CircUBA2 promotes the cancer stem cell-like properties of gastric cancer through upregulating STC1 via sponging miR-144-5p.

BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.

A cryogenic on-chip microwave pulse generator for large-scale superconducting quantum computing.

For superconducting quantum processors, microwave signals are delivered to each qubit from room-temperature electronics to the cryogenic environment through coaxial cables. Limited by the heat load of cabling and the massive cost of electronics, such an architecture is not viable for millions of qubits required for fault-tolerant quantum computing. Monolithic integration of the control electronics and the qubits provides a promising solution, which, however, requires a coherent cryogenic microwave pulse generator that is compatible with superconducting quantum circuits. Here, we report such a signal source driven by digital-like signals, generating pulsed microwave emission with well-controlled phase, intensity, and frequency directly at millikelvin temperatures. We showcase high-fidelity readout of superconducting qubits with the microwave pulse generator. The device demonstrated here has a small footprint, negligible heat load, great flexibility to operate, and is fully compatible with today's superconducting quantum circuits, thus providing an enabling technology for large-scale superconducting quantum computers.

Increased ONECUT2 induced by Helicobacter pylori promotes gastric cancer cell stemness via an AKT-related pathway.

Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/ß-catenin phosphorylation. AKT/ß-catenin phosphorylation facilitates ß-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and ß-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/ß-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.

Lanthanide luminescence nanothermometer with working wavelength beyond 1500 nm for cerebrovascular temperature imaging in vivo.

Nanothermometers enable the detection of temperature changes at the microscopic scale, which is crucial for elucidating biological mechanisms and guiding treatment strategies. However, temperature monitoring of micron-scale structures in vivo using luminescent nanothermometers remains challenging, primarily due to the severe scattering effect of biological tissue that compromises the imaging resolution. Herein, a lanthanide luminescence nanothermometer with a working wavelength beyond 1500 nm is developed to achieve high-resolution temperature imaging in vivo. The energy transfer between lanthanide ions (Er3+ and Yb3+) and H2O molecules, called the environment quenching assisted downshifting process, is utilized to establish temperature-sensitive emissions at 1550 and 980 nm. Using an optimized thin active shell doped with Yb3+ ions, the nanothermometer's thermal sensitivity and the 1550 nm emission intensity are enhanced by modulating the environment quenching assisted downshifting process. Consequently, minimally invasive temperature imaging of the cerebrovascular system in mice with an imaging resolution of nearly 200 µm is achieved using the nanothermometer. This work points to a method for high-resolution temperature imaging of micron-level structures in vivo, potentially giving insights into research in temperature sensing, disease diagnosis, and treatment development.

CDK5 promotes apoptosis and attenuates chemoresistance in gastric cancer via E2F1 signaling.

BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.

Hydrogel platform capable of molecularly resolved pulling on cells for mechanotransduction.

The active forces exerted from the extracellular matrix (ECM) to mechanoreceptors have crucial impact on many cell functions and disease development. However, our understanding of the underlying mechanisms is held back due to the lack of ECM mimicking platform able to apply molecularly resolved forces to cells. Herein, we present novel hydrogel platform capable of generate pN range forces to specific cellular receptors, at molecular scale. This capability was achieved through near-infrared (NIR) light regulated macromolecular actuators functionalized within the platform. This platform enables us to reveal cell responses to molecularly resolved forces under controlled magnitude (150-400 â€‹pN) and frequency (up to 100 â€‹Hz) on matrix with varied stiffness. We find the stiffness of the matrix has a large influence on the applied force transduction to cells. This versatile platform holds the potential for establishing correlation between receptor signaling pathways and cellular responses closer to physiological conditions.

An ultra-high gain single-photon transistor in the microwave regime.

