Long-Term Expansion of Pancreatic Islet Organoids from Resident Procr+ Progenitors.

It has generally proven challenging to produce functional ß cells in vitro. Here, we describe a previously unidentified protein C receptor positive (Procr+) cell population in adult mouse pancreas through single-cell RNA sequencing (scRNA-seq). The cells reside in islets, do not express differentiation markers, and feature epithelial-to-mesenchymal transition characteristics. By genetic lineage tracing, Procr+ islet cells undergo clonal expansion and generate all four endocrine cell types during adult homeostasis. Sorted Procr+ cells, representing ∼1% of islet cells, can robustly form islet-like organoids when cultured at clonal density. Exponential expansion can be maintained over long periods by serial passaging, while differentiation can be induced at any time point in culture. ß cells dominate in differentiated islet organoids, while α, δ, and PP cells occur at lower frequencies. The organoids are glucose-responsive and insulin-secreting. Upon transplantation in diabetic mice, these organoids reverse disease. These findings demonstrate that the adult mouse pancreatic islet contains a population of Procr+ endocrine progenitors.

Routes to high-performance layered oxide cathodes for sodium-ion batteries.

Sodium-ion batteries (SIBs) are experiencing a large-scale renaissance to supplement or replace expensive lithium-ion batteries (LIBs) and low energy density lead-acid batteries in electrical energy storage systems and other applications. In this case, layered oxide materials have become one of the most popular cathode candidates for SIBs because of their low cost and comparatively facile synthesis method. However, the intrinsic shortcomings of layered oxide cathodes, which severely limit their commercialization process, urgently need to be addressed. In this review, inherent challenges associated with layered oxide cathodes for SIBs, such as their irreversible multiphase transition, poor air stability, and low energy density, are systematically summarized and discussed, together with strategies to overcome these dilemmas through bulk phase modulation, surface/interface modification, functional structure manipulation, and cationic and anionic redox optimization. Emphasis is placed on investigating variations in the chemical composition and structural configuration of layered oxide cathodes and how they affect the electrochemical behavior of the cathodes to illustrate how these issues can be addressed. The summary of failure mechanisms and corresponding modification strategies of layered oxide cathodes presented herein provides a valuable reference for scientific and practical issues related to the development of SIBs.

An Intrinsic Stable Layered Oxide Cathode for Practical Sodium-Ion Battery: Solid Solution Reaction, Near-Zero-Strain and Marvelous Water Stability.

Non-aqueous solvents, in particular N,N-dimethylaniline (NMP), are widely applied for electrode fabrication since most sodium layered oxide cathode materials are readily damaged by water molecules. However, the expensive price and poisonousness of NMP unquestionably increase the cost of preparation and post-processing. Therefore, developing an intrinsically stable cathode material that can implement the water-soluble binder to fabricate an electrode is urgent. Herein, a stable nanosheet-like Mn-based cathode material is synthesized as a prototype to verify its practical applicability in sodium-ion batteries (SIBs). The as-prepared material displays excellent electrochemical performance and remarkable water stability, and it still maintains a satisfactory performance of 79.6% capacity retention after 500 cycles even after water treatment. The in situ X-ray diffraction (XRD) demonstrates that the synthesized material shows an absolute solid-solution reaction mechanism and near-zero-strain. Moreover, the electrochemical performance of the electrode fabricated with a water-soluble binder shows excellent long-cycling stability (67.9% capacity retention after 500 cycles). This work may offer new insights into the rational design of marvelous water stability cathode materials for practical SIBs.

Local white matter abnormalities in Parkinson's disease with mild cognitive impairment: Assessed with neurite orientation dispersion and density imaging.

Mild cognitive impairment is a nonmotor complication in Parkinson's disease (PD) that have a high risk of developing dementia. White matter is associated with cognitive function in PD and the alterations may occur before the symptoms of the disease. Previous diffusion tensor imaging (DTI) studies lacked specificity to characterize the concrete contributions of distinct white matter tissue properties. This may lead to inconsistent conclusions about the alteration of white matter microstructure. Here, we used neurite orientation dispersion and density imaging (NODDI) and white matter fiber clustering method to uncover local white matter microstructures in PD with mild cognitive impairment (PD-MCI). This study included 23 PD-MCI and 20 PD with normal cognition (PD-NC) and 21 healthy controls (HC). To probe specific and fine-grained differences, metrics of NODDI and DTI in white matter fiber clusters were evaluated using along-tract analysis. Our results showed that PD-MCI patients had significantly lower neurite density index (NDI) and orientation dispersion index (ODI) in white matter fiber clusters in the prefrontal region. Correlation analysis and receiver operating characteristic (ROC) analysis revealed that the diagnostic performance of NODDI-derived metrics in cingulum bundle (2 clusters) and thalamo-frontal (2 clusters) were superior to DTI metrics. Our study provides a more specific insight to uncover local white matter abnormalities in PD-MCI, which benefit understanding the underlying mechanism of cognitive decline in PD and predicting the disease in advance.

