The generation of ammonia, hydrogen production, and nitrogen purification are considered as energy intensive processes accompanied with large amounts of CO2 emission. An electrochemical method ...assisted by photoenergy is widely utilized for the chemical energy conversion. In this work, earth‐abundant iron pyrite (FeS2) nanocrystals grown on carbon fiber paper (FeS2/CFP) are found to be an electrochemical and photoactive catalyst for nitrogen reduction reaction under ambient temperature and pressure. The electrochemical results reveal that FeS2/CFP achieves a high Faradaic efficiency (FE) of ≈14.14% and NH3 yield rate of ≈0.096 µg min−1 at −0.6 V versus RHE electrode in 0.25 m LiClO4. During the electrochemical catalytic reaction, the crystal structure of FeS2/CFP remains in the cubic pyrite phase, as analyzed by in situ X‐ray diffraction measurements. With near‐infrared laser irradiation (808 nm), the NH3 yield rate of the FeS2/CFP catalyst can be slightly improved to 0.1 µg min−1 with high FE of 14.57%. Furthermore, density functional theory calculations demonstrate that the N2 molecule has strong chemical adsorption energy on the iron atom of FeS2. Overall, iron pyrite‐based materials have proven to be a potential electrocatalyst with photoactive behavior for ammonia production in practical applications.
Earth‐abundant iron pyrite nanocrystals grown on carbon fiber paper (FeS2/CFP) exhibit a good electrocatalytic performance for nitrogen reduction reaction with a high Faradaic efficiency (FE) ≈14.14%. With NIR laser irradiation (808 nm), the NH3 yield rate of FeS2/CFP catalyst can be improved to 0.1 µg min−1 with high FE of 14.57%.
Colorectal cancer (CRC) is a highly prevailing cancer and the fourth leading cause of cancer mortality worldwide. Aberrant expression of antiapoptotic BCL-2 family proteins is closely linked to ...neoplastic progression and chemoresistance. Obatoclax is a clinically developed drug, which binds antiapoptotic BCL-2, BCL-xL, and MCL-1 for inhibition to elicit apoptosis. Survivin is an antiapoptotic protein, whose upregulation correlates with pathogenesis, therapeutic resistance, and poor prognosis in CRC. Herein, we provide the first evidence delineating the functional linkage between Obatoclax and survivin in the context of human CRC cells. In detail, Obatoclax was found to markedly downregulate survivin. This downregulation was mainly achieved via transcriptional repression, as Obatoclax lowered the levels of both
mRNA and promoter activity, while blocking proteasomal degradation failed to prevent survivin from downregulation by Obatoclax. Notably, ectopic survivin expression curtailed Obatoclax-induced apoptosis and cytotoxicity, confirming an essential role of survivin downregulation in Obatoclax-elicited anti-CRC effect. Moreover, Obatoclax was found to repress hyperactive WNT/β-catenin signaling activity commonly present in human CRC cells, and, markedly, ectopic expression of dominant-active β-catenin mutant rescued the levels of survivin along with elevated cell viability. We further revealed that, depending on the cell context, Obatoclax suppresses WNT/β-catenin signaling in HCT 116 cells likely via inducing β-catenin destabilization, or by downregulating LEF1 in DLD-1 cells. Collectively, we for the first time define survivin downregulation as a novel, pro-apoptotic mechanism of Obatoclax as a consequence of Obatocalx acting as an antagonist to WNT/β-catenin signaling.
