Certification of Genuine Multipartite Entanglement with General and Robust Device-Independent Witnesses.

Genuine multipartite entanglement represents the strongest type of entanglement, which is an essential resource for quantum information processing. Standard methods to detect genuine multipartite entanglement, e.g., entanglement witnesses, state tomography, or quantum state verification, require full knowledge of the Hilbert space dimension and precise calibration of measurement devices, which are usually difficult to acquire in an experiment. The most radical way to overcome these problems is to detect entanglement solely based on the Bell-like correlations of measurement outcomes collected in the experiment, namely, device independently. However, it is difficult to certify genuine entanglement of practical multipartite states in this way, and even more difficult to quantify it, due to the difficulty in identifying optimal multipartite Bell inequalities and protocols tolerant to state impurity. In this Letter, we explore a general and robust device-independent method that can be applied to various realistic multipartite quantum states in arbitrary finite dimension, while merely relying on bipartite Bell inequalities. Our method allows us both to certify the presence of genuine multipartite entanglement and to quantify it. Several important classes of entangled states are tested with this method, leading to the detection of genuinely entangled states. We also certify genuine multipartite entanglement in weakly entangled Greenberger-Horne-Zeilinger states, showing that the method applies equally well to less standard states.

Improving the precision of optical metrology by detecting fewer photons with biased weak measurement.

In optical metrological protocols to measure physical quantities, it is, in principle, always beneficial to increase photon number n to improve measurement precision. However, practical constraints prevent the arbitrary increase of n due to the imperfections of a practical detector, especially when the detector response is dominated by the saturation effect. In this work, we show that a modified weak measurement protocol, namely, biased weak measurement significantly improves the precision of optical metrology in the presence of saturation effect. This method detects an ultra-small fraction of photons while maintains a considerable amount of metrological information. The biased pre-coupling leads to an additional reduction of photons in the post-selection and generates an extinction point in the spectrum distribution, which is extremely sensitive to the estimated parameter and difficult to be saturated. Therefore, the Fisher information can be persistently enhanced by increasing the photon number. In our magnetic-sensing experiment, biased weak measurement achieves precision approximately one order of magnitude better than those of previously used methods. The proposed method can be applied in various optical measurement schemes to remarkably mitigate the detector saturation effect with low-cost apparatuses.

Beating Standard Quantum Limit with Weak Measurement.

Weak measurements have been under intensive investigation in both experiment and theory. Numerous experiments have indicated that the amplified meter shift is produced by the post-selection, yielding an improved precision compared to conventional methods. However, this amplification effect comes at the cost of a reduced rate of acquiring data, which leads to an increasing uncertainty to determine the level of meter shift. From this point of view, a number of theoretical works have suggested that weak measurements cannot improve the precision, or even damage the metrology information due to the post-selection. In this review, we give a comprehensive analysis of the weak measurements to justify their positive effect on prompting measurement precision. As a further step, we introduce two modified weak measurement protocols to boost the precision beyond the standard quantum limit. Compared to previous works beating the standard quantum limit, these protocols are free of using entangled or squeezed states. The achieved precision outperforms that of the conventional method by two orders of magnitude and attains a practical Heisenberg scaling up to n=106 photons.

Extracting information from single qubits among multiple observers with optimal weak measurements.

In the context of quantum information, major efforts have been made to maximize the mutual information by measuring single copies of signal states. In general, one execution of optimal projective measurement extracts all the accessible mutual information. However, in some scenarios, weak measurements are preferred because of kinds of specific requirements, e.g., to distribute secret keys to multi-observers. In this study, we propose a method to construct optimal weak measurements for multi-party quantum communications. Utilizing the method in [Physical Review Letters 120, 160501 (2018)] to classify the mutual information, the theoretical study shows that by successively performing this optimal weak measurement, all accessible information can be obtained by multiple observers. This conclusion is experimentally verified by a cascaded measurement apparatus that can perform six successive weak measurements on heralded single photons. The experimental results clearly indicate that almost all accessible mutual information is extracted by this sequence of optimal weak measurements; meanwhile, none of the information is destroyed or residual. Thus, this optimal weak measurement is an efficient and reliable tool for performing quantum communication tasks. The consistence between the experimental and theoretical results verifies that the classifying method in [Phys. Rev. Lett.120, 160501 (2018)] can be applied to characterize realistic quantum measurements.

Homoharringtonine acts synergistically with SG235-TRAIL, a conditionally replicating adenovirus, in human leukemia cell lines.

AIM: To investigate the synergistic effects of SG235-TRAIL, a novel oncolytic adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and homoharringtonine (HHT) in human leukemia cell lines. METHODS: The combined effect of SG235-TRAIL and HHT was assessed using a crystal violet assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, followed by combination index analysis. Cell apoptosis was measured using flow cytometry combined with fluorescein-isothiocyanate-Annexin V staining. The activation of caspase pathway and the expression of Bcl-2 family proteins, TRAIL, and E1A were examined using Western blotting. RESULTS: HHT synergized the cytotoxicity of SG235-TRAIL against leukemia cell lines Kasumi-1, KG-1, HL-60, and U937, concomitantly with increased apoptosis and enhanced activity of caspase-3 and -9. The combination therapy resulted in significantly lower levels of Bcl-2, Mcl-1, and Bid compared to treatment of cells with either HHT or SG235-TRAIL alone, suggesting that HHT sensitizes leukemia cells to SG235-TRAIL virus through alteration of anti-apoptotic signaling elements. Importantly, HHT combined with SG235-TRAIL did not show significant cytotoxicity to normal human mononuclear cells and mesenchymal stem cells. CONCLUSION: Combining oncolytic adenovirus SG235-TRAIL and HHT synergistically enhances cytotoxicity in leukemia cells in vitro, suggesting that the combination therapy could represent a rational approach for the treatment of leukemia.

Suppression of cancer growth in mice by adeno-associated virus vector-mediated IFN-beta expression driven by hTERT promoter.

Adeno-associated virus (AAV) has rapidly become a promising gene delivery vehicle for its excellent advantages of non-immunogenic, low pathogenicity and long-term gene expression in vivo. However, a major obstacle in development of effective AAV vector is the lack of tissue specificity, which caused low efficiency of AAV transfer to target cells. The application of human telomerase reverse transcriptase (hTERT) promoter is a prior targeting strategy for AAV in cancer gene therapy as hTERT activity is transcriptionally upregulated in most cancer cells. In the present work, we investigated whether AAV-mediated human interferon beta (IFN-beta) gene driven by hTERT promoter could specifically express in tumor cells and suppress tumor cell growth. Our data demonstrated that hTERT promoter-driven IFN-beta expression was the tumor-specific, decreased the cell viability of tumor cells but not normal cells, and induced tumor cell apoptosis via activation of caspase pathway and release of cytochrome c. AAV-mediated IFN-beta expression driven by hTERT promoter significantly suppressed the growth of colorectal cancer and lung cancer xenograft in mice and resulted in tumor cells death in vivo. These data suggested that AAVs in combination with hTERT-mediated IFN-beta expression could exert potential antitumor activity and provide a novel targeting approach to clinical gene therapy of varieties of cancers.

Mannose-exposing myeloid leukemia cells detected by the sCAR-PPA fusion protein.

Altered glycosylation may be a hallmark of malignant transformation and cancer progression. In the work described, a specific mannose-binding lectin, Pinellia pedatisecta agglutinin (PPA), was genetically fused with the extracellular domain of coxsackie-adenovirus receptor (CAR) to generate the soluble CAR (sCAR)-PPA fusion protein. The adenoviral transduction of acute myeloid leukemia (AML) cell lines Kasumi-1 and HL-60 was increased by sCAR-PPA, indicating that a fraction of AML cells exposing mannose residues was detected by PPA. However, sCAR-PPA did not increase the adenoviral infection of KG-1 cells, suggesting the mannose exposure of AML cells may be cell type specific. Furthermore, the infectious efficiency of Ad-EGFP in chronic myeloid leukemia cell line K562 was significantly increased by sCAR-PPA as well. We, herein, report that PPA recognized a fraction of myeloid leukemia cells showing mannose-exposing phenotype. The sCAR-PPA fusion protein combined with the adenoviral vector system may provide a useful tool for investigating myeloid leukemia cells exposing mannose residues and further elucidating the role of these cells in the leukemia development.

Potent antitumor effect of interleukin-24 gene in the survivin promoter and retinoblastoma double-regulated oncolytic adenovirus.

Interleukin (IL)-24 is an excellent therapeutic gene for cancer therapy. In this work, IL-24 was inserted into Ad.sp-E1A(Delta24), an oncolytic adenovirus with a 24-bp deletion in the E1A gene, which was driven by the survivin promoter to form Ad.sp-E1A(Delta24)-IL-24. Ad.sp-E1A(Delta24)-IL-24 has an excellent antitumor effect in vitro for human nasopharyngeal, liver, lung, and cervical carcinoma cell lines but does no or little damage to normal cell lines L-02 and WI38. Furthermore, it achieved nearly complete inhibition (although not elimination) of NCI-H460 lung carcinoma growth in nude mice. The antitumor efficacy of Ad.sp-E1A(Delta24)-IL-24 on NCI-H460 cells was clearly mediated by apoptosis, because it induced caspase-3 and poly(ADP-ribose) polymerase cleavage. This is the first report of Ad.sp-E1A(Delta24)-IL-24 with such an excellent, broad, and specific antitumor effect in vitro and nearly complete inhibition of lung tumor growth in vivo.

Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24.

AIM: The aim of this study was to creatively implement a novel chemo-gene-virotherapeutic strategy and further strengthen the antitumor effect in cancer cells by the combined use of ZD55-IL-24 and cisplatin. METHODS: ZD55-IL-24 is an oncolytic adenovirus that harbors interleukin 24 (IL-24), which has a strong antitumor effect and was identified and evaluated by PCR, RT-PCR, and Western blot analysis. Enhancement of cancer cell death using a combination of ZD55-IL-24 and cisplatin was assessed in several cancer cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cytopathic effect (CPE) assay. Apoptosis induction by treatment with ZD55-IL-24 and/or cisplatin was detected in BEL7404 and SMMC7721 by morphological evaluation, apoptotic cell staining, and flow cytometry analysis. In addition, negative effects on normal cells were evaluated in the L-02 cell line using the MTT assay, the CPE assay, morphological evaluation, apoptotic cell staining, and flow cytometry analysis. RESULTS: The combination of ZD55-IL-24 and cisplatin, which is superior to ZD55-IL-24, cisplatin, and ZD55-EGFP, as well as ZD55-EGFP plus cisplatin, resulted in a significantly increased effect. Most importantly, conjugation of ZD55-IL-24 with cisplatin had toxic effects equal to that of cisplatin and did not have overlapping toxicities in normal cells. CONCLUSION: This study showed that ZD55-IL-24 conjugated with cisplatin exhibited a remarkably increased cytotoxic and apoptosis-inducing effect in cancer cells and significantly reduced the toxicity in normal cells through the use of a reduced dose.