Alterations of white matter tracts and topological properties of structural networks in hemifacial spasm.

Hemifacial spasm (HFS) is characterized by involuntary and paroxysmal muscle contractions on the hemiface. It is generally believed that HFS is caused by neurovascular compression at the root exit zone of the facial nerve. In recent years, the structural alterations of brains with HFS have aroused growing concern. However, little attention has been directed towards the possible involvement of specific white matter (WM) tracts and the topological properties of structural networks in HFS. In the present study, diffusion magnetic resonance imaging tractography was utilized to construct structural networks and perform tractometric analysis. The diffusion tensor imaging scalar parameters along with the WM tracts, and the topological parameters of global networks and subnetworks, were assessed in 62 HFS patients and 57 demographically matched healthy controls (HCs). Moreover, we investigated the correlation of these parameters with disease-clinical-level (DCL) and disease-duration-time (DDT) of HFS patients. Compared with HCs, HFS patients had additional hub regions including the amygdala, ventromedial putamen, lateral occipital cortex, and rostral cuneus gyrus. Furthermore, HFS patients showed significant alternations with specific topological properties in some structural subnetworks, including the limbic, default mode, dorsal attention, somato-motor, and control networks, as well as diffusion properties in some WM tracts, including the superior longitudinal fasciculus, cingulum bundle, thalamo-frontal, and corpus callosum. These subnetworks and tracts were associated with the regulation of emotion, motor function, vision, and attention. Notably, we also found that the parameters with subnetworks and tracts exhibited correlations with DCL and DDT. In addition to corroborating previous findings in HFS, this study demonstrates the changed microstructures in specific locations along with the fiber tracts and changed topological properties in structural subnetworks.

Phosphorylation of Msx1 promotes cell proliferation through the Fgf9/18-MAPK signaling pathway during embryonic limb development.

Msh homeobox (Msx) is a subclass of homeobox transcriptional regulators that control cell lineage development, including the early stage of vertebrate limb development, although the underlying mechanisms are not clear. Here, we demonstrate that Msx1 promotes the proliferation of myoblasts and mesenchymal stem cells (MSCs) by enhancing mitogen-activated protein kinase (MAPK) signaling. Msx1 directly binds to and upregulates the expression of fibroblast growth factor 9 (Fgf9) and Fgf18. Accordingly, knockdown or antibody neutralization of Fgf9/18 inhibits Msx1-activated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation. Mechanistically, we determined that the phosphorylation of Msx1 at Ser136 is critical for enhancing Fgf9 and Fgf18 expression and cell proliferation, and cyclin-dependent kinase 1 (CDK1) is apparently responsible for Ser136 phosphorylation. Furthermore, mesenchymal deletion of Msx1/2 results in decreased Fgf9 and Fgf18 expression and Erk1/2 phosphorylation, which leads to serious defects in limb development in mice. Collectively, our findings established an important function of the Msx1-Fgf-MAPK signaling axis in promoting cell proliferation, thus providing a new mechanistic insight into limb development.

Automated facial-vestibulocochlear nerve complex identification based on data-driven tractography clustering.

Small size and intricate anatomical environment are the main difficulties facing tractography of the facial-vestibulocochlear nerve complex (FVN), and lead to challenges in fiber orientation distribution (FOD) modeling, fiber tracking, region-of-interest selection, and fiber filtering. Experts need rich experience in anatomy and tractography, as well as substantial labor costs, to identify the FVN. Thus, we present a pipeline to identify the FVN automatically, in what we believe is the first study of the automated identification of the FVN. First, we created an FVN template. Forty high-resolution multishell data were used to perform data-driven fiber clustering based on the multishell multitissue constraint spherical deconvolution FOD model and deterministic tractography. We selected the brainstem and cerebellum (BS-CB) region as the seed region and removed the fibers that reach other brain regions. We then performed spectral fiber clustering twice. The first clustering was to create a BS-CB atlas and separate the fibers that pass through the cerebellopontine angle, and the other one was to extract the FVN. Second, we registered the subject-specific fibers in the space of the FVN template and assigned each fiber to the closest cluster to identify the FVN automatically by spectral embedding. We applied the proposed method to different acquirement sites, including two different healthy datasets and two tumor patient datasets. Experimental results showed that our automatic identification results have ideal colocalization with expert manual identification in terms of spatial overlap and visualization. Importantly, we successfully applied our method to tumor patient data. The FVNs identified by the proposed method were in agreement with intraoperative findings.

