Multimode heralded single photons based on the DLCZ.

High-quality single-photon sources are crucial for the development of simple quantum devices. Quantum communication stands at the forefront of cutting-edge technologies, promising unprecedented levels of security and efficiency. A cornerstone of this revolutionary field is the development of high-speed single-photon sources, which play a pivotal role in quantum key distribution and other quantum communication protocols. In this context, the concept of space multimode emerges as a promising avenue to propel the capabilities of single-photon sources to new heights. We have spatial multiplexing technology to develop single-photon sources that deliver high-speed heralded single photons in the Duan-Lukin-Cirac-Zoller (DLCZ) scheme. We propose a spatial multiplexing single-photon source scheme based on the DLCZ. Compared to a single spatial mode, by adding six spatial modes through spatial multiplexing, the single-photon generation rate increases 4.3 times. And the second-order correlation function of single photons is less than 0.5. We show that expanding the spatial degrees of freedom of the quantum storage scheme based on DLCZ does not affect the single-photon properties. The generation rate of the single photon can be significantly increased through spatial multiplexing with a feedback circuit. Our approach offers a promising path to creating a high-speed photon source based on a spatial multimode scheme.

Effect of mesencephalic astrocyte-derived neurotrophic factor on the inflammatory response in human gingival fibroblasts cells.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a unique member of the neurotrophic factor family residing in the endoplasmic reticulum, where it functions as a stress response protein maintaining endoplasmic reticulum homeostasis, in addition to being secreted extracellularly as a neurotrophic factor to bind with receptors to initiate intracellular signal transduction pathways. Interestingly, MANF has shown an important protective role in the inflammatory response of many diseases. In neural stem cells, pancreatic ß cells, and retinal cells, MANF can inhibit the inflammatory response, modulate the immune response, and promote tissue repair. However, the role of MANF in the periodontal inflammatory response remains unclear. In the present study, we used lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) to establish a Pg-LPS-stimulated periodontal inflammatory model in human gingival fibroblasts cells (HGF-1) to investigate the role of MANF in vitro. We found that MANF could inhibit pro-inflammatory cytokine secretion, alleviate the endoplasmic reticulum stress response, promote cell survival, and inhibit cell apoptosis. Therefore, MANF might be a novel promising target for the treatment of periodontitis.

TIVC: An Efficient Local Search Algorithm for Minimum Vertex Cover in Large Graphs.

The minimum vertex cover (MVC) problem is a canonical NP-hard combinatorial optimization problem aiming to find the smallest set of vertices such that every edge has at least one endpoint in the set. This problem has extensive applications in cybersecurity, scheduling, and monitoring link failures in wireless sensor networks (WSNs). Numerous local search algorithms have been proposed to obtain "good" vertex coverage. However, due to the NP-hard nature, it is challenging to efficiently solve the MVC problem, especially on large graphs. In this paper, we propose an efficient local search algorithm for MVC called TIVC, which is based on two main ideas: a 3-improvements (TI) framework with a tiny perturbation and edge selection strategy. We conducted experiments on real-world large instances of a massive graph benchmark. Compared with three state-of-the-art MVC algorithms, TIVC shows superior performance in accuracy and possesses a remarkable ability to identify significantly smaller vertex covers on many graphs.

Generation of entanglement between a highly wave-packet-tunable photon and a spin-wave memory in cold atoms.

Controls of waveforms (pulse durations) of single photons are important tasks for effectively interconnecting disparate atomic memories in hybrid quantum networks. So far, the waveform control of a single photon that is entangled with an atomic memory remains unexplored. Here, we demonstrated control of waveform length of the photon that is entangled with an atomic spin-wave memory by varying light-atom interaction time in cold atoms. The Bell parameter S as a function of the duration of photon pulse is measured, which shows that violations of Bell inequality can be achieved for the photon pulse in the duration range from 40 ns to 50 µs, where, S = 2.64 ± 0.02 and S = 2.26 ± 0.05 for the 40-ns and 50-µs durations, respectively. The measured results show that S parameter decreases with the increase in the pulse duration. We confirm that the increase in photon noise probability per pulse with the pulse-duration is responsible for the S decrease.

