The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity.

Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy. Mechanistically, LATS1/2-null tumor cells secrete nucleic-acid-rich extracellular vesicles, which induce a type I interferon response via the Toll-like receptors-MYD88/TRIF pathway. LATS1/2 deletion in tumors thus improves tumor immunogenicity, leading to tumor destruction by enhancing anti-tumor immune responses. Our observations uncover a key role of the Hippo pathway in modulating tumor immunogenicity and demonstrate a proof of concept for targeting LATS1/2 in cancer immunotherapy.

CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.

Ultra-compact SOI-based higher-order mode pass wavelength demultiplexer.

We propose an ultra-compact mode filtering wavelength demultiplexer design with a footprint of 3µm×3µm. Our device can route input T E 1 mode signals at 1310 nm and 1550 nm to different output ports while simultaneously blocking fundamental transverse electric (T E 0) mode input. Our device is designed based on the topology optimization algorithm, which results in an ultra-compact footprint combining wavelength routing and mode filtering functions for the first time, to the best of our knowledge. Our final optimized devices demonstrated insertion losses of 1.26 dB and 1.47 dB for the C- and O-band output ports, respectively, with inter-port crosstalk as low as -21.25d B and -30.99d B. The extinction ratios between T E 1 mode and T E 0 mode are 24.02 dB and 30.12 dB at the 1310 nm and 1550 nm output ports. The combination of small footprint, broad transmission bandwidth, T E 1 to T E 0 mode selectively filtering, and C- and O-band T E 1 mode demultiplexing functions make this a uniquely versatile device that can play an important role in future high density mode-wavelength multiplexing systems.

Reducing Re-fractures Post Percutaneous Kyphoplasty: The Impact of Zoledronic Acid with Calcium and Vitamin D3 in Osteoporotic Patients.

Background: Osteoporosis poses a significant health challenge characterized by reduced bone density and increased fracture risk. Percutaneous kyphoplasty, a common treatment, aims to stabilize vertebral fractures. However, adjunctive therapies like zoledronic acid remain underexplored in improving postoperative outcomes and bone health in these patients. Objective: This study aims to evaluate the efficacy of zoledronic acid combined with calcium carbonate and vitamin D3 in treating osteoporosis, providing valuable clinical insights. Methods: A cohort of sixty-six osteoporosis patients who underwent percutaneous kyphoplasty and received subsequent treatment at our hospital between March 2020 and March 2022 were selected. Thirty-three patients received calcium carbonate and vitamin D3 (control group), while the remaining thirty-three patients were treated with zoledronic acid alongside calcium carbonate and vitamin D3 (research group). Pre- and post-treatment assessments included bone mineral density measurements, bone metabolism and turnover marker evaluations, symptom improvement assessments using the Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI), monitoring of adverse reactions, and assessment of quality of life using the Core Quality of Life questionnaire (QOL-C30). A one-year follow-up was conducted to determine re-fracture incidence. Results: Post-treatment, the research group exhibited significantly lower VAS, ODI, tartrate-resistant acid phosphatase-5b, and osteocalcin levels compared to the control group, while bone alkaline phosphatase levels were higher (P < .05). There was no significant difference in adverse reaction incidence between the groups (P > .05), but the research group demonstrated higher QOL-C30 scores (P < .05). Follow-up analysis revealed no notable difference in re-fracture rates between the groups (P > .05). Conclusions: Zoledronic acid in combination with calcium carbonate and vitamin D3 effectively enhances bone health in osteoporosis patients, warranting its clinical recommendation. This regimen shows promise for improving patient outcomes in osteoporosis management.

Missed Nursing Care as a Mediator in the Relationship between Career Calling and Turnover Intention.