Msx1 cooperates with Runx1 for inhibiting myoblast differentiation.

Myogenesis is an important and complicated biological process, especially during the process of embryonic development. The homeoprotein Msx1 is a crucial transcriptional repressor of myogenesis and maintains myogenic precursor cells in an undifferentiated, proliferative state. However, the molecular mechanism through which Msx1 coordinates myogenesis remains to be elucidated. Here, we determine the interacting partner proteins of Msx1 in myoblast cells by a proteomic screening method. Msx1 is found to interact with 55 proteins, among which our data demonstrate that the cooperation of Runt-related transcription factor 1 (Runx1) with Msx1 is required for myoblast cell differentiation. Our findings provide important insights into the mechanistic roles of Msx1 in myoblast cell differentiation, and lays foundation for the myogenic differentiation process.

New Measures for the Coronavirus Disease 2019 Response: A Lesson From the Wenzhou Experience.

As the outbreak of coronavirus disease 2019 (COVID-19) has spread globally, determining how to prevent the spread is of paramount importance. We reported the effectiveness of different responses of 4 affected cities in preventing the COVID-19 spread. We expect the Wenzhou anti-COVID-19 measures may provide information for cities around the world that are experiencing this epidemic.

Association of Web-Based Physical Education With Mental Health of College Students in Wuhan During the COVID-19 Outbreak: Cross-Sectional Survey Study.

BACKGROUND: The COVID-19 outbreak has affected people's health worldwide. For college students, web-based physical education is a challenge, as these course are normally offered outdoors. OBJECTIVE: The aim of this study was to use data from a web-based survey to evaluate the relationship between the mental health status of college students and their sports-related lifestyles. Problems related to web-based physical education were also examined. METHODS: A web-based survey was conducted by snowball sampling from May 8 to 11, 2020. Demographic data, mental health status, and sports-related lifestyles of college students in Wuhan as well as issues related to web-based physical education were collected. Mental health status was assessed by the Depression, Anxiety, and Stress Scale (DASS-21). RESULTS: The study included 1607 respondents from 267 cities. The average scores of the DASS-21 subscales (2.46 for depression, 1.48 for anxiety, and 2.59 for stress) were significantly lower in our study than in a previous study (P<.05). Lower DASS-21 scores were significantly correlated with regular exercise, maintaining exercise habits during the outbreak of COVID-19, exercising more than 1 to 2 times a week, exercise duration >1 hour, and >2000 pedometer steps (all P<.05). None of the three forms of web-based physical education was preferred by more than 50% of respondents. Frequent technical problems were confronted by 1087/1607 students (67.6%). Shape-up exercises (846/1607, 52.6%), a designed combination of exercises (710/1607, 44.2%), and Chinese kung fu (559/1607, 34.8%) were suggested sports for web-based physical education. CONCLUSIONS: Mental status was significantly correlated with regular exercise and sufficient exercise duration. Professional physical guidance is needed for college students in selected sports. Exercises not meeting students' preferences, frequent technical problems, and the distant interaction involved in web-based physical education were the main problems that should be solved in future.

Protein C receptor stimulates multiple signaling pathways in breast cancer cells.

The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and transactivation of insulin-like growth factor 1 receptor (IGF-1R). These pathway activities led to the accumulation of c-Myc and cyclin D1. On the other hand, PROCR-dependent RhoA-ROCK-p38 signaling relied on coagulation factor II thrombin receptor (F2R). We confirmed these findings in primary cells isolated from triple-negative breast cancer-derived xenografts (PDX) that have high expression of PROCR. To the best our knowledge, this is the first comprehensive study of PROCR signaling in breast cancer cells, and its findings also shed light on the molecular mechanisms of PROCR in stem cells in normal tissue.

Loss of homeoprotein Msx1 and Msx2 leading to athletic and kinematic impairment related to the increasing neural excitability of neurons in aberrant neocortex in mice.

