BRAF gene mutation with molecular characteristics consistent with those in BRAF-driven NSCLC. Our case expands the scope of BRAF gene mutations and provides broader molecular profiling for optimizing therapeutic options for patients with NSCLC. The new BRAF gene mutation has important clinical meaning for cancer patients.

Objectives RET fusions have been reported in 1–2% of lung adenocarcinomas, and represent an actionable target. Patients whose tumors possess RET fusion are associated with clinical benefit from the treatment with multi-kinase inhibitors such as cabozantinib and vandetanib. Further molecular screening for RET fusions is warranted. Novel KIF13A-RET fusion containing an intact RET kinase domain involving exons 1–18 of KIF13A and exons 12–20 of RET was identified in a lung cancer specimen from an 74-year-old Asian never smoker by next-generation sequencing (NGS) during clinical care. The patient was negative for EGFR, ALK, ROS1 and other putative driver alterations. Fusion analysis is consistent with other described RET fusions and is predicted to result in aberrant constitutive activation caused by dimerization and sensitivity to RET-directed therapies. We describe a novel RET-fusion with molecular characteristics consistent with RET-driven non-small cell lung cancer. Our case expands the spectrum of RET fusion partners and supports broad molecular profiling in non-small cell lung cancer optimizing patient therapeutic options. The new RET fusion has immediate clinical implications for cancer patients.