Variations of tongue coating microbiota in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: Variations in the oral microbiota have been significantly correlated with the progress of autoimmune diseases, such as immunoglobulin A nephropathy and Henoch-Schönlein purpura (HSP). However, there is no report outlining the character of tongue coating microbiota variations in children with Henoch-Schönlein purpura nephritis (HSPN). METHOD: A total of 20 children with HSPN and 14 healthy controls were recruited for this research. Tongue coating samples of two groups were collected for 16S rRNA gene sequencing. The diversity, principal component analysis (PCA), nonmetric multidimensional scaling (NMDS), partial least squares discriminant analysis (PLS-DA), and linear discriminant analysis (LDA) effect size (LEfSe) were performed. Microbial function was assessed using the PICRUST. RESULTS: The ACE and Chao indices were greatly lower in the HSPN group than in the HG (P = 0.001). The Shannon and Simpson indices were dramatically reduced in children with HSPN compared with those in the healthy controls (P = 0.005). Bacteroidales, Selenomonadales, Lactobacillales, Fusobacteriales, Neisseriales, and Actinomycetales composed more than 80% of all sequences, while Bacteroidales was the most generous order in both groups. PCA, NMDS and PLS-DA showed a marked difference between the control and HSPN groups. LEfSe analysis showed alteration of tongue coating microbiota in the HSPN group. There were 30 metabolic functions significantly differed between the two groups. CONCLUSIONS: Children with HSPN have substantially various tongue coating microbiota compared to healthy controls. Even though this research does not indicate causality, it is beneficial to enhance the possibility for coming microbial-based treatments to enhance the clinical effects of HSPN in children.

Telitacicept as a BLyS/APRIL dual inhibitor for autoimmune disease.

The pathogenic roles for B cells in autoimmunity include produce pathogenic autoantibodies and modulate immune responses via the production of cytokines and chemokines. The B lymphocyte stimulator BLyS (also known as B-cell-activating factor, BAFF) and APRIL (a proliferation-inducing ligand) are critical factors in the maintenance of the B-cell pool and humoral immunity, namely BLyS modulates the differentiation and maturation of immature B cell, while APRIL modulates the function and survival of long-lived plasma cell, which plays a prominent role in the pathogenesis of autoimmune diseases. Telitacicept is a novel recombinant fusion protein of both the ligand-binding domain of the TACI receptor and the Fc component of human IgG and which is a BLyS/APRIL dual inhibitor. Moreover, telitacicept was developed by Remegen Co., Ltd. in China and is approved to treat systemic lupus erythematosus in China. We review the rationale, clinical evidence, and future perspectives of telitacicept for the treatment of autoimmune disease.HighlightThe B lymphocyte stimulator BLyS (also known as B-cell-activating factor, BAFF) and APRIL (a proliferation-inducing ligand), members of tumor necrosis factor (TNF) family, and which are critical factors in the maintenance of the B-cell pool and humoral immunity.BAFF and APRIL are implicated in the pathogenesis of several human autoimmune diseases with autoreactive B-cell involvement, and targeting both is beneficial for the treatment of autoimmune diseases.Telitacicept is a novel recombinant fusion protein of both the ligand-binding domain of the TACI receptor and the Fc component of human IgG, as a BLyS/APRIL dual inhibitor and which has been approved by National Medical Products Administration (MNPA) for the treatment of patients with SLE in China.With more clinical trials underway, telitacicept may also be approved for the treatment of other autoimmune diseases in the future.

Research on a Task Offloading Strategy for the Internet of Vehicles Based on Reinforcement Learning.

Today, vehicles are increasingly being connected to the Internet of Things, which enables them to obtain high-quality services. However, the numerous vehicular applications and time-varying network status make it challenging for onboard terminals to achieve efficient computing. Therefore, based on a three-stage model of local-edge clouds and reinforcement learning, we propose a task offloading algorithm for the Internet of Vehicles (IoV). First, we establish communication methods between vehicles and their cost functions. In addition, according to the real-time state of vehicles, we analyze their computing requirements and the price function. Finally, we propose an experience-driven offloading strategy based on multi-agent reinforcement learning. The simulation results show that the algorithm increases the probability of success for the task and achieves a balance between the task vehicle delay, expenditure, task vehicle utility and service vehicle utility under various constraints.

KIF18B promotes hepatocellular carcinoma progression through activating Wnt/ß-catenin-signaling pathway.