Although homeoproteins Msx1 and Msx2, the cell-specific transcription regulators, have been proven to play multiple roles in the embryogenesis of bone, muscle and tooth, the functions and mechanisms of Msx1 and Msx2 in the development of the central nervous system of mice after birth are not clear because of the death of Msx1 and Msx1/2 germline-deleted embryo at late gestation of mouse. In current research, Nestin-Cre mice was introduced to generate the central nervous system-specific knockout mice (Nestin-Cre;Msx1,Msx2fl/fl). We found that besides the falling of the body mass and the brain volume, the cortical tissue sections and staining showed the decreasing thickness of layer II-IV and declining number of vertebral cells in layer V resulting from Msx1/2 deletion. In addition, electrophysiological tests revealed the aberrant action potential parameters of deep pyramidal neurons in Nestin-Cre;Msx1,2 fl/fl mice, which may be related with the ethology impairment displayed in further experiments. We discovered Nestin-Cre;Msx1,2 fl/fl mice had severe impairment in their athletic ability and kinematic learning ability in rotate test, and exhibited hyperactivity in open-field test. Above all, our results revealed that deletion of homeoproteins Msx1 and Msx2 could lead to behavioral disorders and suggested that Msx1 and Msx2 played a crucial role in regulating the development and function of the neocortex. In addition, our current research provided a new mouse model for understanding the pathogenesis of human central nervous system disease.

Facilitating Layered Oxide Cathodes Based on Orbital Hybridization for Sodium-Ion Batteries: Marvelous Air Stability, Controllable High Voltage, and Anion Redox Chemistry.

Layered oxides have become the research focus of cathode materials for sodium-ion batteries (SIBs) due to the low cost, simple synthesis process, and high specific capacity. However, the poor air stability, unstable phase structure under high voltage, and slow anionic redox kinetics hinder their commercial application. In recent years, the concept of manipulating orbital hybridization has been proposed to simultaneously regulate the microelectronic structure and modify the surface chemistry environment intrinsically. In this review, the hybridization modes between atoms in 3d/4d transition metal (TM) orbitals and O 2p orbitals near the region of the Fermi energy level (EF) are summarized based on orbital hybridization theory and first-principles calculations as well as various sophisticated characterizations. Furthermore, the underlying mechanisms are explored from macro-scale to micro-scale, including enhancing air stability, modulating high working voltage, and stabilizing anionic redox chemistry. Meanwhile, the origin, formation conditions, and different types of orbital hybridization, as well as its application in layered oxide cathodes are presented, which provide insights into the design and preparation of cathode materials. Ultimately, the main challenges in the development of orbital hybridization and its potential for the production application are also discussed, pointing out the route for high-performance practical sodium layered oxide cathodes.

Investigation into white matter microstructure differences in visual training by using an automated fiber tract subclassification segmentation quantification method.

Visual training has emerged as a useful framework for investigating training-related brain plasticity, a highly complex task involving the interaction of visual orientation, attention, reasoning, and cognitive functions. However, the effects of long-term visual training on microstructural changes within white matter (WM) is poorly understood. Therefore, a set of visual training programs was designed, and automated fiber tract subclassification segmentation quantification based on diffusion magnetic resonance imaging was performed to obtain the anatomical changes in the brains of visual trainees. First, 40 healthy matched participants were randomly assigned to the training group or the control group. The training group underwent 10 consecutive weeks of visual training. Then, the fiber tracts of the subjects were automatically identified and further classified into fiber clusters to determine the differences between the two groups on a detailed scale. Next, each fiber cluster was divided into segments that can analyze specific areas of a fiber cluster. Lastly, the diffusion metrics of the two groups were comparatively analyzed to delineate the effects of visual training on WM microstructure. Our results showed that there were significant differences in the fiber clusters of the cingulate bundle, thalamus frontal, uncinate fasciculus, and corpus callosum between the training group compared and the control group. In addition, the training group exhibited lower mean fractional anisotropy, higher mean diffusivity and radial diffusivity than the control group. Therefore, the long-term cognitive activities, such as visual training, may systematically influence the WM properties of cognition, attention, memory, and processing speed.

Nickel Nanoparticles Protruding from Molybdenum Carbide Micropillars with Carbon Layer-Protected Biphasic 0D/1D Heterostructures for Efficient Water Splitting.

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo2C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H2 and C2H2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo2C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm-2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo2C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo2C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.

Developing an abnormal high-Na-content P2-type layered oxide cathode with near-zero-strain for high-performance sodium-ion batteries.

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

Physical activity, problematic smartphone use, and burnout among Chinese college students.

