Abstract The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to ...promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data. Expression of TWIST and HIF-1α proteins was significantly upregulated, whereas expression of E-cadherin and p16 was down-regulated in PDAC tissues compared to that of non-tumor tissues and in tumor tissues obtained from patients with tumor involving splenic artery than those without splenic artery involvement. Up-regulated TWIST in tumor tissues were associated with worse prognosis in PDAC patients. The in vitro data showed that HIF-1α-induced TWIST overexpression promoted tumor cell growth and EMT under a hypoxic condition via TWIST interaction with Ring1B and EZH2. In vivo data showed that TWIST overexpression or a hypoxic condition induce xenograft growth, abdominal metastasis and low mouse survival, whereas knockdown of either Ring1B or EZH2 expression suppressed tumor xenograft growth and metastasis and prolonged survival of nude mice. TWIST was the key player in promotion of pancreatic cancer development and metastasis under a hypoxic condition through interaction with Ring1B and EZH2 to regulate expression of E-cadherin and p16 proteins in pancreatic cancer cells.
Herein, interfacial engineering is demonstrated to improve the thermal stability of non‐fullerene bulk‐heterojunction (BHJ) OPVs to a practical level. An amphiphilic dendritic block copolymer (DBC) ...is developed through a facile coupling method and employed as the surface modifier of ZnO electron‐transporting layer in inverted OPVs. Besides showing distinct self‐assembly behavior, the synthesized DBC possesses high compatibility with plasmonic gold nanoparticles (NPs) due to the constituent malonamide and ethylene oxide units. The hybrid DBC@AuNPs interlayer is shown to improve device's performance from 14.0% to 15.4% because it enables better energy‐level alignment and improves interfacial compatibility at the ZnO/BHJ interface. Moreover, the DBC@AuNPs interlayer not only improves the interfacial thermal stability at the ZnO/BHJ interface but also endows a more ideal BHJ morphology with an enhanced thermal robustness. The derived device reserves 77% of initial PCE after thermal aging at 65 °C for 3000 h and yields an extended T80 lifetime of >1100 h when stored at a constant thermal condition at 65 °C, outperforming the control device. Finally, the device is evaluated to possess a T80 lifetime of over 1.79 years at room temperature (298 K) when stored in an inert condition, showing great potential for commercialization.
An amphiphilic dendritic block copolymer is developed to serve as an efficient surface modifier of ZnO electron‐transporting layer in an organic photovoltaic device. When using an interlayer based on its hybridization with gold nanoparticles, the device can deliver improved performance and possess a lifetime of over 1.79 years when stored at room temperature in inert conditions.
Herein, it is reported the influence of solution processing and treatments, such as adding marginal solvent, ultrasonication, and UV treatment, on the resulting perovskite (CsPbBr3) quantum dot ...(QD)/poly(3‐hexylthiophene) (P3HT) composite nanofibril films (CNFs) to improve the charge dissociation and photonic synaptic performance. A photonic synaptic transistor with CNFs can perform fundamental functions, including short‐term plasticity, long‐term plasticity, spike‐number‐dependent, and spike‐time‐dependent plasticity, to mimic sensing, computing, and memory functions. Notably, a synaptic device with CNFs presents an ultralow energy consumption of 0.18 fJ and zero‐gate operation. The superior performance of synaptic devices with CNFs can be attributed to two factors: (i) homogeneous axial distribution of the QDs and (ii) the formation of P3HT nanofibrils and co‐aggregates. Therefore, enhanced interfacial charge transfer between QDs and P3HT, ensuring decent carrier transport capability, is achieved. Collectively, the composite artificial synapse successfully provides an effective guide that offers a new perspective for the fabrication of one‐dimensional self‐assembled nanostructure‐based artificial synapses emulating human‐like memory, neuromorphic computing, and artificial intelligent systems.
Semiconducting self‐assembled composite nanostructures via solution processing is a promising strategy to improve the charge dissociation and photonic synaptic performance. In this study, quantum dot/poly(3‐hexylthiophene) nanofibrils are studied to understand the morphology/optoelectronic relation. The composite artificial synapse exhibits fundamental functions, including short‐term plasticity, long‐term plasticity, and spike‐number‐dependent and spike‐time‐dependent plasticity with ultralow energy consumption of 0.18 fJ and zero‐gate operation.
Developing high-performance electrocatalysts for hydrogen evolution reaction (HER) is crucial for sustainable hydrogen production, yet still challenging. Here, we report boron-modulated osmium (B-Os) ...aerogels with rich defects and ultra-fine diameter as a pH-universal HER electrocatalyst. The catalyst shows the small overpotentials of 12, 19, and 33 mV at a current density of 10 mA cm
in acidic, alkaline, and neutral electrolytes, respectively, as well as excellent stability, surpassing commercial Pt/C. Operando X-ray absorption spectroscopy shows that interventional interstitial B atoms can optimize the electron structure of B-Os aerogels and stabilize Os as active sites in an electron-deficient state under realistic working conditions, and simultaneously reveals the HER catalytic mechanisms of B-Os aerogels in pH-universal electrolytes. The density functional theory calculations also indicate introducing B atoms can tailor the electronic structure of Os, resulting in the reduced water dissociation energy and the improved adsorption/desorption behavior of hydrogen, which synergistically accelerate HER.