A photonic transistor that can switch or amplify an optical signal with a single gate photon requires strong non-linear interaction at the single-photon level. Circuit quantum electrodynamics provides great flexibility to generate such an interaction, and thus could serve as an effective platform to realize a high-performance single-photon transistor. Here we demonstrate such a photonic transistor in the microwave regime. Our device consists of two microwave cavities dispersively coupled to a superconducting qubit. A single gate photon imprints a phase shift on the qubit state through one cavity, and further shifts the resonance frequency of the other cavity. In this way, we realize a gain of the transistor up to 53.4 dB, with an extinction ratio better than 20 dB. Our device outperforms previous devices in the optical regime by several orders in terms of optical gain, which indicates a great potential for application in the field of microwave quantum photonics and quantum information processing.

A lanthanide nanocomposite with cross-relaxation enhanced near-infrared emissions as a ratiometric nanothermometer.

Lanthanide luminescence nanothermometers (LNTs) provide microscopic, highly sensitive, and visualizable optical signals for reporting temperature information, which is particularly useful in biomedicine to achieve precise diagnosis and therapy. However, LNTs with efficient emissions at the long-wavelength region of the second and the third near-infrared (NIR-II/III) biological window, which is more favourable for in vivo thermometry, are still limited. Herein, we present a lanthanide-doped nanocomposite with Tm3+ and Nd3+ ions as emitters working beyond 1200 nm to construct a dual ratiometric LNT. The cross-relaxation processes among lanthanide ions are employed to establish a strategy to enhance the NIR emissions of Tm3+ for bioimaging-based temperature detection in vivo. The dual ratiometric probes included in the nanocomposite have potential in monitoring the temperature difference and heat transfer at the nanoscale, which would be useful in modulating the heating operation more precisely during thermal therapy and other biomedical applications. This work not only provides a powerful tool for temperature sensing in vivo but also proposes a method to build high-efficiency NIR-II/III lanthanide luminescent nanomaterials for broader bio-applications.

Enhancing the Phosphate Adsorption of a Polyallylamine Resin in Alkaline Environments by Lanthanum Oxalate Modification.

Sevelamer hydrochloride (SH), originally developed as an oral pharmaceutical for controlling blood phosphate levels, is a polyallylamine resin that could be used in water treatments. Although it binds phosphates effectively, its adsorption capacity suffers from a significant loss at high pH. Here, we modify SH with lanthanum oxalate to improve its phosphate adsorption in alkaline environments. With less than 6.00 wt% in La content, the composite adsorbent (SH-1C-1La) exhibits an adsorption capacity of 109.3 mg P g-1 at pH 8.0 and 100.2 mg P g-1 at pH 10.0, demonstrating significant enhancement from the original SH (86.3 mg P g-1 at pH 8.0 and 69.4 mg P g-1 at pH 10.0). Besides its high adsorption capacity and rapid adsorption kinetics, SH-1C-1La is capable of maintaining more than 78% of its capacity after four regeneration cycles, showing good durability in long-term applications. Zeta-potential measurements and XPS analysis reveal that the lanthanum oxalate species increase the surface potential to enhance the electrostatic adsorption while introducing chemical binding sites for phosphate ions. Both factors lead to the improved adsorption properties. The modification by lanthanum oxalate species might provide a new alternative for improving the phosphate adsorption properties of anion-exchange resins.

Quantum-Memory-Enhanced Preparation of Nonlocal Graph States.

Graph states are an important class of multipartite entangled states. Previous experimental generation of graph states and in particular the Greenberger-Horne-Zeilinger (GHZ) states in linear optics quantum information schemes is subjected to an exponential decay in efficiency versus the system size, which limits its large-scale applications in quantum networks. Here, we demonstrate an efficient scheme to prepare graph states with only a polynomial overhead using long-lived atomic quantum memories. We generate atom-photon entangled states in two atomic ensembles asynchronously, retrieve the stored atomic excitations only when both sides succeed, and further project them into a four-photon GHZ state. We measure the fidelity of this GHZ state and further demonstrate its applications in the violation of Bell-type inequalities and in quantum cryptography. Our work demonstrates the prospect of efficient generation of multipartite entangled states in large-scale distributed systems with applications in quantum information processing and metrology.

A flying Schrödinger's cat in multipartite entangled states.

