Memristors are emerging as a rising star of new computing and information storage techniques. However, the practical applications are severely challenged by their instability toward harsh conditions, ...including high moisture, high temperatures, fire, ionizing irradiation, and mechanical bending. In this work, for the first time, lead‐free double perovskite Cs2AgBiBr6 is utilized for environmentally robust memristors, enabling highly efficient information storage. The memory performance of the typical indium‐tin‐oxide/Cs2AgBiBr6/Au sandwich‐like memristors is retained after 1000 switching cycles, 105 s of reading, and 104 times of mechanical bending, comparable to other halide perovskite memristors. Most importantly, the memristive behavior remains robust in harsh environments, including humidity up to 80%, temperatures as high as 453 K, an alcohol burner flame for 10 s, and 60Co γ‐ray irradiation for a dosage of 5 × 105 rad (SI), which is not achieved by any other memristors and commercial flash memory techniques. The realization of an environmentally robust memristor from Cs2AgBiBr6 with a high memory performance will inspire further development of robust electronics using lead‐free double perovskites.
Double perovskite Cs2AgBiBr6 is fabricated into an indium tin oxide/Cs2AgBiBr6/Au device for the first time. Ultrastable memristive behavior is obtained owing to the tough crystallinity of Cs2AgBiBr6. Humidity‐, high temperature‐, fire‐, and radiation‐resistant properties of Cs2AgBiBr6‐based devices promote memristive devices to work in harsh environments, where most perovskite‐based devices may fail to work.
Memcapacitors are emerging as an attractive candidate for high‐density information storage due to their multilevel and adjustable capacitances and long‐term retention without a power supply. However, ...knowledge of their memcapacitive mechanism remains unclear and accounts for the limited implementation of memcapacitors for multilevel memory technologies. Here, repeatable and reproducible quaternary memories fabricated from hybrid perovskite (CH3NH3SnBr3) memcapacitors are reported. The device can be modulated to at least four capacitive states ranging from 0 to 169 pF with retention for 104 s. Impressively, an effective device yield approaching 100% for quaternary memory switching is achieved by a batch of devices; each state has a sufficiently narrow distribution that can be distinguished from the others and is superior to most multilevel memories that have a low device yield as well as an overlapping distribution of states. The memcapacitive switching stems from the modulated p–i–n junction capacitance triggered by Br− migration, as demonstrated by in situ element mapping, X‐ray photoelectron spectra, and frequency‐dependent capacitance measurements; this mechanism is different from the widely reported memristive switching involving filamentary conduction. The results provide a new way to produce high‐density information storage through memcapacitors.
An independent memcapacitor for quaternary memory is achieved. Four capacitive states, “OFF”, “ON1”, “ON2”, and “ON3”, are able to be repeatedly and reproducibly written/read/erased in an ITO/CH3NH3SnBr3/Au sandwich‐like device. The memcapacitive switching stems from Br– migration to modulate the p–i–n junction capacitance, which is different and independent from resistance switching in memristors.
Innovations in synthetic chemistry have a profound impact on the drug discovery process, and will always be a necessary driver of drug development. As a result, it is of significance to develop novel ...simple and effective synthetic installation of medicinal modules to promote drug discovery. Herein, we have developed a NaClO‐mediated cross installation of indoles and azoles, both of which are frequently encountered in drugs and natural products. This effective toolbox provides a convenient synthetic route to access a library of N‐linked 2‐(azol‐1‐yl) indole derivatives, and can be used for late‐stage modification of drugs, natural products and peptides. Moreover, biological screening of the library has revealed that several adducts showed promising anticancer activities against A549 and NCI‐H1975 cells, which give us a hit for anticancer drug discovery.
A rapid, effective NaClO‐mediated cross installation of indoles and azoles for the construction of various N‐linked 2‐(azol‐1‐yl) indole derivatives and the late‐stage functional modification of drugs and peptides has been developed, which can benefit anticancer hit discovery.
