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p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer.

Mammalian sirtuin 1 (SIRT1) has connected to an ever widening circle of activities that encompass cellular stress resistance, energy metabolism and tumorigenesis. However, underlying mechanisms leading to oncogenic SIRT1 overexpression are less understood. In this study, we identified SIRT1 regulatory microRNA (miRNA) and its function in hepatocellular carcinoma (HCC). Aberrant SIRT1 overexpression was demonstrated in a subset of human HCCs. SIRT1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. This led to hypophosphorylation of pRb, which inactivated E2F/DP1 target gene transcription, and thereby caused significant increase of HCC cells to remain in the G1/S phase. A comprehensive miRNA profiling analysis indentified five putative endogenous miRNAs that are significantly downregulated in HCC. Ectopic expression of miRNA mimics evidenced miR-29c to suppress SIRT1 in HCC cells. Notably, ectopic miR-29c expression repressed cancer cell growth and proliferation, and it recapitulated SIRT1 knockdown effects in HCC cells. In addition, miR-29c expression was downregulated in a large cohort of HCC patients, and low expression of miR-29c was significantly associated with poor prognosis of HCC patients. Taken together, we demonstrated that miR-29c suppresses oncogenic SIRT1 by way of binding to 3′-untranslated region of SIRT1 mRNA causing translational inhibition in liver cancer cells. The loss or suppression of miR-29c may cause aberrant SIRT1 overexpression and promotes liver tumorigenesis. Overall, we suggest that miR-29c functions as a tumor suppressor by regulating abnormal SIRT1 activity in liver.

A number of current approaches to quantum and neuromorphic computing use superconductors as the basis of their platform or as a measurement component, and will need to operate at cryogenic temperatures. Semiconductor systems are typically proposed as a top-level control in these architectures, with low-temperature passive components and intermediary superconducting electronics acting as the direct interface to the lowest-temperature stages. The architectures, therefore, require a low-power superconductor/semiconductor interface, which is not currently available. Here we report a superconducting switch that is capable of translating low-voltage superconducting inputs directly into semiconductor-compatible (above 1,000 mV) outputs at kelvin-scale temperatures (1 K or 4 K). To illustrate the capabilities in interfacing superconductors and semiconductors, we use it to drive a light-emitting diode in a photonic integrated circuit, generating photons at 1 K from a low-voltage input and detecting them with an on-chip superconducting single-photon detector. We also characterize our device’s timing response (less than 300 ps turn-on, 15 ns turn-off), output impedance (greater than 1 MΩ) and energy requirements (0.18 fJ m −2 , 3.24 mV nW −1 ). A superconducting switch that is capable of translating low-voltage superconducting inputs directly into semiconductor-compatible outputs at kelvin-scale temperatures could provide a superconductor-to-semiconductor logical interface for future quantum and neuromorphic computing architectures.

There are both fundamental and practical motivations for studying whether quantum entanglement can exist in macroscopic systems. However, multiparty entanglement is generally fragile and difficult to quantify. Dicke states are multiparty entangled states where a single excitation is delocalized over many systems. Building on previous work on quantum memories for photons, we create a Dicke state in a solid by storing a single photon in a crystal that contains many large atomic ensembles with distinct resonance frequencies. The photon is re-emitted at a well-defined time due to an interference effect analogous to multi-slit diffraction. We derive a lower bound for the number of entangled ensembles based on the contrast of the interference and the single-photon character of the input, and we experimentally demonstrate entanglement between over two hundred ensembles, each containing a billion atoms. We also illustrate the fact that each individual ensemble contains further entanglement.

Novel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor-initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy.

A missense somatic mutation in JAK2 gene ( JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly suggesting its role in the pathogenesis of myeloid disorders. As activation of JAK2 signaling is occurred in other malignancies as well, we have analysed 558 tissues from common human cancers, including colon, breast and lung carcinomas, and 143 acute adulthood leukemias by polymerase chain reaction – single strand conformation polymorphism analysis. We found three JAK2 mutations in the 113 acute myelogenous leukemias (AMLs) (2.7%), but none in other cancers. The mutations consisted of two V617F mutations and one K607N mutation. None of the AML patients with the JAK2 V617F mutation had a history of previous hematologic disorders. This is the first report on the JAK2 gene mutation in AML, and the data indicated that the JAK2 gene mutation may not only contribute to the development of chronic myeloid disorders, but also to some AMLs.

For the past 50 years, superconducting detectors have offered exceptional sensitivity and speed for detecting faint electromagnetic signals in a wide range of applications. These detectors operate at very low temperatures and generate a minimum of excess noise, making them ideal for testing the non-local nature of reality 1 , 2 , investigating dark matter 3 , 4 , mapping the early universe 5 – 7 and performing quantum computation 8 – 10 and communication 11 – 14 . Despite their appealing properties, however, there are at present no large-scale superconducting cameras—even the largest demonstrations have never exceeded 20,000 pixels 15 . This is especially true for superconducting nanowire single-photon detectors (SNSPDs) 16 – 18 . These detectors have been demonstrated with system detection efficiencies of 98.0% (ref.  19 ), sub-3-ps timing jitter 20 , sensitivity from the ultraviolet 21 to the mid-infrared 22 and microhertz dark-count rates 3 , but have never achieved an array size larger than a kilopixel 23 , 24 . Here we report on the development of a 400,000-pixel SNSPD camera, a factor of 400 improvement over the state of the art. The array spanned an area of 4 × 2.5 mm with 5 × 5-μm resolution, reached unity quantum efficiency at wavelengths of 370 nm and 635 nm, counted at a rate of 1.1 × 10 5  counts per second (cps) and had a dark-count rate of 1.0 × 10 −4  cps per detector (corresponding to 0.13 cps over the whole array). The imaging area contains no ancillary circuitry and the architecture is scalable well beyond the present demonstration, paving the way for large-format superconducting cameras with near-unity detection efficiencies across a wide range of the electromagnetic spectrum. The development of a 400,000-pixel superconducting nanowire single-photon detector array is described, improving the current state of the art by a factor of 400 and showing scalability well beyond the present demonstration.