Schrödinger's cat originates from the famous thought experiment querying the counterintuitive quantum superposition of macroscopic objects. As a natural extension, several "cats" (quasi-classical objects) can be prepared into coherent quantum superposition states, which is known as multipartite cat states demonstrating quantum entanglement among macroscopically distinct objects. Here, we present a highly scalable approach to deterministically create flying multipartite Schrödinger's cat states by reflecting coherent-state photons from a microwave cavity containing a superconducting qubit. We perform full quantum state tomography on the cat states with up to four photonic modes and confirm the existence of quantum entanglement among them. We also witness the hybrid entanglement between discrete-variable states (the qubit) and continuous-variable states (the flying multipartite cat) through a joint quantum state tomography. Our work provides an enabling step for implementing a series of quantum metrology and quantum information processing protocols based on cat states.

Lanthanide Luminescent Nanocomposite for Non-Invasive Temperature Monitoring in Vivo.

Temperature monitoring in vivo plays a vital role in the investigation of biological processes of organisms and the improvement of disease theranostic methods. The development of lanthanide luminescent nanocomposite-derived temperature probes in vivo allows accurate and reliable interrogation of biological thermodynamic processes due to their superior photostability, high sensitivity, and non-invasive sensing fashion. This concept presented an overview of the recent development of lanthanide luminescent nanocomposite which are suitable for in vivo temperature monitoring, including the thermometric principles, key features, materials designs as well as their potential biomedical applications for non-invasive temperature detection in the living body. The perspectives of these lanthanide luminescent nanocomposite thermometers for the optimization of temperature monitoring performance and potential future development are also discussed.

On-Demand Storage and Retrieval of Microwave Photons Using a Superconducting Multiresonator Quantum Memory.

We realize on-demand storage and retrieval of weak coherent microwave photon pulses at the single-photon level. A superconducting multiresonator system which is composed of a set of frequency-tunable coplanar waveguide resonators is implemented as the quantum memory. By dynamically tuning the resonant frequencies of the resonators, we achieve tunable memory bandwidth from 10 to 55 MHz, with well preserved phase coherence. We further demonstrate on-demand storage and retrieval of a time-bin flying qubit. This result opens up a prospect to integrate our chip-based quantum memory with the state-of-the-art superconducting quantum circuit technology for quantum information processing.

Visible light photocatalytic properties of one-step SnO2-templated grown SnO2/SnS2heterostructure and SnS2nanoflakes.

The nanoflakes of SnS2/SnO2heterostructure and SnS2were synthesized by a one-step SnO2-templated chemical vapor deposition method. The metal oxide-assisted growth mechanism of SnS2/SnO2heterostructure and SnS2nanoflakes were realized through investigating serial microstructures of products with varied growth time. Furthermore, the photocatalytic activity for MB dyes degradation of varied growth time products was used to explore the effect of product microstructure under the visible light irradiation. The SnO2/SnS2heterostructure and the oxide vacancies of nanoflakes demonstrated an improved visible light photocatalytic performance for MB degradation, which was around twice of the pure SnS2nanoflakes and better than P25. The results of different scavengers on the degradation efficiency for MB indicate the·O2-, and ·OH are the main active species in the photodegradation reaction. The one-step growth mechanism of SnS2/SnO2could prove a facile process to grow metal oxide-metal sulfide heterostructure.

Highly Stretchable Room-Temperature Self-Healing Conductors Based on Wrinkled Graphene Films for Flexible Electronics.

Flexible conductors are emerging soft materials for diverse electrical applications. However, it still remains a great challenge to fabricate high-performance soft conductors that are highly conductive, largely stretchable, and rapid room-temperature self-healable. Here, we design and fabricate flexible conductive bilayer composite films composed of healable elastomeric substrates and wrinkled graphenes. The elastomeric substrates, obtained by a facile bulk copolymerization of N-isopropylacrylamide and 2-methoxyethyl acrylate, show fast room-temperature self-healing efficiency of up to 96%, imparted by the reversible hydrogen bonds. Importantly, the substrates also display strong interfacial adhesion crucial to the formation of stable bilayer composite films based on a prestrain route. The synergy between self-healing of the substrates and wrinkled structures of graphene is endowed to the composite films for mechanical and electrical healing. By adjusting the prestrain ratio of the substrates, the composite films could display the tunable stretchability, conductivity, and self-healing. The optimal bilayer composite film exhibits a high conductivity of 126 S cm-1, a large stretchability of 300%, and rapid room-temperature self-healing. Moreover, it is demonstrated that the composite films are strain-sensitive and can be used as strain sensors to monitor stretching deformation and human motion. These prominent demonstrations suggest a great potential of the bilayer composite films in next-generation wearable electronics.