AIM: To explore the role of missed nursing care in mediating the relationship between career calling and intention to leave among nurses. INTRODUCTION: Increasing nurse turnover is still a major concern in the global healthcare system. The most reliable indicator of turnover is turnover intention. It is crucial to understand its affecting elements to suggest measures to lower nurses' turnover intention. BACKGROUND: Turnover intention has been linked to career calling and missed nursing care. Little empirical research has investigated the possibility that missed nursing care mediates between career calling and turnover intention. METHODS: A cross-sectional survey of 347 nurses was conducted. The survey instruments included the General Information Questionnaire, Calling Scale, Missed Nursing Care Scale and Turnover Intention Questionnaire. Structural equation models were used to build the model. This study made use of the STROBE checklist. RESULTS: For 43.8% of nurses, turnover intention was high or very high. Missed nursing care and turnover intention were negatively correlated with career calling. Missed nursing care and turnover intention were positively related. Missed nursing care mediated the relationship between career calling and turnover intention. DISCUSSION: Career calling and missed nursing care can both influence turnover intention. Career calling can reduce the likelihood of turnover by preventing missed nursing care. CONCLUSION: Missed nursing care mediated the relationship between career calling and intention to leave. IMPLICATIONS FOR NURSING AND NURSING POLICY: Nursing managers should improve nurses' career calling through professional education and minimize missed nursing care by using electronic nursing reminder devices to reduce turnover intention.

DLGAP5 knockdown inactivates the Wnt/ß-catenin signal to repress endometrial cancer cell malignant activities.

Human discs large-associated protein 5 (DLGAP5), a microtubule-associated protein, has been reported to be upregulated in several tumors. However, the role of DLGAP5 in endometrial cancer (EC) progression and the related underlying mechanism were still unknown. A bioinformatics analysis was performed to analyze the expression and prognostic significance of DLGAP5 in EC tissues using TCGA, CPTAC, Human Protein Atlas, and GSE63678 databases, UALCAN web tool, and the Kaplan-Meier plotter. Effects of DLGAP on EC cell malignant properties were evaluated by CCK-8, flow cytometry analysis, TUNEL assay, caspase-3 activity assay, and Transwell invasion assay. The expression of DLGAP5, Wnt3, c-Myc, Ki67, and cleaved caspase-3 was detected by western blot analysis. DLGAP5 was highly expressed and correlated with poor prognosis in EC patients. DLGAP5 knockdown inhibited proliferation and invasion, triggered apoptosis, and increased caspase-3 activity in EC cells. Additionally, DLGAP5 knockdown inactivated the Wnt/ß-catenin signaling pathway in EC cells. Moreover, ß-catenin overexpression abolished the effects of DLGAP5 knockdown on the malignant phenotypes of EC cells. DLGAP5 silencing suppressed the malignant properties in EC cells by inactivating the Wnt/ß-catenin pathway.

[Follow-up and prognostic study of infants with positional plagiocephaly]. / å©´å„¿ä½“ä½æ€§æ–œå¤´å¼‚å¸¸çš„éšè®¿å’Œé¢„åŽç ”ç©¶.

OBJECTIVES: To study the effects of infantile positional plagiocephaly on the growth and neural development. METHODS: A retrospective study was conducted on the medical data of 467 children who underwent craniographic examination and were followed up to 3 years of age in Peking University Third Hospital from June 2018 to May 2022. They were divided into four groups: mild positional plagiocephaly (n=108), moderate positional plagiocephaly (n=49), severe positional plagiocephaly (n=12), and normal cranial shape (n=298). The general information of the four groups and the weight, length, head circumference, visual acuity screening results, hearing test results, and the scores of Pediatric Neuropsychological Developmental Scales/Gesell Developmental Schedules of the four groups from 6 to 36 months old were compared. RESULTS: The rates of adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping posture in the mild, moderate, and severe positional plagiocephaly groups were higher than the normal cranial group (P<0.05). There was no significant difference in weight, length, and head circumference among the four groups at 6, 12, 24 and 36 months of age (P>0.05). The incidence rate of abnormal vision in the severe positional plagiocephaly group was higher than that in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups at 24 and 36 months of age (P<0.05). The scores of the Pediatric Neuropsychological Developmental Scales at 12 and 24 months of age and the scores of the Gesell Developmental Schedules at 36 months of age in the severe positional plagiocephaly group were lower than those in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups, but the difference was not statistically significant (P>0.05). CONCLUSIONS: Adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping position may be associated with infantile positional plagiocephaly. Mild or moderate positional plagiocephaly has no significant impact on the growth and neural development of children. Severe positional plagiocephaly have adverse effects on the visual acuity. However, it is not considered that severe positional plagiocephaly can affect the neurological development.

DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression.