The aim of this study was to investigate the association between physical activity (PA), problematic smartphone use (PSU), and burnout, as well as to identify whether there is a mediating role for PSU. We recruited 823 college students (Mage = 18.55, SD = 0.83) from Wuhan, China, in December 2022, including 499 males and 324 females. Demographic information, the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Smartphone Addiction Scale-Short Version (SAS-SV), and the Maslach Burnout Inventory-Student Survey (MBI-SS) were used for assessments. Pearson correlation analysis showed that PA was significantly associated with PSU (r = -0.151, p < 0.001), PSU was significantly associated with burnout (r = 0.421, p < 0.001), and the association between PA and burnout was not statistically significant (r = -0.046, p > 0.05). The results of the mediation model test showed that PA could not predict burnout directly; it instead predicted burnout entirely indirectly through PSU. Furthermore, PSU mediated the predictive effect of PA on exhaustion and cynicism. In conclusion, there is no direct connection between PA levels and burnout. PA indirectly affects burnout through PSU, but does not fully apply to the three different dimensions of exhaustion, cynicism, and professional efficacy.

A Universal Strategy Based on Bridging Microstructure Engineering and Local Electronic Structure Manipulation for High-Performance Sodium Layered Oxide Cathodes.

Due to their high capacity and sufficient Na+ storage, O3-NaNi0.5Mn0.5O2 has attracted much attention as a viable cathode material for sodium-ion batteries (SIBs). However, the challenges of complicated irreversible multiphase transitions, poor structural stability, low operating voltage, and an unstable oxygen redox reaction still limit its practical application. Herein, using O3-NaNi0.5Mn0.5-xSnxO2 cathode materials as the research model, a universal strategy based on bridging microstructure engineering and local electronic structure manipulation is proposed. The strategy can modulate the physical and chemical properties of electrode materials, so as to restrain the unfavorable and irreversible multiphase transformation, improve structural stability, manipulate redox potential, and stabilize the anion redox reaction. The effect of Sn substitution on the intrinsic local electronic structure of the material is articulated by density functional theory calculations. Meanwhile, the universal strategy is also validated by Ti substitution, which could be further extrapolated to other systems and guide the design of cathode materials in the field of SIBs.

Sodium Layered/Tunnel Intergrowth Oxide Cathodes: Formation Process, Interlocking Chemistry, and Electrochemical Performance.

Manganese-based layered oxides are prospective cathode materials for sodium-ion batteries (SIBs) due to their low cost and high theoretical capacities. The biphasic intergrowth structure of layered cathode materials is essential for improving the sodium storage performance, which is attributed to the synergistic effect between the two phases. However, the in-depth formation mechanism of biphasic intergrowth materials remains unclear. Herein, the layered/tunnel intergrowth Na0.6MnO2 (LT-NaMO) as a model material was successfully prepared, and their formation processes and electrochemical performance were systematically investigated. In situ high-temperature X-ray diffraction displays the detailed evolution process and excellent thermal stability of the layered/tunnel intergrowth structure. Furthermore, severe structural strain and large lattice volume changes are significantly mitigated by the interlocking effect between the phase interfaces, which further enhances the structural stability of the cathode materials during the charging/discharging process. Consequently, the LT-NaMO cathode displays fast Na+ transport kinetics with a remarkable capacity retention of ∼70.5% over 300 cycles at 5C, and its assembled full cell with hard carbon also exhibits high energy density. These findings highlight the superior electrochemical performance of intergrowth materials due to interlocking effects between layered and tunnel structures and also provide unique insights into the construction of intergrowth cathode materials for SIBs.

Metaphorical or Straightforward? Comparing the Effectiveness of Different Types of Social Media Advertising.

The existing studies have analyzed the advertising effects of metaphorical advertisements and straightforward adverts in traditional advertising media. However, their advertising effects on social media are still unclear. To address this issue, this study uses eye-tracking and questionnaires to examine two types of social media tourism advertising-metaphorical and straightforward in posts with both high and low popularity. This within-subject (n = 55) experiment was designed to examine the effects of social media tourism advertising types on visual attention and tourism intention and to identify the moderating role of post popularity based on the elaboration likelihood model (ELM). We found that advertising types had no significant effect on visual attention, but metaphorical advertisements increased tourism intention compared with straightforward adverts. Furthermore, we found that the level of post popularity moderated the effect of advertising types on visual attention. Specifically, metaphorical adverts in highly popular posts attracted more visual attention in the advertising text area and in the whole advert. Straightforward adverts in posts with low popularity attracted more visual attention in the advertising text area. This research advances the current literature by exploring the effects of social media tourism advertising types and has implications for managers deciding on strategies for social media tourism marketing.