Experimental entanglement of 25 individually accessible atomic quantum interfaces.

A quantum interface links the stationary qubits in a quantum memory with flying photonic qubits in optical transmission channels and constitutes a critical element for the future quantum internet. Entanglement of quantum interfaces is an important step for the realization of quantum networks. Through heralded detection of photon interference, we generate multipartite entanglement between 25 (or 9) individually addressable quantum interfaces in a multiplexed atomic quantum memory array and confirm genuine 22-partite (or 9-partite) entanglement. This experimental entanglement of a record-high number of individually addressable quantum interfaces makes an important step toward the realization of quantum networks, long-distance quantum communication, and multipartite quantum information processing.

Synthesis and characterization of energetic 3-nitro-1,2,4-oxadiazoles.

All new: 3-Nitro-5-guanidino-1,2,4-oxadiazole (NOG) was synthesized from diaminoglycoluril with in situ generated dimethyldioxirane (DMDO). The impact sensitivity of NOG is more than 40 J with a decomposition temperature of 290 °C. Some other energetic derivatives have been prepared and characterized.

A metal-free aerobic oxidation of nitrotoluenes catalyzed by N,N',N″-trihydroxyisocyanuric acid (THICA) and a novel approach to the catalyst.

A metal-free catalytic system with N,N',N″-trihydroxyisocyanuric acid (THICA) as the catalyst for the oxidation of nitrotoluenes is introduced, and a novel Pd-free approach for the synthesis of THICA was developed. In a solution of acetic acid, THICA and concentrated nitric acid, nitrotoluenes especially polynitrotoluenes such as 2,4,6-trinitrotoluene (TNT), were converted into the desired carboxylic acids under 0.2 MPa of O(2) at 100°C with yields up to 99%. THICA was synthesized from N-hydroxyphtalimide through a four-step synthesis in a total yield of 46%. A possible mechanism of this catalytic process was proposed where NO(2) and nitric acid first induced a radical of THICA, which then abstracts a hydrogen atom from the methyl on the aromatic ring to form a benzyl radical. This radical then initiates subsequent reactions. The production of the benzyl radical was supported by ESR measurements.

Intraocular gas associated pressure-induced interface keratopathy 8 years after laser in situ keratomileusis.

The authors report a clinically distinctive form of elevated intraocular pressure-induced interface keratopathy that occurred after a pars plana vitrectomy with intraocular gas tamponade for a macular hole in the right eye in a 35-year-old woman who had laser in situ keratomileusis in both eyes 8 years previously. The intraocular pressure was increased to 37 mm Hg after surgery. Diffuse lamellar keratitis-like interface infiltration was found with concurrent elevated intraocular pressure. The interface infiltration did not respond to steroids but resolved after the intraocular pressure was controlled. This case suggests that interface keratopathy is associated with increased intraocular pressure. Assessment of intraocular pressure is essential in patients presenting with interface keratopathy, especially in those who have undergone posterior segment operations with gas tamponade.

Quantitative optical coherence tomography findings in a 4-year-old boy with typical morning glory disk anomaly.

Morning glory disk anomaly (MGDA) is a congenital malformation of the optic disk that is usually unilateral. It has characteristic fundus findings, including enlarged optic disk opening and funnel-shaped excavation of the peripapillary fundus. Optical coherence tomography (OCT) with micrometer resolution and cross-sectional imaging capabilities can provide detailed information about the structure of the living eye. Some reports have used OCT to demonstrate the structure of the disk in older patients with MGDA but, to our knowledge, no quantitative OCT report concerning a child with MGDA has been published previously.