Creation of memory-memory entanglement in a metropolitan quantum network.

Towards realizing the future quantum internet1,2, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research.

CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus.

Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer.

YAP antagonizes TEAD-mediated AR signaling and prostate cancer growth.

Hippo signaling restricts tumor growth by inhibiting the oncogenic potential of YAP/TAZ-TEAD transcriptional complex. Here, we uncover a context-dependent tumor suppressor function of YAP in androgen receptor (AR) positive prostate cancer (PCa) and show that YAP impedes AR+ PCa growth by antagonizing TEAD-mediated AR signaling. TEAD forms a complex with AR to enhance its promoter/enhancer occupancy and transcriptional activity. YAP and AR compete for TEAD binding and consequently, elevated YAP in the nucleus disrupts AR-TEAD interaction and prevents TEAD from promoting AR signaling. Pharmacological inhibition of MST1/2 or LATS1/2, or transgenic activation of YAP suppressed the growth of PCa expressing therapy resistant AR splicing variants. Our study uncovers an unanticipated crosstalk between Hippo and AR signaling pathways, reveals an antagonistic relationship between YAP and TEAD in AR+ PCa, and suggests that targeting the Hippo signaling pathway may provide a therapeutical opportunity to treat PCa driven by therapy resistant AR variants.

Damage-induced regeneration of the intestinal stem cell pool through enteroblast mitosis in the Drosophila midgut.

Many adult tissues and organs including the intestine rely on resident stem cells to maintain homeostasis and regeneration. In mammals, the progenies of intestinal stem cells (ISCs) can dedifferentiate to generate ISCs upon ablation of resident stem cells. However, whether and how mature tissue cells generate ISCs under physiological conditions remains unknown. Here, we show that infection of the Drosophila melanogaster intestine with pathogenic bacteria induces entry of enteroblasts (EBs), which are ISC progenies, into the mitotic cycle through upregulation of epidermal growth factor receptor (EGFR)-Ras signaling. We also show that ectopic activation of EGFR-Ras signaling in EBs is sufficient to drive enteroblast mitosis cell autonomously. Furthermore, we find that the dividing enteroblasts do not gain ISC identity as a prerequisite to divide, and the regenerative ISCs are produced through EB mitosis. Taken together, our work uncovers a new role for EGFR-Ras signaling in driving EB mitosis and replenishing the ISC pool during fly intestinal regeneration, which may have important implications for tissue homeostasis and tumorigenesis in vertebrates.

Fluctuotaxis: Nanoscale directional motion away from regions of fluctuation.

Regulating the motion of nanoscale objects on a solid surface is vital for a broad range of technologies such as nanotechnology, biotechnology, and mechanotechnology. In spite of impressive advances achieved in the field, there is still a lack of a robust mechanism which can operate under a wide range of situations and in a controllable manner. Here, we report a mechanism capable of controllably driving directed motion of any nanoobjects (e.g., nanoparticles, biomolecules, etc.) in both solid and liquid forms. We show via molecular dynamics simulations that a nanoobject would move preferentially away from the fluctuating region of an underlying substrate, a phenomenon termed fluctuotaxis-for which the driving force originates from the difference in atomic fluctuations of the substrate behind and ahead of the object. In particular, we find that the driving force can depend quadratically on both the amplitude and frequency of the substrate and can thus be tuned flexibly. The proposed driving mechanism provides a robust and controllable way for nanoscale mass delivery and has potential in various applications including nanomotors, molecular machines, etc.

Fluid shear stress-mediated Piezo1 alleviates osteocyte apoptosis by activating the PI3K/Akt pathway.

Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 h, FSS at 9 dyne/cm2 for 30 min, Yoda1 treatment for 2 h, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 min significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.

New Insights into the Role of Humic Acid in Permanganate Oxidation of Diclofenac: A Novel Electron Transfer Mechanism.