This study aimed to investigate the functional roles of kinesin family member 18B (KIF18B) in hepatocellular carcinoma (HCC) development, as well as the related molecular mechanisms. Tissue specimens were collected from 105 patients with HCC, and the messenger RNA (mRNA) and protein levels of KIF18B were detected using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The χ2 test was performed to estimate the association of KIF18B with clinical characteristics of patients with HCC. Effects of KIF18B expression on biological behaviors of HCC cells were detected by clone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and transwell assays. The expression patterns of proteins were investigated using Western blot analysis. HCC tissues and cell lines showed significant upregulation of KIF18B at both mRNA and protein levels (p > .05, for all). Furthermore, the elevated KIF18B expression was positively correlated with the tumor-node-metastasis stage (p = .015) and lymph node metastasis (p = .007). Knockdown of KIF18B might suppress HCC cell clone formation, proliferation, migration, and invasion in vitro. Besides, the activity of Wnt/ß-catenin pathway was also significantly inhibited after the KIF18B knockdown. However, the antitumor actions caused by KIF18B knockdown might be reversed by lithium chloride treatment, which was the inducer of Wnt/ß-catenin-signaling pathway. KIF18B may serve as an oncogene in HCC through enhancing the activity of Wnt/ß-catenin pathway.

Cavity-enhanced and long-lived optical memories for two orthogonal polarizations in cold atoms.

The storage and retrieval efficiency (SRE) and lifetime of optical quantum memories are two key performance indicators for scaling up quantum information processing. Here, we experimentally demonstrate a cavity-enhanced long-lived optical memory for two polarizations in a cold atomic ensemble. Using electromagnetically induced-transparency (EIT) dynamics, we demonstrate the storages of left-circularly and right-circularly polarized signal light pulses in the atoms, respectively. By making the signal and control beams collinearly pass through the atoms and storing the two polarizations of the signal light as two magnetic-field-insensitive spin waves, we achieve a long-lived (3.5 ms) memory. By placing a low-finesse optical ring cavity around the cold atoms, the coupling between the signal light and the atoms is enhanced, which leads to an increase in SRE. The presented cavity-enhanced storage shows that the SRE is ∼30%, corresponding to an intrinsic SRE of ∼45%.

Deterministic generation and partial retrieval of a spin-wave excitation in an atomic ensemble.

In this paper, we report a generation of a spin-wave excitation (SWE) with a near-unity (0.996±0.003) probability in a given time (~730 µ s). Such deterministic generation relies on a feedback scheme with a millisecond quantum memory. The millisecond memory is achieved by maximizing the wavelength of the spin wave and storing the SWE as the magnetic-field-insensitive transition. We then demonstrate partial retrievals of the spin wave by applying a first read pulse whose area is smaller than the value of π. The remained SWE is fully retrieved by a second pulse. Anti-correlation function between the detections in the first and second readouts has been measured, which shows that the partial-retrieval operation on the SWE is in the quantum regime. The presented experiment represents an important step towards the realization of the improved DLCZ quantum repeater protocol proposed in Phys. Rev. A 77, 062301 (2008).

Sparse Labeling and Neural Tracing in Brain Circuits by STARS Strategy: Revealing Morphological Development of Type II Spiral Ganglion Neurons.

Elucidating axonal and dendritic projection patterns of individual neurons is a key for understanding the cytoarchitecture of neural circuits in the brain. This requires genetic approaches to achieve Golgi-like sparse labeling of desired types of neurons. Here, we explored a novel strategy of stochastic gene activation with regulated sparseness (STARS), in which the stochastic choice between 2 competing Cre-lox recombination events is controlled by varying the lox efficiency and cassette length. In a created STARS transgenic mouse crossed with various Cre driver lines, sparse neuronal labeling with a relatively uniform level of sparseness was achieved across different brain regions and cell types in both central and peripheral nervous systems. Tracing of individual type II peripheral auditory fibers revealed for the first time that they undergo experience-dependent developmental refinement, which is impaired by attenuating external sound input. Our results suggest that STARS strategy can be applied for circuit mapping and sparse gene manipulation.

Spatial Multiplexing of Atom-Photon Entanglement Sources using Feedforward Control and Switching Networks.

The light-matter quantum interface that can create quantum correlations or entanglement between a photon and one atomic collective excitation is a fundamental building block for a quantum repeater. The intrinsic limit is that the probability of preparing such nonclassical atom-photon correlations has to be kept low in order to suppress multiexcitation. To enhance this probability without introducing multiexcitation errors, a promising scheme is to apply multimode memories to the interface. Significant progress has been made in temporal, spectral, and spatial multiplexing memories, but the enhanced probability for generating the entangled atom-photon pair has not been experimentally realized. Here, by using six spin-wave-photon entanglement sources, a switching network, and feedforward control, we build a multiplexed light-matter interface and then demonstrate a ∼sixfold (∼fourfold) probability increase in generating entangled atom-photon (photon-photon) pairs. The measured compositive Bell parameter for the multiplexed interface is 2.49±0.03 combined with a memory lifetime of up to ∼51 µs.

The active intrathecal B-cell response in LGI1-antibody encephalitis.

BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) is a component of the voltage-gated potassium channel complex. IgG antibodies against LGI1 are associated with immunotherapy-responsive encephalitis and epilepsies. LGI1-antibody concentrations are 10-100 times greater in serum than in cerebrospinal fluid (CSF). Oligoclonal IgG bands are rarely found in patients with LGI1-antibody encephalitis or epilepsy. These observations raise questions about the sources of the B cells that result in production of LGI1 antibodies and how the IgGs reach the brain. We aimed to investigate the migration and expansions of peripheral and central B cells to the production of LGI1-specific IgG. METHODS: We performed PCR amplification and next generation deep immune repertoire sequencing of immunoglobulin (Ig) heavy chain variable regions (VH) from CSF and subsorted peripheral blood B-cell populations from two patients with limbic encephalitis and faciobrachial dystonic seizures associated with LGI1 antibodies. Bioinformatics clustering of related IgM-VH or IgG-VH transcripts was used to determine whether active B-cell diversification could be observed, and whether intrathecal B-cell repertoires, if present, were related to peripheral B cells. FINDINGS: We identified clusters of related Ig-VH transcripts in the CSF of both patients. Within these clusters there was a range of somatic hypermutations along the IGHV germline segment-derived portion. In addition, we identified a large number of closely related Ig-VH clusters that were common to both CSF and peripheral blood, including a small number of dominating Ig-VH clusters that might represent the most active clonally related B-cell populations. INTERPRETATION: Our data suggest that some B-cell affinity maturation occurs inside the CNS compartment in LGI1-antibody encephalitis. Somatic hypermutation rates point to a CSF antigen-driven activation of clonally related B cells that shape the intrathecal immune repertoire. The target antigen or antigens of these clonally related B cells remain unknown; our work continues to determine the relative contribution of intrathecally activated and peripheral LGI1-specific B cells in this autoimmune CNS disease. FUNDING: Wellcome Trust Intermediate Fellowship to SRI, Fulbright-MS Society, Epilepsy Research UK, BMA Vera Down Research Grant.

Slit/Robo signaling mediates spatial positioning of spiral ganglion neurons during development of cochlear innervation.

During the development of periphery auditory circuits, spiral ganglion neurons (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with their soma aggregated into a cluster spatially segregated from the cochlear sensory epithelium. The molecular mechanisms underlying this spatial patterning remain unclear. In this study, in situ hybridization in the mouse cochlea suggests that Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression patterns in the spiral ganglion and its nearby region, the spiral limbus. In Slit2 and Robo1/2 mutants, the spatial restriction of SGNs was disrupted. Mispositioned SGNs were found to scatter in the space between the cochlear epithelium and the main body of spiral ganglion, and the neurites of mispositioned SGNs were misrouted and failed to innervate HCs. Furthermore, in Robo1/2 mutants, SGNs were displaced toward the cochlear epithelium as an entirety. Examination of different embryonic stages in the mutants revealed that the mispositioning of SGNs was due to a progressive displacement to ectopic locations after their initial normal settlement at an earlier stage. Our results suggest that Slit/Robo signaling imposes a restriction force on SGNs to ensure their precise positioning for correct SGN-HC innervations.

Doppler perfusion index and contrast-enhanced ultrasound in patients with colorectal cancer liver metastases.

BACKGROUND/AIMS: To assess the value of the Doppler perfusion index (DPI) and contrast agent for the detection of liver metastases in patients with colorectal cancer. METHODOLOGY: DPI was measured in 18 patients with colorectal cancer liver metastases and 18 control subjects. Sixteen patients were underwent contrast-enhanced ultrasonography (CEUS). RESULTS: patients with liver metastases had significantly greater DPI than control group (0.39 +/- 0.10 vs. 0.19 +/- 0.07, p < 0.05). Sixteen liver metastasis lesions underwent a rapid wash-out of contrast agent during the portal venous phase followed by a complete wash-out of SonoVue during the sinusoidal phase and were differentiated as "fast-in and fast-out" contrast enhancement patter. Another 3 lesions which were not found by baseline ultrasonography were detected to be enhancement defects at sinusoidal phases by CEUS. CONCLUSIONS: DPI is a sensitive index in detection of colorectal liver metastases; if used combined with contrast agent, much more occult liver metastasis would be detected by ultrasonography.

From behavior to bio-inspiration: Aerial reorientation and multi-plane stability in kangaroo rats, computational models, and robots.

