A von-Neumann-like photonic processor and its application in studying quantum signature of chaos.

Photonic quantum computation plays an important role and offers unique advantages. Two decades after the milestone work of Knill-Laflamme-Milburn, various architectures of photonic processors have been proposed, and quantum advantage over classical computers has also been demonstrated. It is now the opportune time to apply this technology to real-world applications. However, at current technology level, this aim is restricted by either programmability in bulk optics or loss in integrated optics for the existing architectures of processors, for which the resource cost is also a problem. Here we present a von-Neumann-like architecture based on temporal-mode encoding and looped structure on table, which is capable of multimode-universal programmability, resource-efficiency, phase-stability and software-scalability. In order to illustrate these merits, we execute two different programs with varying resource requirements on the same processor, to investigate quantum signature of chaos from two aspects: the signature behaviors exhibited in phase space (13 modes), and the Fermi golden rule which has not been experimentally studied in quantitative way before (26 modes). The maximal program contains an optical interferometer network with 1694 freely-adjustable phases. Considering current state-of-the-art, our architecture stands as the most promising candidate for real-world applications.

Resource-Efficient Direct Characterization of General Density Matrix.

Sequential weak measurements allow for the direct extraction of individual density-matrix elements, rather than relying on global reconstruction of the entire density matrix, which opens a new avenue for the characterization of quantum systems. Nevertheless, extending the sequential scheme to multiqudit quantum systems is challenging due to the requirement of multiple coupling processes for each qudit and the lack of appropriate precision evaluation. To address these issues, we propose a resource-efficient scheme (RES) that directly characterizes the density matrix of general multiqudit systems while optimizing measurements and establishing a feasible estimation analysis. In the RES, an efficient observable of the quantum system is constructed such that a single meter state coupled to each qudit is sufficient to extract the corresponding density-matrix element. An appropriate model based on the statistical distribution of errors is utilized to evaluate the precision and feasibility of the scheme. We have experimentally applied the RES to the direct characterization of general single-photon qutrit states and two-photon entangled states. The results show that the RES outperforms sequential schemes in terms of efficiency and precision in both weak- and strong-coupling scenarios. This Letter sheds new light on the practical characterization of large-scale quantum systems and the investigation of their nonclassical properties.

Controllable Carrier Doping in Two-Dimensional Materials Using Electron-Beam Irradiation and Scalable Oxide Dielectrics.

Two-dimensional (2D) materials, characterized by their atomically thin nature and exceptional properties, hold significant promise for future nano-electronic applications. The precise control of carrier density in these 2D materials is essential for enhancing performance and enabling complex device functionalities. In this study, we present an electron-beam (e-beam) doping approach to achieve controllable carrier doping effects in graphene and MoS2 field-effect transistors (FETs) by leveraging charge-trapping oxide dielectrics. By adding an atomic layer deposition (ALD)-grown Al2O3 dielectric layer on top of the SiO2/Si substrate, we demonstrate that controllable and reversible carrier doping effects can be effectively induced in graphene and MoS2 FETs through e-beam doping. This new device configuration establishes an oxide interface that enhances charge-trapping capabilities, enabling the effective induction of electron and hole doping beyond the SiO2 breakdown limit using high-energy e-beam irradiation. Importantly, these high doping effects exhibit non-volatility and robust stability in both vacuum and air environments for graphene FET devices. This methodology enhances carrier modulation capabilities in 2D materials and holds great potential for advancing the development of scalable 2D nano-devices.

Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/ß-catenin pathway under hypoxia.

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/ß-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/ß-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/ß-catenin pathway. CONCLUSION: JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/ß-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/ß-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.

Robust Threshold-Switching Behavior Assisted by Cu Migration in a Ferroionic CuInP2S6 Heterostructure.