von Neumann architecture based computers isolate computation and storage (i.e. data is shuttled between computation blocks (processor) and memory blocks). The to-and-fro movement of data leads to a ...fundamental limitation of modern computers, known as the Memory wall. Logic in-Memory (LIM)/In-Memory Computing (IMC) approaches aim to address this bottleneck by directly computing inside memory units thereby eliminating energy-intensive and time-consuming data movement. Several recent works in literature, propose realization of logic function(s) directly using arrays of emerging resistive memory devices (example- memristors, RRAM/ReRAM, PCM, CBRAM, OxRAM, STT-MRAM etc.), rather than using conventional transistors for computing. The logic/embedded-side of digital systems (like processors, micro-controllers) can greatly benefit from such LIM realizations. However, the pure storage-side of digital systems (example SSDs, enterprise storage etc.) will not benefit much from such LIM approaches as when memory arrays are used for logic they lose their core functionality of storage. Thus, there is the need for an approach complementary to existing LIM techniques, that's more beneficial for the storage-side of digital systems; one that gives compute capability to memory arrays not at the cost of their existing stored states. Fundamentally, this would require memory nanodevice arrays that are capable of storing and computing simultaneously. In this paper, we propose a novel 'Simultaneous Logic in-Memory' (SLIM) methodology which is complementary to existing LIM approaches in literature. Through extensive experiments we demonstrate novel SLIM bitcells (1T-1R/2T-1R) comprising non-filamentary bilayer analog OxRAM devices with NMOS transistors. Proposed bitcells are capable of implementing both Memory and Logic operations simultaneously. Detailed programming scheme, array level implementation, and controller architecture are also proposed. Furthermore, to study the impact of proposed SLIM approach for real-world implementations, we performed analysis for two applications: (i) Sobel Edge Detection, and (ii) Binary Neural Network- Multi layer Perceptron (BNN-MLP). By performing all computations in SLIM bitcell array, huge Energy Delay Product (EDP) savings of ≈75× for 1T-1R (≈40× for 2T-1R) SLIM bitcell were observed for edge-detection application while EDP savings of ≈3.5× for 1T-1R (≈1.6× for 2T-1R) SLIM bitcell were observed for BNN-MLP application respectively, in comparison to conventional computing. EDP savings owing to reduction in data transfer between CPU ↔ memory is observed to be ≈780× (for both SLIM bitcells).
This paper tests the hypothesis that the commentary trend of the
Shen Nong Ben Cao Jing
(
Shen Nong’s Classic of the Materia Medica
) arises alongside the fashionable philology of the time, or the ...aversion against the Jin-Yuan medical philosophy. After surveying 12 major commentaries, it is concluded that the situation is more complicated than a simple assertion. The seemingly opposite philosophy and philology approaches have been used eclectically to innovate the understanding of ancient traditional Chinese medicine texts.
Melanoma is the most lethal skin malignancy. Fucoxanthin is a marine carotenoid with significant anticancer activities. Intriguingly, Fucoxanthin's impact on human melanoma remains elusive. Signal ...Transducer and Activator of Transcription 3 (STAT3) represents a promising target in cancer therapy due to its persistent activation in various cancers, including melanoma. Herein, we revealed that Fucoxanthin is cytotoxic to human melanoma cell lines A2758 and A375 while showing limited cytotoxicity to normal human melanocytes. Apoptosis is a primary reason for Fucoxanthin's melanoma cytotoxicity, as the pan‐caspase inhibitor z‐VAD‐fmk drastically abrogated Fucoxanthin‐elicited clonogenicity blockage. Besides, Fucoxanthin downregulated tyrosine 705‐phosphorylated STAT3 (p‐STAT3 (Y705)), either inherently present in melanoma cells or inducible by interleukin 6 (IL‐6) stimulation. Notably, ectopic expression of STAT3‐C, a dominant‐active STAT3 mutant, abolished Fucoxanthin‐elicited melanoma cell apoptosis and clonogenicity inhibition, supporting the pivotal role of STAT3 blockage in Fucoxanthin's melanoma cytotoxicity. Moreover, Fucoxanthin lowered BCL‐xL levels by blocking STAT3 activation, while ectopic BCL‐xL expression rescued melanoma cells from Fucoxanthin‐induced killing. Lastly, Fucoxanthin was found to diminish the levels of JAK2 with dual phosphorylation at tyrosine residues 1007 and 1008 in melanoma cells, suggesting that Fucoxanthin impairs STAT3 signaling by blocking JAK2 activation. Collectively, we present the first evidence that Fucoxanthin is cytotoxic selectively against human melanoma cells while sparing normal melanocytes. Mechanistically, Fucoxanthin targets the JAK2/STAT3/BCL‐xL antiapoptotic axis to provoke melanoma cell death. This discovery implicates the potential application of Fucoxanthin as a chemopreventive or therapeutic strategy for melanoma management.