Humic acid (HA) ubiquitously existing in aquatic environments has been reported to significantly impact permanganate (KMnO4) decontamination processes. However, the underlying mechanism of the KMnO4/HA system remained elusive. In this study, an enhancing effect of HA on the KMnO4 oxidation of diclofenac (DCF) was observed over a wide solution pH range of 5-9. Surprisingly, the mechanism of HA-induced enhancement varied with solution pH. Quenching and chemical probing experiments revealed that manganese intermediates (Mn(III)-HA and MnO2) were responsible for the enhancement under acidic conditions but not under neutral and alkaline conditions. By combining KMnO4 decomposition, galvanic oxidation process experiments, electrochemical tests, and FTIR and XPS analysis, it was interestingly found that HA could effectively mediate the electron transfer from DCF to KMnO4 in neutral and alkaline solutions, which was reported for the first time. The formation of an organic-catalyst complex (i.e., HA-DCF) with lower reduction potential than the parent DCF was proposed to be responsible for the accelerated electron transfer from DCF to KMnO4. This electron transfer likely occurred within the complex molecule formed through the interaction between HA-DCF and KMnO4 (i.e., HA-DCF-KMnO4). These results will help us gain a more comprehensive understanding of the role of HA in the KMnO4 oxidation processes.

Symmetry constraints on the orientation dependence of high-order elastic constants for the hexagonal boron nitride monolayer.

Group theory is a powerful tool to explore fundamental symmetry constraints for the physical properties of crystal structures, e.g. it is well-known that only a few components of the elastic constants are independent due to the symmetry constraint. This work further applies group theory to derive constraint relationships for high-order elastic constants with respect to the orientation angle, where the constraint relationships are more explicit than the traditional tensor transformation law. These analytic symmetry constraints are adopted to explain the molecular dynamics simulation results, which disclose that the high-order elastic constants are highly anisotropic with an anisotropy percentage of up to 25% for the hexagonal boron nitride monolayer. The elastic constant is a basic quantity in the mechanics field, so its high anisotropy shall cause strong anisotropy for other mechanical properties. Based on the anisotropic high-order elastic constants, we demonstrate that Poisson's ratio is highly anisotropic for the hexagonal boron nitride at large strains. These findings provide fundamental insights into the symmetry dependence of high-order elastic constants and other mechanical properties.

Flexible nanomechanical bit based on few-layer graphene.

Mechanical computers have gained intense research interest at size scales ranging from nano to macro as they may complement electronic computers operating in extreme environments. While nanoscale mechanical computers may be easier to integrate with traditional electronic components, most current nanomechanical computers are based on volatile resonator systems that require continuous energy input. In this study, we propose a non-volatile nanomechanical bit based on the quasi-stable configurations of few-layer graphene with void defects, and demonstrate its multiple quasi-stable states by deriving an analytic relationship for the void configuration based on a competition between the bending energy and the cohesive energy. Using this nanomechanical bit, typical logic gates are constructed to perform Boolean calculations, including NOT, AND, OR, NAND and NOR gates, and demonstrate reprogrammability between these logic gates. We also study the accuracy and the stability of the nanomechanical bits based on the few-layer graphene. These findings provide a novel approach to realize the nanomechanical computing process.

Artificial Intelligence Aids Detection of Rotator Cuff Pathology: A Systematic Review.