The two-dimensional layered material CuInP2S6 (CIPS) has attracted significant research attention due to its nontrivial physical properties, including room-temperature ferroelectricity at the ultrathin limit and substantial ionic conductivity. Despite many efforts to control its ionic conductance and develop electronic devices, such as memristors, improving the stability of these devices remains a challenge. This work presents a highly stable threshold-switching device based on the Cu/CIPS/graphene heterostructure, achieved after a comprehensive investigation of the activation of Cu's ionic conductivity. The device exhibits exceptional threshold-switching performance, including good cycling endurance, a high on/off ratio of up to 104, low operation voltages, and an ultrasmall subthreshold swing of less than 1.8 mV/decade for the resistance-switching process. Through temperature-dependent electrical and Raman spectroscopy measurements, the stable resistive-switching mechanism is interpreted with a drifting and diffusion model of Cu ions under the electric field, rather than the conventional conducting filament mechanism. These results make the layered ferroionic CIPS material a promising candidate for information storage devices, demonstrating a compelling approach to achieving high-performance threshold-switching memristor devices.

Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3ß/ß-catenin pathway.

OBJECTIVE: Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness. METHODS: A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß)/ß-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3ß/ß-catenin signaling pathway was detected. RESULTS: Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3ß/ß-catenin signaling pathway. Additionally, the desmin+/CD31+ ratio, rather than the number of CD31+ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3ß/ß-catenin signaling pathway were also inhibited in cells treated with serum from swimming group. CONCLUSION: Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3ß/ß-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3ß/ß-catenin pathway. J Integr Med. 2023; 21(2): 184-193.

A universal programmable Gaussian boson sampler for drug discovery.

Gaussian boson sampling (GBS) has the potential to solve complex graph problems, such as clique finding, which is relevant to drug discovery tasks. However, realizing the full benefits of quantum enhancements requires large-scale quantum hardware with universal programmability. Here we have developed a time-bin-encoded GBS photonic quantum processor that is universal, programmable and software-scalable. Our processor features freely adjustable squeezing parameters and can implement arbitrary unitary operations with a programmable interferometer. Leveraging our processor, we successfully executed clique finding on a 32-node graph, achieving approximately twice the success probability compared to classical sampling. As proof of concept, we implemented a versatile quantum drug discovery platform using this GBS processor, enabling molecular docking and RNA-folding prediction tasks. Our work achieves GBS circuitry with its universal and programmable architecture, advancing GBS toward use in real-world applications.

Pulsed light power stabilization of a semiconductor laser using a mixed analog-digital method with an acousto-optic modulator.

Diffraction beams produced by an acousto-optic modulator are widely used in various optical experiments, some of which need to modulate the radio-frequency drive signal to change the diffraction beams from continuous light to pulsed light. The generation of such pulsed light is open-loop, and long-term stability of the power is disregarded. In this paper, we introduce a method to suppress the pulsed light power drift of a semiconductor laser. By using the servo system, the low frequency power drift of 1-60 kHz pulsed light can be suppressed. This pulsed light power stabilization method can be applied to optical rotation detection and pulse pumping.

Curcumolide reduces diabetic retinal vascular leukostasis and leakage partly via inhibition of the p38MAPK/NF-κ B signaling.

Retinal inflammation in a hyperglycemic condition is believed to play a crucial role in the development of diabetic retinopathy, and targeting inflammatory mediators is a promising strategy for the control of diabetic retinopathy. Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. In this study, we demonstrate that treatment with curcumolide alleviated retinal inflammatory activities both in vitro and in vivo in a STZ-induced diabetic rat model and in TNF-α-stimulated HUVECs. Curcumolide alleviated retinal vascular permeability and leukostasis and attenuated the overexpression of TNF-α and ICAM-1 in diabetic retinas. Moreover, curcumolide also inhibited inducible p38 MAPK and NF-κB activation and the subsequent induction of proinflammatory mediators. These data suggest potential treatment strategies against diabetic retinopathy, particularly in the early stages of the disease.