Evolutionarily conserved DDB1-and CUL4-associated factor 13 (DCAF13) is a recently discovered substrate receptor for the cullin RING-finger ubiquitin ligase 4 (CRL4) E3 ubiquitin ligase that regulates cell cycle progression. DCAF13 is overexpressed in many cancers, although its role in breast cancer is currently elusive. In this study we demonstrate that DCAF13 is overexpressed in human breast cancer and that its overexpression closely correlates with poor prognosis, suggesting that DCAF13 may serve as a diagnostic marker and therapeutic target. We knocked down DCAF13 in breast cancer cell lines using CRISPR/Cas9 and found that DCAF13 deletion markedly reduced breast cancer cell proliferation, clone formation, and migration both in vitro and in vivo. In addition, DCAF13 deletion promoted breast cancer cell apoptosis and senescence, and induced cell cycle arrest in the G1/S phase. Genome-wide RNAseq analysis and western blotting revealed that loss of DCAF13 resulted in both mRNA and protein accumulation of p53 apoptosis effector related to PMP22 (PERP). Knockdown of PERP partially reversed the hampered cell proliferation induced by DCAF13 knockdown. Co-immunoprecipitation assays revealed that DCAF13 and DNA damage-binding protein 1 (DDB1) directly interact with PERP. Overexpression of DDB1 significantly increased PERP polyubiquitination, suggesting that CRL4DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation. In conclusion, DCAF13 and the downstream effector PERP occupy key roles in breast cancer proliferation and potentially serve as prognostics and therapeutic targets.

Jiedutongluotiaogan formula restores pancreatic function by suppressing excessive autophagy and endoplasmic reticulum stress.

CONTEXT: Jiedutongluotiaogan formula (JTTF), a traditional Chinese medicine (TCM), could promote islet function. However, the potential effect of JTTF on endoplasmic reticulum stress (ERS) and autophagy have not been reported. OBJECTIVE: This study explores the potential effect of JTTF on ERS and autophagy in the pancreas. MATERIALS AND METHODS: The Zucker diabetic fatty (ZDF) rats were randomised into five groups, control, model, JTTF (1, 3, 5 g/kg/day for 12 weeks). LPS induced pancreatic ß-cells were treated with JTTF (50, 100, 200 µg/mL). LPS was used to induce pancreatic ß-cell injury, with cell viability and insulin secretion evaluated using MTT, glucose-stimulated insulin secretion (GSIS) assays, and PCR. Intracellular Ca2+ concentration was measured using flow cytometry, while ERS and autophagy levels were monitored via Western blotting and/or immunostaining. RESULTS: Compared with the model group, body weight, FGB, HbA1c, IPGTT, FINs, and HOMA-IR in JTTF treatment groups were significantly reduced. In islets cells treated with JTTF, the pancreatic islet cells in the JTTF group were increased, lipid droplets were reduced, and there was a decrease in Ca2+ (16.67%). After JTTF intervention, PERK, p-PERK, IRE1α, p- IRE1α, ATF6, eIF2α, GRP78, p-ULK1, LC3 and p62 expression decreased, whereas Beclin1and p-mTOR expression increased. In addition, the expression of proteins related to apoptosis in the JTTF groups were lower than those in the control group. DISCUSSION AND CONCLUSIONS: JTTF may alleviate pancreatic ß-cell injury by inhibiting ER stress and excessive autophagy in diabetic rats. This provides a new direction for treating diabetes and restoring pancreatic dysfunction by TCM.

Experimental optimal generation of hybrid entangled states in photonic quantum walks.

While the existence of disorders is commonly believed to weaken the unique properties of quantum systems, recent progress has predicted that it can exhibit a counterintuitive enhanced effect on the behavior of entanglement generation, which is even independent of the chosen initial conditions and physical platforms. However, to achieve a maximally entangled state in such disordered quantum systems, the key limitation of this is the scarcity of an infinite coherence time, which makes its experimental realization challenging. Here, we experimentally investigate the entanglement entropy dynamics in a photonic quantum walk with disorders in time. Through the incorporation of a classic optimization algorithm, we experimentally demonstrate that such disordered systems can relax to a high-entanglement hybrid state at any given time step. Moreover, this prominent entangling ability is universal for a wide variety of initial conditions. Our results may inspire achieving a well-controlled entanglement generator for quantum computation and information tasks.