PURPOSE: To determine the model performance of artificial intelligence (AI) in detecting rotator cuff pathology using different imaging modalities and to compare capability with physicians in clinical scenarios. METHODS: The review followed the PRISMA guidelines and was registered on PROSPERO. The criteria were as follows: 1) studies on the application of AI in detecting rotator cuff pathology using medical images, and 2) studies on smart devices for assisting in diagnosis were excluded. The following data were extracted and recorded: statistical characteristics, input features, AI algorithms used, sample sizes of training and testing sets, and model performance. The data extracted from the included studies were narratively reviewed. RESULTS: A total of 14 articles, comprising 23,119 patients, met the inclusion and exclusion criteria. The pooled mean age of the patients was 56.7 years, and the female rate was 56.1%. The area under the curve (AUC) of the algorithmic model to detect rotator cuff pathology from ultrasound images, MRI images, and radiographic series ranged from 0.789 to 0.950, 0.844 to 0.943, and 0.820 to 0.830, respectively. Notably, 1 of the studies reported that AI models based on ultrasound images demonstrated a diagnostic performance similar to that of radiologists. Another comparative study demonstrated that AI models using MRI images exhibited greater accuracy and specificity compared to orthopedic surgeons in the diagnosis of rotator cuff pathology, albeit not in sensitivity. CONCLUSIONS: The detection of rotator cuff pathology has been significantly aided by the exceptional performance of AI models. In particular, these models are equally adept as musculoskeletal radiologists in using ultrasound to diagnose rotator cuff pathology. Furthermore, AI models exhibit statistically superior levels of accuracy and specificity when using MRI to diagnose rotator cuff pathology, albeit with no marked difference in sensitivity, in comparison to orthopaedic surgeons. LEVEL OF EVIDENCE: Level III, systematic review of Level III studies.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

Effect of Salicylic Acid Treatment on Disease Resistance to Coleosporium zanthoxyli in Chinese Pepper (Zanthoxylum armatum).

The fungus Coleosporium zanthoxyli causes leaf rust in Chinese pepper (Zanthoxylum armatum). To investigate the control effect of elicitor treatment on leaf rust in this species, the impact of salicylic acid (SA) on the spores and growth of C. zanthoxyli and the induced resistance to leaf rust by Z. armatum were analyzed, and the possible defense mechanisms involved in SA induction were evaluated. The results showed that SA had no effect on C. zanthoxyli spore germination and growth; however, rust resistance was induced in Z. armatum. The optimal SA treatment concentration was 0.4 mg/ml, and the relative cure effect reached 44.56%. SA-induced disease resistance was evident for up to 10 days, while the optimal induction interval was 48 h after stimulation. Consistent with the induced resistance, H2O2, total protein, total phenol, and lignin concentrations and polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia lyase (PAL), superoxide dismutase (SOD), and catalase (CAT) activities were significantly increased with the SA treatment, whereas the malondialdehyde content was significantly decreased. In addition, exogenous SA promoted defense-related enzyme activities, including those of POD, CAT, and PAL, and increased H2O2, lignin, and endogenous SA contents. Furthermore, SA induced the expression of SA signaling pathway genes such as ZaPR1 and ZaNPR1, and silencing ZaPR1 enhanced the sensitivity of Z. armatum to leaf rust. Our results demonstrated that 0.4 mg/ml SA priming increased the activities of CAT, POD, and PAL, elevated the contents of H2O2, lignin, and endogenous SA, and upregulated the expression of the SA-related gene ZaPR1, thereby enhancing the resistance of Z. armatum to leaf rust.

Comparison of self-efficacy among graduate teaching assistants before and after training.

BACKGROUND: Teaching assistants (TAs) play a crucial role in pedagogical practices, and the TA training has emerged as a vital strategy for enhancing teaching quality and fostering effective interactions. The self-efficacy of TAs can substantially impact their performance. Nevertheless, little research has focused on the change in TAs' self-efficacy following their training. METHODS: A self-control quasi-experiment was conducted to examine shifts in the self-efficacy of Tas at Peking University before and after their TA training. A questionnaire was used to assess the change, and the reliability and validity of the questionnaire was also calculated. A paired data rank sum test was used to analysis the changes in TA self-efficacy before and after training. RESULTS: A total of 372 TAs from School of Basic Medicine (N = 173), School of Pharmacy (N = 112), School of Public Health (N = 69), and other schools (N = 18) submitted complete questionnaires. The questionnaire showed a good performance in internal reliability and validity test (Cronbach's alpha index = 0.906, and KMO value was 0.903). Participants had a median total self-efficacy score of 88 and 85 before and after the TA training, respectively, which shows a lack in the total TA self-efficacy score following the TA training (P < 0.001). TAs who have no desire to becoming a college instructor have a higher self-efficacy when compared to TAs who have expressed neutral attitudes in becoming college instructors. CONCLUSION: The participated TAs display a lack of self-efficacy after attending the TA training at Peking University. Therefore, it is necessary to establish and strengthen TA's self-efficacy beyond academic skills when designing and delivering TA training programs at Peking University.