Photocatalytic water splitting is a key technology for long-term hydrogen evolution with low environmental impact. In this work, an environment-friendly photocatalyst consisting of FeS2–TiO2 ...heterostructured nanocrystals has been successfully prepared by wet chemical synthesis for enhancing the photocatalytic hydrogen production rate over a wide range of absorption wavelengths. Its absorption range has been extended from the ultraviolet–visible to near-infrared (NIR) spectrum. The results of ultrafast optical spectroscopy suggest that charge transfer occurs between the FeS2 and TiO2 interface under NIR pulsed laser irradiation (800 nm). The highest photocatalytic hydrogen production rate of the FeS2–TiO2 heterostructure has been obtained in comparison with FeS2 nanocrystals (NCs) and TiO2 nanoparticles (NPs) under irradiation by a mercury arc lamp or a xenon lamp. In the FeS2–TiO2 heterostructure, the FeS2 NCs as a light harvester can efficiently absorb visible and NIR light to generate much more photoelectrons than TiO2 NPs only for hydrogen production. For long-term photocatalytic hydrogen production, the FeS2–TiO2 heterostructures also reveal an outstanding durability over 40 h. Overall, the FeS2–TiO2 heterostructure shows potential to be a TiO2-based photocatalyst for clean hydrogen production in practical applications.
Bladder cancer is the leading urinary tract malignancy. Epidemiological evidence has linked lower cancer incidence in schizophrenia patients to long-term medication, highlighting the anticancer ...potential of antipsychotics. Sertindole is an atypical antipsychotic agent with reported anticancer action on breast and gastric cancers. Yet, sertindole's effect on bladder cancer remains unaddressed. We herein present the first evidence of sertindole's antiproliferative effect and mechanisms of action on human bladder cancer cells. Sertindole was cytotoxic against bladder cancer cells while less cytotoxic to normal urothelial cells. Apoptosis was a primary cause of sertindole's cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk rescued cells from sertindole-induced killing. Mechanistically, sertindole inhibited the activation of signal transducer and activator of transcription 3 (STAT3), an oncogenic driver of bladder cancer, as sertindole lowered the levels of tyrosine 705-phosphorylated STAT3 along with that of STAT3's target gene BCL-xL. Notably, ectopic expression of the dominant-active STAT3 mutant impaired sertindole-induced apoptosis in addition to restoring BCL-xL expression. Moreover, bladder cancer cells overexpressing BCL-xL were refractory to sertindole's proapoptotic action, arguing that sertindole represses STAT3 to downregulate BCL-xL, culminating in the induction of apoptosis. Overall, the current study indicated sertindole exerts bladder cancer cytotoxicity by provoking apoptosis through targeted inhibition of the antiapoptotic STAT3/BCL-xL signaling axis. These findings implicate the potential to repurpose sertindole as a therapeutic strategy for bladder cancer.
Emerging non-volatile memory technologies are promising due to their anticipated capacity benefits, non-volatility, and zero idle energy. One of the most promising candidates is resistive random ...access memory (RRAM) based on resistive switching (RS). This paper reviews the development of RS device technology including the fundamental physics, material engineering, three-dimension (3D) integration, and bottom-up fabrication. The device operation, physical mechanisms for resistive switching, reliability metrics, and memory cell selector candidates are summarized from the recent advancement in both industry and academia. Options for 3D memory array architectures are presented for the mass storage application. Finally, the potential application of bottom-up fabrication approaches for effective manufacturing is introduced.
Bisphenol A (BPA) is an estrogen‐like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA ...residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE‐19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE‐19 cells. After BPA treatment, the expression of Bcl‐XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase‐9 to promote downstream caspase‐3 leading to cytotoxicity. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and heme oxygenase 1 (HO‐1) pathway play a major role in age‐related macular degeneration. Our results showed that expression of HO‐1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP‐activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA‐induced ROS generation and cytotoxicity were reduced by N‐acetyl‐l‐cysteine. Taken together, these results suggest that BPA induced ARPE‐19 cells via oxidative stress, which was associated with down regulated Nrf2/HO‐1 pathway, and the mitochondria dependent apoptotic signaling pathway.
Asymmetric nonlinear weight update is considered as one of the major obstacles for realizing hardware neural networks based on analog resistive synapses, because it significantly compromises the ...online training capability. This paper provides new solutions to this critical issue through co-optimization with the hardware-applicable deep-learning algorithms. New insights on engineering activation functions and a threshold weight update scheme effectively suppress the undesirable training noise induced by inaccurate weight update. We successfully trained a two-layer perceptron network online and improved the classification accuracy of MNIST handwritten digit data set to 87.8%/94.8% by using 6-/8-b analog synapses, respectively, with extremely high asymmetric nonlinearity.
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