Prognostic Significance of Microvascular Invasion in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND The incidence, pathogenesis, and prognostic effect of microvascular invasion on pancreatic ductal adenocarcinoma (PDAC) remain controversial. This study aimed to summarize the incidence, pathogenesis, role in clinical management, recurrence, and prognostic significance of microvascular invasion in PDAC. MATERIAL AND METHODS A literature review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Systematic literature searches were conducted using PubMed and Google Scholar up to February 2021. RESULTS Seventeen studies were included in the meta-analysis. The incidence of microvascular invasion was 49.0% (95% confidence interval [CI], 43.8-54.5%) among PDAC patients who underwent surgery. The weighted multivariate Cox proportional hazards model hazard ratio for disease-free survival of 8 studies was 1.78 (95% CI 1.53-2.08, P<0.001), and there was no statistically significant difference between the subgroups (P=0.477). The hazard ratio for overall survival of 14 studies was 1.49 (95% CI 1.27-1.74, P<0.001), and there was no statistically significant difference between the subgroups (P=0.676). CONCLUSIONS Microvascular invasion occurred in nearly half of PDAC patients after surgery and was closely related to disease-free and overall survival. Understanding the role of microvascular invasion in PDAC will help provide more personalized and effective preoperative or postoperative strategies to achieve better survival outcomes.

[Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China].

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (P < 0.05). Compared with the non-MBDP group, the MBDP group had significantly higher incidence rates of neonatal sepsis, anemia, hypocalcemia, and retinopathy of prematurity (P < 0.05). The MBDP group had a significantly lower mean feeding speed, a significantly higher age when reaching total enteral feeding, and a significantly longer duration of parenteral nutrition (P < 0.05). The use rate of caffeine citrate in the MBDP group was significantly higher, but the use rate of erythropoietin was significantly lower than that in the non-MBDP group (P < 0.05). The multivariate logistic regression analysis showed that gestational age < 32 weeks, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis were risk factors for MBDP (P < 0.05). CONCLUSIONS: A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

Period multiplication in mode-locked figure-of-9 fiber lasers.

Period multiplication is a bifurcation phenomenon, which depicts a typical roadmap from periodic steady-state to chaos. There has been particular interest in studying period multiplication properties in mode-locked lasers, but the mechanism behind is still not well-studied. Here, we experimentally demonstrate a figure-of-9 fiber laser which can generate period-multiplied pulses with long-term stability. Further theoretical insight is obtained by numerical simulations, which clearly shows that the ratio between the distances of each bifurcation point is approaching the Feigenbaum constant. We believe that the laser design presented here could be a stable and reliable ultrafast optical platform to study bifurcation and chaos, which also has potential applications in optical frequency comb and all-optical modulation.

Dissipative soliton generation from a large anomalous dispersion ytterbium-doped fiber laser.

Dissipative soliton (DS) is demonstrated in a large anomalous dispersion ytterbium-doped fiber laser. A chirped fiber Bragg grating is implemented into a figure-of-9 cavity to provide a large anomalous dispersion. A self-starting and stable DS operation is achieved with 3.5 nJ pulse energy and 12.9 ps pulse duration under a 26.4 MHz repetition rate. Numerical simulations reveal that the DSs presented here experience strong temporal, spectral, and chirp breathing in the cavity. Thanks to the characteristic chirp breathing, the output DS pulses can maintain a narrow spectral bandwidth of 0.17 nm. We believe that the laser design presented here has a lot of potential and could be an outstanding ultrafast seed laser solution for industrial applications including micromachining and hard-brittle material processing.

Experimental extraction of nonlocal weak values for demonstrating the failure of a product rule.

We experimentally demonstrate an alternative method for measuring nonlocal weak values in linear optics, avoiding the use of second-order interaction. The method is based on the concept of modular values. The paths of two photons, initialized in hyperentangled states, are adopted as the meter with the polarization acting as the system. The modular values are read out through the reconstructed final states of the meter. The weak value of nonlocal observables is given through its connection to the modular value. Comparing the weak values of local and nonlocal observables, we demonstrate the failure of product rules for an entangled system. Our results significantly simplify the task of measuring nonlocal weak values and will play an important role in the application of weak measurement.

Long non-coding RNA OIP5-AS1 suppresses multiple myeloma progression by sponging miR-27a-3p to activate TSC1 expression.