The Empathy for Pain Stimuli System (EPSS): Development and preliminary validation.

We present the Empathy for Pain Stimuli System (EPSS): a large-scale database of stimuli for studying people's empathy for pain. The EPSS comprises five sub-databases. First, the Empathy for Limb Pain Picture Database (EPSS-Limb) provides 68 painful and 68 non-painful limb pictures, exhibiting people's limbs in painful and non-painful situations, respectively. Second, the Empathy for Face Pain Picture Database (EPSS-Face) provides 80 painful and 80 non-painful pictures of people's faces being penetrated by a syringe or touched by a Q-tip. Third, the Empathy for Voice Pain Database (EPSS-Voice) provides 30 painful and 30 non-painful voices exhibiting either short vocal cries of pain or neutral interjections. Fourth, the Empathy for Action Pain Video Database (EPSS-Action_Video) provides 239 painful and 239 non-painful videos of whole-body actions. Finally, the Empathy for Action Pain Picture Database (EPSS-Action_Picture) provides 239 painful and 239 non-painful pictures of whole-body actions. To validate the stimuli in the EPSS, participants evaluated the stimuli using four different scales, rating pain intensity, affective valence, arousal, and dominance. The EPSS is available to download for free at https://osf.io/muyah/?view_only=33ecf6c574cc4e2bbbaee775b299c6c1 .

Hedgehog signaling mechanism and role in cancer.

Cell-cell communication through evolutionarily conserved signaling pathways governs embryonic development and adult tissue homeostasis. Deregulation of these signaling pathways has been implicated in a wide range of human diseases including cancer. One such pathway is the Hedgehog (Hh) pathway, which was originally discovered in Drosophila and later found to play a fundamental role in human development and diseases. Abnormal Hh pathway activation is a major driver of basal cell carcinomas (BCC) and medulloblastoma. Hh exerts it biological influence through a largely conserved signal transduction pathway from the activation of the GPCR family transmembrane protein Smoothened (Smo) to the conversion of latent Zn-finger transcription factors Gli/Ci proteins from their repressor (GliR/CiR) to activator (GliA/CiA) forms. Studies from model organisms and human patients have provided deep insight into the Hh signal transduction mechanisms, revealed roles of Hh signaling in a wide range of human cancers, and suggested multiple strategies for targeting this pathway in cancer treatment.

Babesia microti Causing Intravascular Hemolysis in Immunocompetent Child, China.

We report a case of Babesia microti infection in an immunocompetent child <5 years of age that caused fever and severe intravascular hemolysis. Physicians in China should be aware of babesiosis, especially in the differential diagnosis of immune hemolytic anemia with negative results for antiglobulin tests.

Effect and mechanisms of dexmedetomidine combined with macrophage migration inhibitory factor inhibition on the expression of inflammatory factors and AMPK in mice.

Reperfusion after acute myocardial infarction can cause ischemia/reperfusion (I/R) injury, which not only impedes restoration of the functions of tissues and organs but may also aggravate structural tissue and organ damage and dysfunction, worsening the patient's condition. Thus, the mechanisms that underpin myocardial I/R injury need to be better understood. We aimed to examine the effect of dexmedetomidine on macrophage migration inhibitory factor (MIF) in cardiomyocytes from mice with myocardial I/R injury and to explore the mechanistic role of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling in this process. Myocardial I/R injury was induced in mice. The expression of serum inflammatory factors, reactive oxygen species (ROS), adenosine triphosphate (ATP), and AMPK pathway-related proteins, as well as myocardial tissue structure and cell apoptosis rate, were compared between mice with I/R injury only; mice with I/R injury treated with dexmedetomidine, ISO-1 (MIF inhibitor), or both; and sham-operated mice. Dexmedetomidine reduced serum interleukin (IL)-6 and tumor necrosis factor-α concentrations and increased IL-10 concentration in mice with I/R injury. Moreover, dexmedetomidine reduced myocardial tissue ROS content and apoptosis rate and increased ATP content and MIF expression. MIF inhibition using ISO-1 reversed the protective effect of dexmedetomidine on myocardial I/R injury and reduced AMPK phosphorylation. Dexmedetomidine reduces the inflammatory response in mice with I/R injury and improves adverse symptoms, and its mechanism of action may be related to the MIF-AMPK pathway.