Pancreatic cancer (PC) represents a relatively rare but severe malignancy worldwide. Accumulated studies have emphasized the potential of long noncoding RNA (lncRNA) as therapeutic strategies for ...several human cancers. Thus, we aimed to investigate whether a novel non-coding RNA regulatory circuitry involved in PC. Aberrantly expressed lncRNAs and mRNAs were screened out of microarray database. Following the determination of RNA expression, PANC-1 and BxPC-3 PC cells were adopted, after which the expression of miR-330-5p, PAX8 and LINC00958 were subsequently altered. RNA crosstalk was validated by dual-luciferase reporter gene assay. In order to detect whether LINC00958 could act as ceRNA to competitively sponge miR-330-5p and regulate PAX8, subcellular location of LINC00958 and interaction between LINC00958 and miR-330-5p were measured by FISH and RNA pull down respectively. The epithelial mesenchymal transition (EMT) process, cell invasion, and tumor growth were determined in vitro and in vivo. LINC00958 and PAX8 were up-regulated, while miR-330-5p was down-regulated during PC. LINC00958 mainly expressed in the cytoplasm and LINC00958 competitively sponged miR-330-5p. Upregulated miR-330-5p or downregulated PAX8 inhibited the EMT process as well as the invasion and metastasis ability of the PC cells. Moreover, the results indicated that miR-330-5p negatively targeted PAX8, and LINC00958 ultimately showcasing its ability to bind to miR-330-5p through its interaction with AGO2. Therefore, silencing of LINC00958 may bind to miR-330-5p to inhibit PAX8 in a competitive fashion, thereby preventing the progression of PC.
•This study explores the effects of LINC00958 on PC via the miR-330-5p/PAX8 axis.•LINC00958 and PAX8 are highly expressed, yet miR-330-5p down-regulated in PC cells.•PAX8 is a target gene of miR-330-5p.•LINC00958 promotes PAX8 by binding with miR-330-5p in PC.•Down-regulated LINC00958 inhibits EMT, invasion, and metastasis of PC cells.
Polymer memristors with light weight and mechanical flexibility are preeminent candidates for low-power edge computing paradigms. However, the structural inhomogeneity of most polymers usually leads ...to random resistive switching characteristics, which lowers the production yield and reliability of nanoscale devices. In this contribution, we report that by adopting the two-dimensional conjugation strategy, a record high 90% production yield of polymer memristors has been achieved with miniaturization and low power potentials. By constructing coplanar macromolecules with 2D conjugated thiophene derivatives to enhance the π-π stacking and crystallinity of the thin film, homogeneous switching takes place across the entire polymer layer, with fast responses in 32 ns, D2D variation down to 3.16% ~ 8.29%, production yield approaching 90%, and scalability into 100 nm scale with tiny power consumption of ~ 10
J/bit. The polymer memristor array is capable of acting as both the arithmetic-logic element and multiply-accumulate accelerator for neuromorphic computing tasks.
Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As ...interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.
Maslinic acid (MA) could prevent IL‐1β‐associated inflammation as well as extracellular matrix (ECM) degradation in human osteoarthritis (OA) chondrocytes. The potential mechanism involved in the protective effect of MA was that it could reverse inflammation‐related destruction via inhibiting PI3K/AKT/NF‐κB pathways activation. MA ameliorates OA progression in vivo via inhibiting the devastation of cartilage surface, cartilage calcification, and osteophytes formation.
Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying ...mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real‐world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process.
A novel approach for using conjugated rod–coil materials as a floating gate in the fabrication of nonvolatile photonic transistor memory devices, consisting of n‐type Sol‐PDI and p‐type C10‐DNTT, is ...presented. Sol‐PDI and C10‐DNTT are used as dual functions of charge‐trapping (conjugated rod) and tunneling (insulating coil), while n‐type BPE‐PDI and p‐type DNTT are employed as the corresponding transporting layers. By using the same conjugated rod in the memory layer and transporting channel with a self‐assembled structure, both n‐type and p‐type memory devices exhibit a fast response, a high current contrast between “Photo‐On” and “Electrical‐Off” bistable states over 105, and an extremely low programing driving force of 0.1 V. The fabricated photon‐driven memory devices exhibit a quick response to different wavelengths of light and a broadband light response that highlight their promising potential for light‐recorder and synaptic device applications.
High‐performance photonic transistor memory devices are fabricated using conjugated rod–coil materials as a photoactive floating gate, in which the conjugated rods and side‐chain coils act as charge‐trapping and tunneling moieties, respectively. By inheriting their self‐assembled structure, both n‐type and p‐type memory devices exhibit a fast response, a current contrast over 105, and an extremely low programing driving force of 0.1 V.
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