BACKGROUND: Multiple myeloma (MM) is a prevalent hematological malignancy. Long noncoding RNAs are correlated with the development of MM. In this project, the function of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in MM and the potential mechanistic pathway were explored. METHODS: The expression of OIP5-AS1, microRNA (miR)-27a-3p and tuberous sclerosis 1 (TSC1) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Bromodeoxyuridine (BrdU) staining. And cell apoptosis was evaluated by flow cytometry assay. Cell metastasis was assessed utilizing transwell assay. Western blot analysis was employed to detect protein level. The target relation between miR-27a-3p and OIP5-AS1 or TSC1 was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Tumor xenograft assay was conducted to measure the function of OIP5-AS1 in vivo. RESULTS: The expression levels of OIP5-AS1 and TSC1 were decreased in MM, whereas miR-27a-3p was upregulated. High level of OIP5-AS1 could predict favourable prognosis of MM patients. Overexpression of OIP5-AS1 inhibited cell viability, colony formation ability, migration and invasion, induced cell cycle arrest in G1 phase and apoptosis of MM cells in vitro as well as repressed tumorigenesis in vivo. MiR-27a-3p was a target of OIP5-AS1, and reversed the impact of OIP5-AS1 on MM cells. MiR-27a-3p directly targeted TSC1. Silencing of miR-27a-3p repressed MM progression by elevating TSC1 expression. OIP5-AS1 upregulated TSC1 by sponging miR-27a-3p. CONCLUSION: OIP5-AS1 repressed multiple myeloma progression by regulating miR-27a-3p/TSC1 axis.

Raman dissipative soliton fiber laser mode locked by a nonlinear optical loop mirror.

Raman dissipative soliton is generated in a mode locked polarization maintaining fiber laser with a nonlinear optical loop mirror. Ultrafast Raman laser with a repetition rate of 1.23 MHz is obtained. Signal to noise ratio of the radio frequency spectrum of the Raman dissipative soliton is as high as 85 dB. As the pump power increasing, the pulse energy and the spectral width increase, while the pulse width decreases. The highest pulse energy and lowest pulse width is 1.23 nJ and 63 ps, respectively. It is the first report of Raman dissipative soliton generation from an all polarization maintaining mode locked fiber laser to the best of our knowledge. This configuration provides a method to obtain linearly-polarized ultrafast laser at flexible wavelengths.

More than 200 W random Raman fiber laser with ultra-short cavity length based on phosphosilicate fiber.

An over 200 W high-power first-order random Raman fiber laser (RRFL) at 1238 nm is demonstrated. The laser is based on a half-open cavity with a piece of 30 m phosphosilicate fiber. This RRFL is pumped by a conventional 1064 nm Yb-doped fiber laser. After suppressing the silica Raman component, a maximum output power of 206.7 W is obtained with a full width half-maximum linewidth of 7.1 nm at a pump power of 346.3 W, corresponding to an optical-to-optical efficiency of 59.7%. To the best of our knowledge, this is the highest reported output power of RRFL on the basis of phosphosilicate fiber with the shortest cavity length.

Direct Measurement of a Nonlocal Entangled Quantum State.

Entanglement and the wave function description are two of the core concepts that make quantum mechanics such a unique theory. A method to directly measure the wave function, using weak values, was demonstrated by Lundeen et al. [Nature 474, 188 (2011)]. However, it is not applicable to a scenario of two disjoint systems, where nonlocal entanglement can be a crucial element, since that requires obtaining weak values of nonlocal observables. Here, for the first time, we propose a method to directly measure a nonlocal wave function of a bipartite system, using modular values. The method is experimentally implemented for a photon pair in a hyperentangled state, i.e., entangled both in polarization and momentum degrees of freedom.

Measurements of Nonlocal Variables and Demonstration of the Failure of the Product Rule for a Pre- and Postselected Pair of Photons.

We report the first implementation of the von Neumann instantaneous measurements of nonlocal variables, which becomes possible due to technological achievements in creating hyperentangled photons. Tests of reliability and of the nondemolition property of the measurements have been performed with high precision, showing the suitability of the scheme as a basic ingredient of numerous quantum information protocols. The method allows us to demonstrate for the first time with strong measurements a special feature of pre- and postselected quantum systems: the failure of the product rule. It has been verified experimentally that for a particular pre- and postselected pair of particles, a single measurement on particle A yields with certainty σ_{x}^{A}=-1, a single measurement on particle B yields with certainty σ_{y}^{B}=-1, and a single nonlocal measurement on particles A and B yields with certainty σ_{x}^{A}σ_{y}^{B}=-1.