Despite the great advances in target therapy, lung cancer remains the top cause of cancer-related death worldwide. G protein-coupled receptor neurokinin-1 (NK1R) is shown to play multiple roles in ...various cancers; however, the pathological roles and clinical implication in lung cancer are unclarified. Here we identified NK1R as a significantly upregulated GPCR in the transcriptome and tissue array of human lung cancer samples, associated with advanced clinical stages and poor prognosis. Notably, NK1R is co-expressed with epidermal growth factor receptor (EGFR) in NSCLC patients' tissues and co-localized in the tumor cells. NK1R can crosstalk with EGFR by interacting with EGFR, transactivating EGFR phosphorylation and regulating the intracellular signaling of ERK1/2 and Akt. Activation of NK1R promotes the proliferation, colony formation, EMT, MMP2/14 expression, and migration of lung cancer cells. The inhibition of NK1R by selective antagonist aprepitant repressed cell proliferation and migration in vitro. Knockdown of NK1R significantly slowed down the tumor growth in nude mice. The sensitivity of lung cancer cells to gefitinib/osimertinib is highly increased in the presence of the selective NK1R antagonist aprepitant. Our data suggest that NK1R plays an important role in lung cancer development through EGFR signaling and the crosstalk between NK1R and EGFR may provide a potential therapeutic target for lung cancer treatment.
Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Gefitinib, an inhibitor of EGFR tyrosine kinase, is highly effective in treating NSCLC patients with activating EGFR ...mutations (L858R or Ex19del). However, despite excellent disease control with gefitinib therapy, innate resistance and inevitable acquired resistance represent immense challenges in NSCLC therapy. Gefitinib potently induces cytoprotective autophagy, which has been implied to contribute to both innate and acquired resistance to gefitinib in NSCLC cells. Currently, abrogation of autophagy is considered a promising strategy for NSCLC therapy. In the present study, YC-1, an inhibitor of HIF-1α, was first found to significantly inhibit the autophagy induced by gefitinib by disrupting the fusion of autophagosomes and lysosomes and thereby enhancing the proapoptotic effect of gefitinib in gefitinib-resistant NSCLC cells. Furthermore, the combinational anti-autophagic and pro-apoptotic effect of gefitinib and YC-1 was demonstrated to be associated with an enhanced of forkhead box protein O1 (FOXO1) transcriptional activity which resulted from an increase in the p-FOXO1 protein level in gefitinib-resistant NSCLC cells. Our data suggest that inhibition of autophagy by targeting FOXO1 may be a feasible therapeutic strategy to overcome both innate and acquired resistance to EGFR-TKIs.
Memristors are a new type of circuit element with a resistance that is tunable to discrete levels by a voltage/current and sustainable after removal of power, allowing for low‐power computation and ...multilevel information storage. Many organic‐inorganic lead perovskites are reported to demonstrate memristive behavior, but few have been considered for use as a multilevel memory; also, their potential application has been hindered by the toxicity of lead ions. In this article, lead‐free perovskite MASnBr3 was utilized in memristors for quaternary information storage. Indium tin oxide (ITO)/MASnBr3/Au memristors were fabricated and showed reliable memristive switching with well‐separated ON/OFF states of a maxima resistance ratio of 102 to 103. More importantly, four resistive states can be distinguished and repeatedly written/read/erased with a retention time of 104 seconds and an endurance of 104 pulses. By investigating the current‐electrode area relationship, Br distribution in the ON/OFF states by in situ Raman and scanning electron microscopy, and temperature‐dependent current decay, the memristive behavior was explicitly attributed to the forming/breaking of conductive filaments caused by the migration of Br− under an electric field. In addition, poly(ethylene terephthalate)‐ITO/MASnBr3/Au devices were found to retain their multiresistance state behavior after being bent for 1000 times, thus demonstrating good device flexibility. Our results will inspire more lead‐free perovskite work for multilevel information storage, as well as other memristor‐based electronics.
Lead‐free perovskite MASnBr3 was utilized in memristors for quaternary information storage. Four resistive states can be distinguished and repeatedly written/read/erased with a retention time of 104 seconds and an endurance of 104 pulses.
The widespread application of antiandrogen therapies has aroused a significant increase in the incidence of NEPC, a lethal form of the disease lacking efficient clinical treatments. Here we ...identified a cell surface receptor neurokinin-1 (NK1R) as a clinically relevant driver of treatment-related NEPC (tNEPC). NK1R expression increased in prostate cancer patients, particularly higher in metastatic prostate cancer and treatment-related NEPC, implying a relation with the progression from primary luminal adenocarcinoma toward NEPC. High NK1R level was clinically correlated with accelerated tumor recurrence and poor survival. Mechanical studies identified a regulatory element in the NK1R gene transcription ending region that was recognized by AR. AR inhibition enhanced the expression of NK1R, which mediated the PKCα-AURKA/N-Myc pathway in prostate cancer cells. Functional assays demonstrated that activation of NK1R promoted the NE transdifferentiation, cell proliferation, invasion, and enzalutamide resistance in prostate cancer cells. Targeting NK1R abrogated the NE transdifferentiation process and tumorigenicity in vitro and in vivo. These findings collectively characterized the role of NK1R in tNEPC progression and suggested NK1R as a potential therapeutic target.