A functional near-infrared spectroscopy study on hemodynamic changes of patients with prolonged disorders of consciousness responding to different auditory stimuli.

Treating prolonged disorders of consciousness (pDoC) is challenging. Thus, accurate assessment of residual consciousness in patients with pDoC is important for the management and recovery of patients. Functional near-infrared spectroscopy (fNIRS) can be used to detect brain activity through changes of oxygenated hemoglobin/deoxygenated hemoglobin (HbO/HbR) concentrations changes and has recently gained increasing attention for its potential applications in assessing residual consciousness. However, the number of fNIRS studies assessing residual awareness in patients with pDoC is still limited. In this study, fNIRS was used to evaluate the brain function in 18 patients with pDoC, including 14 vegetative states (VS) and 4 minimally conscious states (MCS), and 15 healthy controls (HC). All participants accepted two types of external stimuli, i.e., active stimulation (motor imagery, MI) and passive stimulation (subject's own name, SON). The results showed that the mean concentrations of HbO/HbR in the prefrontal cortex of the HC during the passive stimulation were significantly lower than those of the active stimulation, and the fitting slope was high. However, the hemodynamic responses of the patients with pDoC were opposite to those of the HC. Additionally, the mean concentrations of HbO/HbR increased as the level of consciousness decreased during passive stimulation. Our findings suggest that the residual level of consciousness in pDoC patients can be assessed by measuring brain responses to different stimulations using fNIRS. The present study further demonstrates the feasibility and reliability of fNIRS in assessing residual consciousness in patients with pDoC, providing a basis for its expanded clinical application.

Visible-light-induced halocyclization of 2-alkynylthioanisoles with simple alkyl halides towards 3-halobenzo[b]thiophenes without an external photocatalyst.

A new strategy for the preparation of 3-halobenzo[b]thiophenes via a photo-driven halocyclization/demethylation of 2-alkynylthioanisoles with simple alkyl halides was developed. The reaction can proceed smoothly at room temperature under visible-light irradiation without any external photocatalyst, and the protocol has a range of advantages, including simplicity and mildness of the reaction conditions, good functional-group tolerance, and excellent yields of the products.

Machine learning accelerated search for the impact limit of the graphene/aluminum alloy whipple structure.

This paper proposes a Whipple structure to enhance the impact resistance of graphene/aluminum alloy composites by varying the interlayer spacing between graphene and aluminum alloy. The increased interlayer spacing provides more deformation space for the graphene to absorb more deformation energy, and enables the formation of a debris cloud from the bullet fragments and graphene fragments, significantly reducing the impact energy per unit area of the next material. The impact limit serves as a critical metric for assessing the impact resistance of the Whipple structure. Based on molecular dynamics simulations, we developed a machine learning model to predict the protection of aluminum alloy, and quickly determined the impact limits of velocity, bullet radius, and interlayer spacing by using the machine learning model. An empirical equation for the impact limit of interlayer spacing was established. The results showed that non-zero interlayer spacing can significantly improve the impact resistance of the hybrid structure; to fully exploit the superior impact resistance of this Whipple structure, the number of graphene layers should be at least 3. Furthermore, at high impact velocities and large bullet radii, the impact limit of the interlayer spacing exhibits a substantial correlation with the number of graphene layers. These results provide valuable information for the design of the impact resistance of the graphene/aluminum alloy composites.