Quantum simulations are becoming an essential tool for studying complex phenomena, e.g. quantum topology, quantum information transfer and relativistic wave equations, beyond the limitations of analytical computations and experimental observations. To date, the primary resources used in proof-of-principle experiments are collections of qubits, coherent states or multiple single-particle Fock states. Here we show a quantum simulation performed using genuine higher-order Fock states, with two or more indistinguishable particles occupying the same bosonic mode. This was implemented by interfering pairs of Fock states with up to five photons on an interferometer, and measuring the output states with photon-number-resolving detectors. Already this resource-efficient demonstration reveals topological matter, simulates non-linear systems and elucidates a perfect quantum transfer mechanism which can be used to transport Majorana fermions.

Background:Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the axial skeleton, presenting diagnostic and management challenges. Understanding the epidemiological trends and clinical characteristics of AS is crucial for informed decision-making.Objectives:To analyze the trends and patterns in diagnosis, clinical characteristics, and management of AS over a decade in South Korea, utilizing the National Health Insurance Service (NHIS) database.Methods:This retrospective cohort study utilized data from the Korean NHIS claims database, identifying 31,753 incident AS patients between 2010 and 2021. We calculated age-standardized prevalence and incidence rates, assessed annual incidence trends of AS by age groups, trends in pre-diagnostic sacroiliac (SI) joint magnetic resonance imaging (MRI) utilization, and examined medication usage patterns. We also analyzed the timing of tumor necrosis factor alpha (TNF-α) inhibitor therapy initiation.Results:Over the study period, the age-standardized prevalence rate consistently increased, escalating from 34.6 (95% CI: 34.0 – 35.2) per 100,000 individuals in 2010 to 86.4 (95% CI: 85.6 – 87.3) per 100,000 individuals in 2021. The age-standardized incidence rate also demonstrated year-over-year growth, rising from 4.41 (95% CI: 4.20 – 4.61) per 100,000 person-years in 2010 to 7.63 (95% CI: 7.38 – 7.89) per 100,000 person-years in 2021. The most substantial rise in incidence was observed among younger age groups (Figure 2). Clinical characteristics of patients with incident diagnosis of AS from 2010 to 2021 were evaluated. The mean age at diagnosis was 39.7 ± 15.2, which was higher in females (43.1 ± 15.9 vs. 38.5 ± 14.8 in males, p < 0.001). The male to female ratio was approximately 2.87:1. Uveitis was the most common extra-articular manifestation of AS, occurring in 31.1% of patients, with a higher prevalence in females (33.1% vs. 30.5% in males, p < 0.001). EAMs including uveitis, psoriasis, and ulcerative colitis were more common in female patients (p < 0.05). The percentage of patients who had an SI joint MRI within three months before diagnosis among those newly diagnosed with AS rose from 5.68% in 2011 to 11.9% in 2021 (p for trend < 0.001). Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently prescribed medications (94.8%), while TNF-α inhibitors were used in 31.2% of AS patients. Interleukin-17 inhibitors were approved as second-line biologic therapies after TNF-α inhibitors for reimbursement indication of AS in 2020, and 1.1% of AS patients used them. Notably, 17.4% of newly diagnosed AS patients initiated TNF-α inhibitors within six months after diagnosis, consistently surpassing the rates of those who started treatment between 6 months to 2 years post-diagnosis.Figure 1.Annual age-standardized incidence rate (per 100,000 person-years with 95% CI) and prevalence rate (per 100,000 people with 95% CI) of AS from 2010 to 2021.Figure 2.Annual crude incidence rate (per 100,000 person-years) of AS by age group from 2010 to 2021.Conclusion:This study highlights the growing burden of AS in South Korea, particularly among young individuals. Increasing pre-diagnostic MRI use and early TNF-α inhibitor initiation signify progress in AS diagnosis and management. These findings emphasize the importance of continued research and early intervention to improve patient outcomes and reduce the societal impact of AS.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Growing interest in quantum computing for practical applications has led to a surge in the availability of programmable machines for executing quantum algorithms 1 , 2 . Present-day photonic quantum computers 3 – 7 have been limited either to non-deterministic operation, low photon numbers and rates, or fixed random gate sequences. Here we introduce a full-stack hardware−software system for executing many-photon quantum circuit operations using integrated nanophotonics: a programmable chip, operating at room temperature and interfaced with a fully automated control system. The system enables remote users to execute quantum algorithms that require up to eight modes of strongly squeezed vacuum initialized as two-mode squeezed states in single temporal modes, a fully general and programmable four-mode interferometer, and photon number-resolving readout on all outputs. Detection of multi-photon events with photon numbers and rates exceeding any previous programmable quantum optical demonstration is made possible by strong squeezing and high sampling rates. We verify the non-classicality of the device output, and use the platform to carry out proof-of-principle demonstrations of three quantum algorithms: Gaussian boson sampling, molecular vibronic spectra and graph similarity 8 . These demonstrations validate the platform as a launchpad for scaling photonic technologies for quantum information processing. A system for realizing many-photon quantum circuits is presented, comprising a programmable nanophotonic chip operating at room temperature, interfaced with a fully automated control system.