As one of the candidates for the next generation of data storage techniques, organic multilevel resistive memory has attracted more and more attention. Even though many types of materials have been ...fabricated into memory devices and successfully obtained multilevel memory behaviors, they still suffer from complex fabrication processes, relatively expensive price and poor temperature stability, which hinders the further applications of RRAM techniques. On the other hand, many organics dyes with a conjugated zwitterion structure are commercially available and inexpensive but rarely considered as memory materials. Herein, two commercial dyes, Rhodamine B (Rh B) and Rhodamine 6G (R 6G), were selected as active materials to fabricate memory devices through a one-step method. The as-fabricated memory devices showed ternary write-once-read-many-times (WORM) type memory behaviors, with the retention time up to 5000 s. Benefitted from the strong intermolecular interactions, rhodamine-based memory devices could work stably under 80 °C. Additionally, Rh B and R 6G could also be fabricated on various flexible substrates, such as polyethylene terephthalate (PET), stamps and tree leaves. The ternary memory behaviors could be sustained after bending 1000 times. Our work demonstrates the potential of commercially available dyes for low price and easy-fabrication flexible multilevel resistive memories.
The fabricated Al/rhodamine/ITO devices showed ternary memory performance, and Rh B and R 6G could also be fabricated on various flexible substrates.
Wenshen ZhuanggLi formula （WSZG） is a traditional Chinese medicine used as an adjuvant for the prevention of bone metastases in breast cancer patients. In this study we investigated the efficacy of ...WSZG in preventing bone metastases and the potential mechanisms in a mouse xenograft model of breast cancer bone metastases. This model was established by injection of human MDA- MB-231BO-Luc breast cancer cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymat stem cells （BMSCs） into left ventricle of the heart in female nude mice. Then the mice were treated with WSZG （3.25, 6.5 or 13.0 mg-kEl.d1, ig） for four weeks, whereas zo{edronic acid （100 pg/kg per week, ig） was used as a positive control. The occurrence and development of bone metastases were monitored via bioluminescent imaging, and bone lesions were assessed using micro-CT. Intracardiac injection of the mixture of MDA-MB-231BO-Luc breast cancer cells with BMSCs significantly facilitated the bone metastatic capacity of the breast cancer cells, and aggravated bone lesions in the mouse xenograft model of breast cancer bone metastases. Administration of WSZG dose-dependently inhibited the incidence and intensity of bone metastases and protected against bone lesions by suppressing osteoclast formation and tumor cell infiltration. Furthermore, administration of WSZG caused a marked reduction in the expression of CCLS/CCR5 and IL-17B/IL-17BR in bone metastatic tissues. The results demonstrate thatWSZG exerts potential therapeutic effects in a mouse xenograft model of breast cancer bone metastases, which are partially mediated by weakening the interaction between BMSCs and breast cancer ceils in the tumor microenvironment.
AIM:To establish the rat model of streptozotocin(STZ)induced diabetic retinopathy(DR),which is the most common cause of visual loss and blindness in patients with diabetes,and observe the gene ...expression of vascular endothelial growth factor(VEGF) and its receptors during the development of DR.METHODS:A rat model of diabetes was established by intraperitoneal injection of STZ.The diabetic rats were housed for 2,3 and 4 months after the development of diabetes.Retinal histopathological observation was performed.The retinal vessels were observed by immunofluorescence staining by CD31.The mRNA expression of VEGF,VEGF receptor 1 and 2(VEGFR1/2) in rat retina was detected by reverse transcription polymerase chain reaction(RT-PCR) analysis. RESULTS:Retinal histopathological observation showed the morphological changes of inner nuclear layer(INL) and outer nuclear layer(ONL) at any time-point,and also demonstrated the increased new vessels at both 3,4 months after the development of diabetes.The CD31 staining results showed that the number of vessels was increased in the retinas of diabetic rats at both 3 and 4 months after the development of diabetes.As compared to the normal rats,the mRNA expression of VEGF was increased in retinas of diabetic rats at 3 months after the development of diabetes,while VEGFR1 and VEGFR2 mRNA expression was increased at 2,3 and 4 months after the development of diabetes.CONCLUSION:Takentogether,ourresultsdemonstrated that DR was occurred at 3 months after the development of diabetes,and the mRNA expression of VEGF,VEGFR1 and VEGFR2 were increased in the process of DR.The present study further evidenced the involvement of VEGF and its receptors in the process of DR.
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