Tails play essential roles in functions related to locomotor stability and maneuverability among terrestrial and arboreal animals. In kangaroo rats, bipedal hopping rodents, tails are used as effective inertial appendages for stability in hopping, but also facilitate stability and maneuverability during predator escape leaps. The complexity of tail functionality shows great potential for bio-inspiration and robotic device design, as maneuvering is accomplished by a long and light-weight inertial appendage. To (i) further understand the mechanics of how kangaroo rats use their tails during aerial maneuvers, and to (ii) explore if we can achieve this behavior with a simplified tail-like appendage (i.e., template), we combined quantified animal observations, computational simulations, and experiments with a two degrees of freedom (2-DoF) tailed robot. We used video data from free-ranging kangaroo rats escaping from a simulated predator and analyzed body and tail motion for the airborne phase. To explain tail contributions to body orientation (i.e., spatial reorientation), we built a mid-air kangaroo rat computational model and demonstrate that three-dimensional body orientation of the model can be controlled by a simplified 2-DoF tail with a nonlinear control strategy. Resulting simulated trajectories show movement patterns similar to those observed in kangaroo rats. Our robot experiments show that a lightweight tail can generate a large yaw displacement and stabilize pitch and roll angles to zero, simultaneously. Our work contributes to better understanding of the form-function relationship of the kangaroo rat tail and lays out an important foundation for bio-inspiration in robotic devices that have lightweight tail-like appendages for mid-air maneuvering.

Broadening of inhibitory tuning underlies contrast-dependent sharpening of orientation selectivity in mouse visual cortex.

Orientation selectivity (OS) in the visual cortex has been found to be invariant to increases in stimulus contrast, a finding that cannot be accounted for by the original, purely excitatory Hubel and Wiesel model. This property of OS may be important for preserving the quality of perceived stimulus across a range of stimulus intensity. The synaptic mechanisms that can prevent a broadening of OS caused by contrast-dependent strengthening of excitatory inputs to cortical neurons remain unknown. Using in vivo loose-patch recordings, we found in excitatory neurons in layer 4 of mouse primary visual cortex (V1) that the spike response to the preferred orientation was elevated as contrast increased while that to the orthogonal orientation remained unchanged, resulting in an overall sharpening rather than a weakening of OS. Whole-cell voltage-clamp recordings further revealed that contrast increases resulted in a scaling up of excitatory conductance at all stimulus orientations. Inhibitory conductance was enhanced at a similar level as excitation for the preferred orientation, but at a significantly higher level for the orthogonal orientation. Modeling revealed that the resulting broadening of inhibitory tuning is critical for maintaining and sharpening OS at high contrast. Finally, two-photon imaging guided recordings from parvalbumin-positive (PV) inhibitory neurons revealed that the broadening of inhibition can be attributed to a contrast-dependent broadening of spike-response tuning of PV neurons. Together our results suggest that modulation of synaptic inhibition in the mouse V1 cortical circuit preserves the sharpness of response selectivity during changes of stimulus strength.

Functional elimination of excitatory feedforward inputs underlies developmental refinement of visual receptive fields in zebrafish.

In many sensory systems, receptive fields (RFs) measured by spike responses undergo progressive refinement during development. It has been proposed that elimination of excitatory synaptic inputs underlies such functional refinement. However, despite many extracellular recording and anatomical studies, direct in vivo intracellular evidence has remained limited. In this study, by cell-attached recordings in the developing optic tectum of zebrafish, we found that during a short period after the initial formation of retinotectal synapses, spike visual RFs of tectal neurons underwent a two-stage developmental modulation: from an initial expansion to a later refinement. Whole-cell voltage-clamp recordings revealed that the underlying excitatory synaptic RF exhibited a similar developmental progression, with its spatial extent first increased and then reduced, and its spatial tuning profile gradually sharpened. The inhibitory RF was initially larger than the excitatory RF but became matched with the excitatory RF at later stages. Simulation with the integrate-and-fire neuron model suggested that the developmental changes of excitatory RFs primarily accounted for the initial enlargement and later refinement of spike RFs, whereas inhibitory inputs generally reduced the size of the spike RF without affecting its developmental progression. In addition, spike RF of individual retinal ganglion cells did not significantly change in size during the same period, and the spatial extent and tuning profile of the tectal excitatory RF barely changed after intratectal excitatory connections were silenced. Together, our results demonstrate that the functional refinement of tectal visual RFs results primarily from a selective elimination of feedforward retinotectal inputs.

Immunohistochemical evidence of the prognostic value of hedgehog pathway components in primary gallbladder carcinoma.

PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis. RESULTS: Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. Expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC. CONCLUSIONS: To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC.