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Abstract Objective The aim of this study was to investigate the relationship between circulating levels of B cell activating factor (BAFF) and the presence and severity of coronary artery disease (CAD) and acute myocardial infarction (AMI) in humans, as its biological functions in this context remain unclear. Methods Serum BAFF levels were measured in a cohort of 723 patients undergoing angiography, including 204 patients without CAD (control group), 220 patients with stable CAD (CAD group), and 299 patients with AMI (AMI group). Logistic regression analyses were used to assess the association between BAFF and CAD or AMI. Results Significantly elevated levels of BAFF were observed in patients with CAD and AMI compared to the control group. Furthermore, BAFF levels exhibited a positive correlation with the SYNTAX score (r = 0.3002, P

Abstract Kitaev interactions, arising from the interplay of frustration and bond anisotropy, can lead to strong quantum fluctuations and, in an ideal case, to a quantum-spin-liquid state. However, in many nonideal materials, spurious non-Kitaev interactions typically promote a zigzag antiferromagnetic order in the d-orbital transition-metal compounds. Here, by combining neutron scattering with muon-spin rotation and relaxation techniques, we provide mechanism insights into the exotic properties of Na2Co2TeO6, a candidate material of the Kitaev model. Below T N, the zero-field muon-spin relaxation rate becomes almost constant (~0.45 μs−1). We attribute this temperature-independent relaxation rate to the strong quantum fluctuations, as well as to the frustrated Kitaev interactions. As the magnetic field increases, neutron scattering data indicate a broader spin-wave excitation at the K-point. Therefore, quantum fluctuations seem not only robust but are even enhanced by the applied magnetic field. Our findings provide valuable hints for understanding the onset of the quantum-spin-liquid state in Kitaev materials.

Abstract Background Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. Objectives This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. Materials and methods Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. Results Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. Conclusions Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Summary: Lissencephaly is a rare brain malformation for which our understanding remains limited due to the absence of suitable animal models that accurately represent human phenotypes. Here, we establish doublecortin (DCX) knockout ferrets as a model that faithfully replicates key features of the disorder. We reveal the critical roles of DCX in neural progenitor cell proliferation and radial glial fiber extension, processes essential for normal cortical development. Utilizing single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics, we provide a detailed atlas of the lissencephalic cortex, illustrating disrupted neuronal lamination and the specific interactions between inhibitory and excitatory neurons. These findings enhance our understanding of the cellular and molecular mechanisms underlying lissencephaly and highlight the potential of DCX knockout ferrets as a valuable tool for neurodevelopmental research, offering insights into both the pathology of lissencephaly and the general principles of brain development.

Abstract Human cerebellar development is orchestrated by molecular regulatory networks to achieve cytoarchitecture and coordinate motor and cognitive functions. Here, we combined single-cell transcriptomics, spatial transcriptomics and single cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development. We revealed that combinations of transcription factors and cis-regulatory elements (CREs) play roles in governing progenitor differentiation and cell fate determination along trajectories in a hierarchical manner, providing a gene expression regulatory map of cell fate and spatial information for these cells. We also illustrated that granule cells located in different regions of the cerebellar cortex showed distinct molecular signatures regulated by different signals during development. Finally, we mapped single-nucleotide polymorphisms (SNPs) of disorders related to cerebellar dysfunction and discovered that several disorder-associated genes showed spatiotemporal and cell type-specific expression patterns only in humans, indicating the cellular basis and possible mechanisms of the pathogenesis of neuropsychiatric disorders.

Abstract Flat bands are rare in pristine solids and are unstable against electronic correlations or other types of long-range order. Unlike atomic-scale Hubbard systems or Moiré materials, where electronic correlations are either localized or long-ranged, pristine flat band systems with short-range interactions that do not break symmetry spontaneously are less known and intriguing. These systems could bridge the gap between atomic Mott insulators and Moiré correlated insulators, offering a unique platform to explore their mysterious relation. Using an analytical analysis, further verified by numerical calculations, we show that monolayer Nb3Cl8 is a unique flat band system with short-range interactions. We present clear evidence that it is a cluster Mott insulator, which nicely explains the electronic structure observed in angle-resolved photoemission spectroscopy. We further propose that monolayer Nb3Cl8 may constitute a rare example of molecular quantum spin liquid with flat bands.

Abstract Consciousness arises from the spatiotemporal neural dynamics, however, its relationship with neural flexibility and regional specialization remains elusive. We identified a consciousness-related signature marked by shifting spontaneous fluctuations along a unimodal-transmodal cortical axis. This simple signature is sensitive to altered states of consciousness in single individuals, exhibiting abnormal elevation under psychedelics and in psychosis. The hierarchical dynamic reflects brain state changes in global integration and connectome diversity under task-free conditions. Quasi-periodic pattern detection revealed that hierarchical heterogeneity as spatiotemporally propagating waves linking to arousal. A similar pattern can be observed in macaque electrocorticography. Furthermore, the spatial distribution of principal cortical gradient preferentially recapitulated the genetic transcription levels of the histaminergic system and that of the functional connectome mapping of the tuberomammillary nucleus, which promotes wakefulness. Combining behavioral, neuroimaging, electrophysiological, and transcriptomic evidence, we propose that global consciousness is supported by efficient hierarchical processing constrained along a low-dimensional macroscale gradient.

Abstract The amygdala, or an amygdala-like structure, is found in the brains of all vertebrates and plays a critical role in survival and reproduction. However, the cellular architecture of the amygdala and how it has evolved remain elusive. Here, we generated single-nucleus RNA-sequencing data for more than 200,000 cells in the amygdala of humans, macaques, mice, and chickens. Abundant neuronal cell types from different amygdala subnuclei were identified in all datasets. Cross-species analysis revealed that inhibitory neurons and inhibitory neuron-enriched subnuclei of the amygdala were well-conserved in cellular composition and marker gene expression, whereas excitatory neuron-enriched subnuclei were relatively divergent. Furthermore, LAMP5 + interneurons were much more abundant in primates, while DRD2 + inhibitory neurons and LAMP5 + SATB2 + excitatory neurons were dominant in the human central amygdalar nucleus (CEA) and basolateral amygdalar complex (BLA), respectively. We also identified CEA-like neurons and their species-specific distribution patterns in chickens. This study highlights the extreme cell-type diversity in the amygdala and reveals the conservation and divergence of cell types and gene expression patterns across species that may contribute to species-specific adaptations.

With the acceleration of the global warming process, the clean energy crisis is becoming serious; conventional energy is unlikely to solve the current crisis, so people pay attention to new energy. As wave energy is widely distributed, renewable, and clean, hundreds of wave energy converters emerge. In order to understand the research progress of wave energy converters better, this paper divides wave energy converters into overtopping type, oscillating water column type, and oscillating body type according to the working principle and divides the oscillating body type into oscillating float type and oscillating pendulum type by different ways of energy capture. Based on the classification, various types of engineering cases, physical tests and digital simulation, and other academic research results are summarized, especially the generation power and energy conversion efficiency of various devices, and some shortcomings and suggestions are put forward, hoping to provide help for readers to study wave energy generation converters.

This study analyzes the ambient vibrations induced while running the Mount Changlong pumped-storage power station (PSPS). The ground vibration data of the power station during its operation were acquired with vibration sensors. Different units were selected and compared under working conditions, and the conclusions were as follows: (1) Ambient vibrations induced by the running of units constituted the primary source of vibration, and they attenuated as the distance increased. (2) The vibration acceleration under pumping conditions was larger than that under power generation conditions, and the ground vibration acceleration increased with an augmentation of the power. (3) The running of adjacent units generated mutual interference, and the types of units were different, which led to complex variations in the spectrum maps. (4) The vibration acceleration of the lower flat tunnel was prone to surpassing the standard when the number of units running together exceeded three.

Grasping the concerns of customers is paramount, serving as a foundation for both attracting and retaining a loyal customer base. While customer satisfaction has been extensively explored across diverse industries, there remains a dearth of insights into how distinct rural bed and breakfasts (RB&Bs) can effectively cater to the specific needs of their target audience. This research utilized latent semantic analysis and text regression techniques on online reviews, uncovering previously unrecognized factors contributing to RB&B customer satisfaction. Furthermore, the study demonstrates that certain factors wield distinct impacts on guest satisfaction within varying RB&B market segments. The implications of these findings extend to empowering RB&B owners with actionable insights to enhance the overall customer experience.

Lung cancer is one of the leading causes of cancer-related deaths worldwide. However, there are currently limited treatment options that are widely available to patients with advanced lung cancer, and further research is required to inhibit or reverse disease progression more effectively. In lung and other solid tumor cancers, autophagy and glycometabolic reprograming are critical regulators of malignant development, including proliferation, drug resistance, invasion, and metastasis. To provide a theoretical basis for therapeutic strategies targeting autophagy and glycometabolic reprograming to prevent lung cancer, we review how autophagy and glycometabolism are regulated in the malignant development of lung cancer based on research progress in other solid tumors.

Experimental tests on two tandem triangular prisms were accomplished in synergistic flow-induced motion (FIM) to collect ocean current energy (OCE) with varied spacing ratios and Reynolds number ranges. Typical FIM responses and energy conversion are discussed and presented. The effects of parameters (system stiffness, spacing ratio, and load resistance) were considered to improve the energy harvesting of the system. The main findings can be summarized as follows: 1) with varied spacing ratios between the two tandem prisms, the active power (Pharn) was up to 1.95 times that of the single triangular prism (STP); 2) In general, the harnessed OCE capacity of the upstream triangular prism (UTP) was improved, while the energy harvesting of the downstream triangular prism (DTP) was suppressed by the interaction of the two prisms, 3) In the tests, electricity was generated at U = 0.516 m/s, and the active power, which consistently increased as flow velocity increased, reached Pharn = 32.24 W, with a corresponding efficiency of ηharn = 10.31%; and 4) The best energy conservation performance for harvesting the OCE occurred at L/D = 5, and the optimal load resistance was found at RL = 11 Ω.

IntroductionGastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown.MethodsThe keywords “neutrophil extracellular traps and gastric cancer” were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p

Abstract We study many-body localization (MBL) in a spin-chain model mimicking the Rydberg-blockade quantum simulator with infinite-strength projection and moderate quasiperiodic modulation. Employing exact diagonalization, Krylov-typicality technique, and time-evolving block decimation, we identify evidence for a constrained MBL phase stabilized by a pure quasirandom transverse field. Intriguingly, the constrained MBL transition may embody a discontinuous eigenstate phase transition, whose discontinuity nature significantly suppresses finite-size drifts that plague most numerical studies of conventional MBL transition. Through quantum dynamics, we find that rotating the modulated field from parallel toward perpendicular to the projection axis induces an eigenstate transition between diagonal and constrained MBL phases. The entanglement-entropy growth in constrained MBL follows a double-log form, whereas it changes to a power law in approaching the diagonal limit. By unveiling confined nonlocal effects in integrals of motion of constrained MBL, we show this insulating state is not a many-body Anderson insulator. Our predictions are testable in Rydberg experiments.

Abstract Background The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. Objectives This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). Material and methods Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. Results Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P

The evolution of epigenetic regulation of brain development in primates is not well understood. Here, the authors perform a comparative study of epigenetic dynamics of early prefrontal cortex development between human and rhesus macaque, finding divergent regulatory elements that may be related to cognitive capacity.

Background: Gastric cancer (GC) is one of the most common malignancies in the human digestive tract. CD4+T cells can eliminate tumor cells directly through the mechanism of cytolysis, they can also indirectly attack tumor cells by regulating the tumor TME. A prognostic model of CD4+T cells is urgently needed to improve treatment strategies and explore the specifics of this interaction between CD4+T cells and gastric cancer cells. Methods: The detailed data of GC samples were downloaded from the Cancer Genome Atlas (TCGA), GSE66229, and GSE84437 datasets. CD4+ T cell-related genes were identified to construct a risk-score model by using the Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset. In addition, postoperative pathological tissues of 139 gastric cancer patients were randomly selected for immunohistochemical staining, and their prognostic information were collected for external verification. Immune and molecular characteristics of these samples and their predictive efficacy in immunotherapy and chemotherapy were analysed.Results: The training set and validation set had consistent results, with GC patients of high PROC and SERPINE1 expression having poorer prognosis. In order to improve their clinical application value, we constructed a risk scoring model and established a high-precision nomogram. Low-risk patients had a better overall survival (OS) than high-risk patients, consistent with the results from the GEO cohort. Furthermore, the risk-score model can predict infiltration of immune cells in the tumor microenvironment of GC, as well as the response of immunotherapy. Correlations between the abundance of immune cells with PROC and SERPINE1 genes were shown in the prognostic model according to the training cohort. Finally, sensitive drugs were identified for patients in different risk subgroup.Conclusion: The risk model not only provides a basis for better prognosis in GC patients, but also is a potential prognostic indicator to distinguish the molecular and immune characteristics of the tumor, and its response to immune checkpoint inhibitor (ICI) therapy and chemotherapy.

T-type calcium channels are implicated in many diseases. Here, multiple structures of CaV3.3 channel elucidate molecular mechanisms of T-type CaV channels activation at low voltage and interaction with different clinically used channel blockers.

Detected scattered photons can cause cupping and streak artifacts, significantly degrading the quality of CT images. For fast and accurate estimation of scatter intensities resulting from photon interactions with a phantom, we first transform the path probability of photons interacting with the phantom into a high-dimensional integral. Secondly, we develope a new efficient algorithm called gQMCFFD, which combines graphics processing unit(GPU)-based quasi-Monte Carlo (QMC) with forced fixed detection to approximate this integral. QMC uses low discrepancy sequences for simulation and is deterministic versions of Monte Carlo. Numerical experiments show that the results are in excellent agreement and the efficiency improvement factors are 4 ∼ 46 times in all simulations by gQMCFFD with comparison to GPU-based Monte Carlo methods. And by combining gQMCFFD with sparse matrix method, the simulation time is reduced to 2 seconds in a single projection angle and the relative difference is 3.53%.

The intratumoural heterogeneity of spinal ependymomas and the role of microglia in tumour progression remain underexplored. Here, the authors perform single-cell RNA- and ATAC-sequencing data analysis of three subtypes and reveal tumour-associated macrophage subsets with distinct functional phenotypes.

The honeycomb lattice with a spin-orbit interaction can give rise to exotic quantum states. With the measurements of bulk properties and inelastic neutron scattering, Lin et al demonstrate the existence of a field induced spin-disordered state in Na2Co2TeO6 and extend the Kitaev model to 3d system.

Abstract A family of spin–orbit coupled honeycomb Mott insulators offers a playground to search for quantum spin liquids (QSLs) via bond-dependent interactions. In candidate materials, a symmetric off-diagonal Γ term, close cousin of Kitaev interaction, has emerged as another source of frustration that is essential for complete understanding of these systems. However, the ground state of honeycomb Γ model remains elusive, with a suggested zigzag magnetic order. Here we attempt to resolve the puzzle by perturbing the Γ region with a staggered Heisenberg interaction which favours the zigzag ordering. Despite such favour, we find a wide disordered region inclusive of the Γ limit in the phase diagram. Further, this phase exhibits a vanishing energy gap, a collapse of excitation spectrum, and a logarithmic entanglement entropy scaling on long cylinders, indicating a gapless QSL. Other quantities such as plaquette-plaquette correlation are also discussed.

Abstract In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced cell reprogramming offers a temporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram astrocytes into neurons. The in situ chemically induced neurons resemble endogenous neurons in terms of neuron-specific marker expression, electrophysiological properties, and synaptic connectivity. Our study demonstrates the feasibility of in vivo chemical reprogramming in the adult mouse brain and provides a potential approach for developing neuronal replacement therapies.

Objectives: The B cell activating factor (BAFF) is a B cell survival factor involved in atherosclerosis and ischemia-reperfusion (IR) injury. This study sought to investigate whether BAFF is a potential predictor of poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Methods: We prospectively enrolled 299 patients with STEMI, and serum levels of BAFF were measured. All subjects were followed for three years. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal reinfarction, hospitalization for heart failure (HF), and stroke. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of BAFF for MACEs. Results: In multivariate analysis, BAFF was independently associated with risk of MACEs (adjusted HR 1.525, 95% CI 1.085–2.145; p = 0.015) and cardiovascular death (adjusted hazard ratio [HR] 3.632, 95% confidence interval [CI] 1.132–11.650, p = 0.030) after adjustment for traditional risk factors. Kaplan-Meier survival curves demonstrated that patients with BAFF levels above the cut-off value (1.46 ng/mL) were more likely to have MACEs (log-rank p < 0.0001) and cardiovascular death (log-rank p < 0.0001). In subgroup analysis, the impact of high BAFF on MACEs development was stronger in patients without dyslipidemia. Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with BAFF as an independent risk factor or when combined with cardiac troponin I. Conclusions: This study suggests that higher BAFF levels in the acute phase are an independent predictor of the incidence of MACEs in patients with STEMI.

The ability to control magnetic coupling in graphene nanomaterials remains elusive. Here, the authors report an approach of engineering magnetic ground states in open-shell bipartite/nonbipartite nanographenes where the magnetic coupling sign between two spins are controlled via breaking bipartite lattice symmetry.

The hypothalamus performs a wide range of vital physiological functions, including growth and reproductive behaviors, and circadian rhythms. The authors identify and characterize hypothalamic radial glial and hypothalamic mantle zone radial glial cells as the neural progenitors in the hypothalamus.

Abstract Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome profiles of single light-stimulated neuron in V1 remain unknown. In our study, in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as light-sensitive (LS) or non-light-sensitive (NS) by single-cell light-evoked calcium evaluation and action potential spiking. The contents of each cell after functional tests were aspirated in vivo through a patch-clamp pipette for mRNA sequencing. Moreover, the three-dimensional (3-D) morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings. Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation, such as Rtn4r and Rgs7, and genes involved in membrane transport, such as Na+/K+ ATPase and NMDA-type glutamatergic receptors, preferentially responded to light stimulation. Furthermore, an antagonist that blocks Rtn4r signals could inactivate the neuronal responses to light stimulation in live mice. In conclusion, our findings of the vivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.

Summary: Recent studies have demonstrated that human astrocytes and fibroblasts can be directly converted into functional neurons by small molecules. However, fibroblasts, as a potentially better cell resource for transplantation, are not as easy to reprogram as astrocytes regarding their fate to neurons, and chemically induced neurons (iNs) with low efficiency from fibroblasts resulted in limited application for the treatment of neurological disorders, including depression. Here, we report that human fibroblasts can be efficiently and directly reprogrammed into glutamatergic neuron-like cells by serially exposing cells to a combination of small molecules. These iNs displayed neuronal transcriptional networks, and also exhibited mature firing patterns and formed functional synapses. Importantly, iNs could integrate into local circuits after transplantation into postnatal mouse brain. Our study provides a rapid and efficient transgene-free approach for chemically generating neuron-like cells from human fibroblasts. Furthermore, our approach offers strategies for disease modeling and drug discovery in central nervous system disorders. : In this article, Dai and colleagues show that human fibroblasts can be efficiently and directly reprogrammed into glutamatergic neuron-like cells by a combination of small molecules. These iNs displayed neuronal transcriptional networks, exhibited mature firing patterns and could also integrate into local circuits after transplantation. The study provides an efficient transgene-free approach for chemically generating neuron-like cells from human fibroblasts. Keywords: direct reprogramming, fibroblasts to neurons, small molecules, high efficiency, cell transplantation, glutamatergic neurons

A series of experimental tests on flow-induced motion (FIM) and energy conversion of two rigidly coupled triangular prisms (TRCTP) in tandem arrangement were conducted in a recirculating water channel with the constant oscillation mass mosc. The incoming flow velocity covered the range of 0.395 m/s ≤ U ≤ 1.438 m/s, corresponding to the Reynolds number range of 3.45 × 104 ≤ Re ≤ 1.25 × 105. The upstream and downstream triangular prisms with a width of 0.1 m and length of 0.9 m were connected by two rectangular endplates. Seven stiffness (1000 N/m ≤ K ≤ 2400 N/m), five load resistances (8 Ω ≤ RL ≤ 23 Ω), and five gap ratios (1 ≤ L/D ≤ 4) were selected as the parameters, and the FIM responses and energy conversion of TRCTP in tandem were analyzed and discussed to illustrate the effects. The experimental results indicate that the “sharp jump” phenomenon may appear at L/D = 2 and L/D = 3 significantly, with substantially increasing amplitude and decreasing oscillation frequency. The maximum amplitude ratio in the experiments is A*Max = 2.24, which appears after the “sharp jump” phenomenon at L/D = 3. In the present tests, the optimal active power Pharn = 21.04 W appears at L/D = 4 (Ur = 12.25, K = 2000 N/m, RL = 8 Ω), corresponding to the energy conversion efficiency ηharn = 4.67%.

The flow-induced rotational motion of tandem double cylinders has rarely been studied in existing papers. In order to further study the flow-induced rotation (FIR) of two mechanically tandem-coupled cylinders, an FIR device was designed in this paper, and the theoretical basis of this system was established. On this basis, a series of variable spacing ratio (L/D) tests were carried out in a recirculating water tunnel. The range of L/D was 4.0 ≤ L/D ≤ 9.0. The main experimental conclusions can be summarized as follows: (1) When L/D = 4.0 and 4.5, the rotational response was similar to vortex-induced vibration (VIV), which is different from typical VIV, in that the rotational oscillation would appear to be a re-growth region when velocitycontinued to increase after the oscillation entered the lower branch of VIV. Additionally, the oscillation was at a low level and the maximum arc length ratio (A*) was less than 0.55 in these two cases; (2) For L/D = 5.0, 5.5 and 6.0, the rotational responses all showed typical VIV. When the oscillation reached a high level, the maximum A* was more than 0.85 for each case; (3) When L/D = 7.0, 8.0 and 9.0, the rotational responses still presented typical VIV. The oscillation was at a medium level, and the maximum A* was between 0.53 and 0.72, but these three cases had a wider synchronization interval than the other cases, and the range showed an increasing trend with the growth of L/D.

Thymic blood vessels at the perivascular space (PVS) are the critical site for both homing of hematopoietic progenitor cells (HPCs) and egress of mature thymocytes. It has been intriguing how different opposite migrations can happen in the same place. A subset of specialized thymic portal endothelial cells (TPECs) associated with PVS has been identified to function as the entry site for HPCs. However, the cellular basis and mechanism underlying egress of mature thymocytes has not been well defined. In this study, using various conventional and conditional gene-deficient mouse models, we first confirmed the role of endothelial lymphotoxin beta receptor (LTβR) for thymic egress and ruled out the role of LTβR from epithelial cells or dendritic cells. In addition, we found that T cell-derived ligands lymphotoxin (LT) and LIGHT are required for thymic egress, suggesting a crosstalk between T cells and endothelial cells (ECs) for thymic egress control. Furthermore, immunofluorescence staining analysis interestingly showed that TPECs are also the exit site for mature thymocytes. Single-cell transcriptomic analysis of thymic endothelial cells suggested that TPECs are heterogeneous and can be further divided into two subsets depending on BST-1 expression level. Importantly, BST-1hi population is associated with thymic egressing thymocytes while BST-1lo/− population is associated with HPC settling. Thus, we have defined a LT/LIGHT-LTβR signaling–mediated cellular crosstalk regulating thymic egress and uncovered distinct subsets of TPECs controlling thymic homing and egress, respectively.

Sensorimotor transformation, a process that converts sensory stimuli into motor actions, is critical for the brain to initiate behaviors. Although the circuitry involved in sensorimotor transformation has been well delineated, the molecular logic behind this process remains poorly understood. Here, we performed high-throughput and circuit-specific single-cell transcriptomic analyses of neurons in the superior colliculus (SC), a midbrain structure implicated in early sensorimotor transformation. We found that SC neurons in distinct laminae expressed discrete marker genes. Of particular interest, Cbln2 and Pitx2 were key markers that define glutamatergic projection neurons in the optic nerve (Op) and intermediate gray (InG) layers, respectively. The Cbln2+ neurons responded to visual stimuli mimicking cruising predators, while the Pitx2+ neurons encoded prey-derived vibrissal tactile cues. By forming distinct input and output connections with other brain areas, these neuronal subtypes independently mediated behaviors of predator avoidance and prey capture. Our results reveal that, in the midbrain, sensorimotor transformation for different behaviors may be performed by separate circuit modules that are molecularly defined by distinct transcriptomic codes.

Abstract RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.

Background: We investigated whether serum levels of immunoglobin (Ig) E and Nε-carboxymethyl-lysine (CML) are related to in-stent restenosis (ISR) in patients with stable coronary artery disease and type 2 diabetes mellitus (T2DM). Methods: Serum levels of IgE and CML were measured in 196 ISR patients and 220 non-ISR patients with stable angina and T2DM who received angiographic follow-up 12 months after percutaneous coronary intervention (PCI) with third-generation drug-eluting stent (DES) implantation for de novo lesions. Multivariate logistic regression analysis was performed to assess the association between IgE or CML and ISR. Results: Both IgE and CML levels were higher in patients with ISR compared with non-ISR patients (IgE: 187.10 (63.75–489.65) vs. 80.25 (30.65–202.50), p < 0.001; CML: 203.26 (164.50–266.84) vs. 174.26 (130.85–215.56), p < 0.001). The rate of ISR increased stepwise with increasing tertiles of IgE and CML levels (p for all trends < 0.001), and IgE correlated significantly with CML. After adjusting for potential confounders, IgE and CML levels remained independently associated with ISR. Moreover, IgE and CML levels improved the predictive capability of traditional risk factors for ISR, and there existed an interaction between IgE and CML in relation to ISR (p for interaction < 0.01). Conclusion: Elevated circulating IgE and CML levels confer an increased risk for ISR after DES-based PCI in type 2 diabetic patients with stable coronary artery disease.

Spillway tunnels are key features in the regulation of the water surface of a reservoir and in ensuring the safety of life and properties of people downstream in a high dam project. This research aimed to provide a better understanding of the ventilation mechanism. The air–water two-phase flow was simulated under the Euler–Euler framework. A hybrid drag model, which was verified by the prototype data of Jinping-I spillway tunnel, was proposed to improve the prediction of air demand and air entrainment. The air demand prediction error was less than 18.9%, while the air entrainment prediction error was less than 28.35%. On the basis of the new drag model, the air entrainment behind aerators, air velocity distribution in the air ducts, and the residual space of the tunnel were systematically analyzed. Two flow patterns of the ventilation system were finally summarized.

Salinity acts as a critical environmental filter on microbial communities in natural systems, negatively affecting microbial diversity. However, how salinity affects microbial community assembly remains unclear. This study used Wendeng multi-pond saltern as a model to evaluate the prokaryotic community composition and diversity and quantify the relative importance of ecological processes across salinity gradients. The results showed that low-saline salterns (45–80 g/L) exhibited higher bacterial diversity than high-saline salterns (175–265 g/L). The relative abundance of taxa assigned to Halomicrobiaceae, Rhodobacteraceae, Saprospiraceae, and Thiotrichaceae exhibited a hump-shaped dependence on increasing salinity. Salinity and pH were the primary environmental factors that directly or indirectly determined the composition and diversity of prokaryotic communities. Microbial co-occurrence network dynamics were more complex in the sediment than in the water of salterns. An infer Community Assembly Mechanisms by Phylogenetic-bin-based null model analysis (iCAMP) showed that microbial community assembly in sediment and water differed. Our findings provide more information about microbial community structure and the importance of various ecological processes in controlling microbial community diversity and succession along salinity gradients in water and sediment.

Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoids (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of spontaneous excitatory postsynaptic currents (sEPSCs), spontaneous inhibitory postsynaptic currents (sIPSCs), and bidirectional electrical transmission indicated the presence of chemical and electrical synapses in vOrganoids. More importantly, single-cell RNA-sequencing analysis illustrated that vOrganoids exhibited robust neurogenesis and that cells of vOrganoids differentially expressed genes (DEGs) related to blood vessel morphogenesis. The transplantation of vOrganoids into the mouse S1 cortex resulted in the construction of functional human-mouse blood vessels in the grafts that promoted cell survival in the grafts. This vOrganoid culture method could not only serve as a model to study human cortical development and explore brain disease pathology but also provide potential prospects for new cell therapies for nervous system disorders and injury.

Summary: Cannabinoids are reported to rescue cocaine-induced seizures (CISs), a severe complication in cocaine users. However, the molecular targets for cannabinoid therapy of CISs remain unclear. Here, we report that the systemic administration of cannabinoids alleviates CISs in a CB1/CB2-receptor-independent manner. In HEK293 cells and cortical neurons, cocaine-induced dysfunction of the glycine receptor (GlyR) is restored by cannabinoids. Such restoration is blocked by GlyRα1S296A mutation. Consistently, the therapeutic effects of cannabinoids on CISs are also eliminated in GlyRα1S296A mutant mice. Based on molecular dynamic simulation, the hydrogen-bonding interaction between cocaine and the GlyR is weakened by cannabinoid docking. Without altering cocaine distribution across the brain, cannabinoids significantly suppress cocaine-exaggerated neuronal excitability in the prefrontal cortex (PFC) and hippocampus by rehabilitating extra-synaptic GlyR function. Microinjection of cannabinoids into the PFC and hippocampus restores cocaine-puzzled neural activity and alleviates CISs. These findings suggest that using GlyR-hypersensitive cannabinoids may represent a potential therapeutic strategy for treating CISs. : Zou et al. identify the glycine receptor as a potential therapeutic target for cannabinoids in treating cocaine-induced seizures. The function of extra-synaptic glycine receptors in the prefrontal cortex and hippocampus is impaired by cocaine and rescued by cannabinoids, therefore leading to the therapeutic effects of cannabinoids in treating cocaine-induced seizures. Keywords: cocaine, seizure, cannabinoids, glycine receptor, extra-synaptic, prefrontal cortex, hippocampus

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction， spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD.

Abstract The association between Zika virus (ZIKV) infection and congenital malformations such as microcephaly in infants is a public health emergency. Although various in vivo and in vitro models are used for ZIKV research, few animal models are available for resolving the effects of maternal ZIKV infection on neonatal development. Here, we established an immunocompetent mouse model via intrauterine inoculation. Our results confirmed that ZIKV, but not dengue virus, infection caused spontaneous abortions, brain malformations, ocular abnormalities, spinal cord defects and paralysis in mouse offspring. Aside from microcephaly and hippocampal dysplasia, eye abnormalities, including microphthalmia, thinner optic nerves, damaged retinae, and deficient visual projection, were also observed following ZIKV infection. Moreover, ZIKV-infected offspring showed a loss of alpha motor neurons in the spinal cord and cerebellar malformation, which may cause paralysis. ZIKV also impaired adult neurogenesis in neonatal mice. Due to its intact immunity, our rodent model can be used to systematically evaluate the impact of ZIKV on embryonic and neonatal development and to explore potential therapies.

Abstract The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.

The interplay between the low-energy carriers in Dirac materials and magnetism is likely to reveal many novel physical phenomena. Here, the authors use two-magnon Raman scattering to determine the exchange energies of two prototypical magnetic Dirac systems, CaMnBi2 and SrMnBi2.

Patients with liver diseases often suffer from chronic itch, yet the pruritogen(s) and receptor(s) remain largely elusive. Here, we identify bile acids as natural ligands for MRGPRX4. MRGPRX4 is expressed in human dorsal root ganglion (hDRG) neurons and co-expresses with itch receptor HRH1. Bile acids elicited Ca2+ responses in cultured hDRG neurons, and bile acids or a MRGPRX4 specific agonist induced itch in human subjects. However, a specific agonist for another bile acid receptor TGR5 failed to induce itch in human subjects and we find that human TGR5 is not expressed in hDRG neurons. Finally, we show positive correlation between cholestatic itch and plasma bile acids level in itchy patients and the elevated bile acids is sufficient to activate MRGPRX4. Taken together, our data strongly suggest that MRGPRX4 is a novel bile acid receptor that likely underlies cholestatic itch in human, providing a promising new drug target for anti-itch therapies.

Motivated by recent experimental and numerical progress on various cluster Mott insulators, we study an extended Hubbard model on a breathing kagome lattice with a single electron orbital and 1/6 electron filling. Two distinct types of cluster localization are found in the cluster Mott regime due to the presence of the electron repulsion between neighboring sites, rather than from the on-site Hubbard interaction in the conventional Mott insulators. We introduce a unified parton construction framework to accommodate both types of cluster Mott insulating phase as well as a trivial Ferm liquid metal and discuss the phase transitions in the phase diagram. It is shown that, in one of the cluster localization phases, the strong intersite repulsion results into locally metallic behavior within one of two triangular clusters on the breathing kagome lattice. We further comment on experimental relevance to existing Mo-based cluster magnets.

We point out the emergence of magnetism from the interplay of electron quasi-itinerancy and quantum order by disorder in pyrochlore iridates. Like other Mott insulating iridates, the Ir^{4+} ion in pyrochlore iridates develops an effective J=1/2 moment from the on-site spin-orbit coupling. We consider the generic symmetry-allowed exchange between these local moments on a pyrochlore lattice and obtain the mean-field phase diagram. Assuming the superexchange is mediated by direct and/or indirect electron hopping via intermediate oxygens, we derive the exchange interactions in the strong-coupling regime from the Hubbard model. This exchange has a degenerate classical ground-state manifold, and quantum fluctuation selects a noncoplanar ground state, known as quantum order by disorder. Extending to the intermediate-coupling regime, the same noncoplanar order is selected from the degenerate manifold by the kinetic energy, which is dubbed “electron quasi-itinerancy.” We discuss the experimental relevance of our results and electron quasi-itinerancy among other iridates and 4d/5d magnets.

Epigenetic regulation plays a key role in cortical development. Here the authors show that Rcor2, a co-repressor of the histone demethylase LSD1/KDM1A complex, regulates neural progenitor cell proliferation and cortical neurogenesis by repressing sonic hedgehog signaling.

The advantageous performance in terms of energy conversion for the flow-induced motion (FIM) of T-section prisms has been experimentally reported recently. In order to further understand the oscillation and energy conversion of multiple T-section prisms, a series of tests of two T-section prisms arranged in tandem with five different spacing ratios (3 ≤ L/D ≤ 15) and seven load resistances (8 Ω ≤ RL ≤ 41 Ω) were conducted. The effects of the spacing ratio and load resistances on energy conversion were discussed. The main conclusions can be summarized as follows. For most tests, the amplitudes of the upstream T-section prism (UTP) and downstream T-section prism (DTP) were both lower than the amplitude of the single T-section prism (STP) due to the mutual interference of the two prisms. Because of the mutual interference, the active powers of UTP and DTP were both less than that of STP, but at some special spacing ratios or load resistances, the mutual interference benefited the energy converted by the two prisms. In the presented tests, the total optimal active power of the upstream T-section prism and downstream T-section prism (UTP + DTP) was 30.12 W, which was 1.5 times that of STP (20.12 W).

Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding.