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Few studies examined the association of energy, macronutrients and food consumption at dinner v. breakfast with hypercholesterolaemia. A total of 27 911 participants from the National Health and Nutrition Examination Survey (2003–2016) were included in the cross-sectional study. Energy, macronutrients and food consumption at breakfast, dinner and the difference at dinner v. breakfast (Δratio) were calculated. Multiple logistic regression models and substitution effects of foods at dinner with breakfast were also performed. After adjustment for potential covariates, compared with the lowest quintile, participants in the highest quintile of Δratio in terms of energy had a higher risk of prevalent hypercholesterolaemia (ORΔratio of energy 1·16, 95 % CI (1·01, 1·33)) mainly due to Δratio of low-quality carbohydrates and plant protein (ORΔratio of low-quality carbohydrates 1·19; 95 % CI (1·05, 1·35)); ORΔratio of plant protein 1·13; 95 % CI (1·01, 1·28)). ΔAdded sugars and Δnuts were associated with hypercholesterolaemia (ORΔadded sugars 1·01; 95 % CI (1·00, 1·02)); ORΔnuts 1·08; 95 % CI (1·01, 1·16)). Furthermore, the substitution of added sugars, nuts and processed meat at dinner with breakfast could reduce the OR of hypercholesterolaemia. This study indicated that among US adults, overconsumption of energy, macronutrients including low-quality carbohydrates and plant protein at dinner than breakfast was significantly associated with a higher risk of prevalent hypercholesterolaemia. The replacing of added sugar, nuts and processed meat at dinner with breakfast reduced the risk of prevalent hypercholesterolaemia. This study emphasised the importance of meal timing in the prevention of hypercholesterolaemia.

The etiology and pathology of autism spectrum disorders (ASDs) are still poorly understood, which largely limit the treatment and diagnosis of ASDs. Emerging evidence supports that abnormal metabolites in the cerebral cortex of a BTBR mouse model of autism are involved in the pathogenesis of autism. However, systematic study on global metabolites in the cerebral cortex of BTBR mice has not been conducted. The current study aims to characterize metabolic changes in the cerebral cortex of BTBR mice by using an untargeted metabolomic approach based on UPLC-Q-TOF/MS. C57BL/6 J mice were used as a control group. A total of 14 differential metabolites were identified. Compared with the control group, the intensities of PI(16:0/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/18:1(9Z)), PA(16:0/18:1(11Z)), 17-beta-estradiol-3-glucuronide, and N6,N6,N6-trimethyl-L-lysine decreased significantly (p 0.01) and the intensities of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline, LysoPC(20:4(5Z,8Z,11Z,14Z)/0:0), adenosine monophosphate, adenosine-5'-phosphosulfate, LacCer(d18:1/12:0),3-dehydro-L-gulonate, N-(1-deoxy-1-fructosyl)tryptophan, homovanillic acid, and LPA(0:0/18:1(9Z)) increased significantly (p 0.01) in the BTBR group. These changes in metabolites were closely related to perturbations in lipid metabolism, energy metabolism, purine metabolism, sulfur metabolism, amino acid metabolism, and carnitine biosynthesis. Notably, exacerbation of the oxidative stress response caused by differential prooxidant metabolites led to alteration of antioxidative systems in the cerebral cortex and resulted in mitochondrial dysfunction, further leading to abnormal energy metabolism as an etiological mechanism of autism. A central role of abnormal metabolites in neurological functions associated with behavioral outcomes and disturbance of sulfur metabolism and carnitine biosynthesis were found in the cerebral cortex of BTBR mice, which helped increase our understanding for exploring the pathological mechanism of autism.

Waterfront intervention, as one of the post-industrial reuse paradigms, has flourished around the world and been studied as a global phenomenon. This paper investigates the application of a dual adaptive reuse strategy to industrial heritage waterfront buildings and explores its social significance. The case study is of the West Bund, a waterfront renovation in Shanghai, China. Insights are drawn from the qualitative research approach of triangulation, with evidence derived from document sources, archival records, direct participants and semi-structured interviews. This paper examines a series of galleries and landscapes created from former industrial buildings and facilities along the Huangpu River. It concludes that the West Bund exemplifies a dual strategy of adaptive reuse: art-led and landscape-led building reuse. This dual strategy can be viewed as an endeavour to balance urban gentrification and publicness in the megalopolis. It can also be argued, however, that the dual approach to adaptive reuse is unsustainable within the framework of an entrepreneurial state, and significantly so in the post-epidemic era when economic growth pressure increases. This study contributes to our understanding of the complex nature of industrial heritage in the rapidly shifting landscape of contemporary China.

Irritable bowel syndrome (IBS) is a common functional digestive tract disease worldwide, with a high prevalence among medical staff. The purpose of this study is to systematically evaluate the prevalence and influencing factors of IBS in medical staff.We searched English online databases, including PubMed, The Cochrane Library, Web of Science, Embase, and EBSCOhost. The retrieval time was from database establishment to May of 2021. We screened the literature according to inclusion and exclusion criteria, extracted the relevant information, and evaluated the research quality. A meta-analysis was performed using the Stata 16.0 and Review Manager 5.4.1 software.A total of 11 English studies from seven countries were included in this study, including 3,360 medical staff. The results of the meta-analysis showed an overall prevalence of IBS among medical staff of 16% [95%CI (0.15 ~ 0.17)] and that shift work (OR 2.27)), poor sleep quality (OR 4.27), and female gender (OR 2.29) are the major influencing factors of medical staff suffering from IBS.The prevalence of irritable bowel syndrome among medical staff is relatively high, and hospitals can start by looking for targeted interventions from the highly related factors of IBS among medical staff such as shift work patterns, females, and poor sleep quality.

To decipher the organizational logic of complex brain circuits, it is important to chart long-distance pathways while preserving micron-level accuracy of local network. However, mapping the neuronal projections with individual-axon resolution in the large and complex primate brain is still challenging. Herein, we describe a highly efficient pipeline for three-dimensional mapping of the entire macaque brain with subcellular resolution. The pipeline includes a novel poly-N-acryloyl glycinamide (PNAGA)-based embedding method for long-term structure and fluorescence preservation, high-resolution and rapid whole-brain optical imaging, and image post-processing. The cytoarchitectonic information of the entire macaque brain was acquired with a voxel size of 0.32 μm × 0.32 μm × 10 μm, showing its anatomical structure with cell distribution, density, and shape. Furthermore, thanks to viral labeling, individual long-distance projection axons from the frontal cortex were for the first time reconstructed across the entire brain hemisphere with a voxel size of 0.65 μm × 0.65 μm × 3 μm. Our results show that individual cortical axons originating from the prefrontal cortex simultaneously target multiple brain regions, including the visual cortex, striatum, thalamus, and midbrain. This pipeline provides an efficient method for cellular and circuitry investigation of the whole macaque brain with individual-axon resolution, and can shed light on brain function and disorders.

Malignant melanoma, an increasingly common form of skin cancer, is a major threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. Targeted drug development is an effective strategy for the treatment of malignant melanoma. In this work, a new antimelanoma tumor peptide, the lebestatin–annexin V (designated LbtA5) fusion protein, was developed and synthesized by recombinant DNA techniques. As a control, annexin V (designated ANV) was also synthesized by the same method. The fusion protein combines annexin V, which specifically recognizes and binds phosphatidylserine, with the disintegrin lebestatin (lbt), a polypeptide that specifically recognizes and binds integrin α1β1. LbtA5 was successfully prepared with good stability and high purity while retaining the dual biological activity of ANV and lbt. MTT assays demonstrated that both ANV and LbtA5 could reduce the viability of melanoma B16F10 cells, but the activity of the fusion protein LbtA5 was superior to that of ANV. The tumor volume growth was slowed in a mouse xenograft model treated with ANV and LbtA5, and the inhibitory effect of high concentrations of LbtA5 was significantly better than that of the same dose of ANV and was comparable to that of DTIC, a drug used clinically for melanoma treatment. The hematoxylin and eosin (H&E) staining test showed that ANV and LbtA5 had antitumor effects, but LbtA5 showed a stronger ability to induce melanoma necrosis in mice. Immunohistochemical experiments further showed that ANV and LbtA5 may inhibit tumor growth by inhibiting angiogenesis in tumor tissue. Fluorescence labeling experiments showed that the fusion of ANV with lbt enhanced the targeting of LbtA5 to mouse melanoma tumor tissue, and the amount of target protein in tumor tissue was significantly increased. In conclusion, effective coupling of the integrin α1β1-specific recognition molecule lbt confers stronger biological antimelanoma effects of ANV, which may be achieved by the dual effects of effective inhibition of B16F10 melanoma cell viability and inhibition of tumor tissue angiogenesis. The present study describes a new potential strategy for the application of the promising recombinant fusion protein LbtA5 in the treatment of various cancers, including malignant melanoma.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input–output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture., Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

The cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1–4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico–basal ganglia–thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico– basal ganglia–thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop., Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

Tree resistance to overturning is crucial in forestry hazard applications and management. Tree anchorage varies considerably with species, tree age, and site conditions. We investigate the relationship between the root characteristics of the overturning slip surface and the role of roots (regarding different diameters in overturning). Four Leucaena leucocephala were fully excavated by a quadrate monolith to establish root distribution characteristics, and 19 L. leucocephala were uprooted until the trees completely overturned to measure the anchoring resistance to overturning. A model was developed to improve the descriptions of root characteristics in the mechanical processes for tree overturning. The results show that the distribution characteristics of the root system were well described by the model. For the root–soil plate radius, the thickest root diameter and the root biomass of different diameters at the overturning slip surface increased with the diameter at the breast height. The root biomass affected the strength of the overturning slip surface; the root density may be a key factor in identifying the location of the overturning slip surface. The model could predict the overturning moment of most overturned trees; although it overestimated the overturning moment for small diameters at breast height trees, the results will be useful for understanding the influence of root distribution characteristics in overturning.

We aimed to determine the association between distinct body mass index (BMI) trajectories, using group-based trajectory modeling, and the subsequent risk of incident diabetes. Five databases were systematically searched. Fourteen population-based cohort studies that summarized the association between different BMI trajectories and subsequent diabetes, with the four most common BMI trajectories including the "stable," "increasing," "decreasing," and "turning" groups, were included. The rapid increase and stable high-level BMI groups showed the strongest association with the subsequent risk of diabetes compared with the stable normal BMI group. Increased baseline BMI levels resulted in a steeper slope and greater risk of subsequent diabetes. In the decreasing BMI group, one study reported that those agedgt;50 years showed the highest incidence of subsequent diabetes, whereas the other two studies reported no association between these two variables. In the turning group, an increase followed by a decrease in BMI levels from adolescence to late adulthood could reduce the risk of developing diabetes, although the residual risk remained. By contrast, the incidence of subsequent diabetes remained high in the middle-aged BMI-turning group. This study can provide further insights for identifying populations at high risk of diabetes and for developing targeted prevention strategies.

Through synaptic connections, long-range circuits transmit information among neurons and connect different brain regions to form functional motifs and execute specific functions. Tracing the synaptic distribution of specific neurons requires submicron-level resolution information. However, it is a great challenge to map the synaptic terminals completely because these fine structures span multiple regions, even in the whole brain. Here, we develop a pipeline including viral tracing, sample embedding, fluorescent micro-optical sectional tomography, and big data processing. We mapped the whole-brain distribution and architecture of long projections of the parvalbumin neurons in the basal forebrain at the synaptic level. These neurons send massive projections to multiple downstream regions with subregional preference. With three-dimensional reconstruction in the targeted areas, we found that synaptic degeneration was inconsistent with the accumulation of amyloid-β plaques but was preferred in memory-related circuits, such as hippocampal formation and thalamus, but not in most hypothalamic nuclei in 8-month-old mice with five familial Alzheimer’s disease mutations. Our pipeline provides a platform for generating a whole-brain atlas of cell-type-specific synaptic terminals in the physiological and pathological brain, which can provide an important resource for the study of the organizational logic of specific neural circuits and the circuitry changes in pathological conditions.

At present, the international evaluation method of loess collapsibility only evaluates loess once collapses, but some scholars have found that loess is characterized with the phenomenon of repeated collapsibility under certain conditions. To explore the characteristics of repeated collapsibility of loess and to find a simple and feasible method for evaluating repeated collapsibility of loess, this paper selects soil samples with different water content for repeated compression tests. Loess is a typical structural soil, and its structure is significantly weakened by water and pressure. This paper combines three main parameters influencing the structure of loess to define a comprehensive physical index and explores the relationship between the comprehensive physical index and the structural yield strength of loess under repeated collapsibility. Using the structural yield strength of loess to normalize the compression curve during repeated collapse, a method for evaluating repeated collapsing of loess has been proposed. This method combines the compression index of loess with the basic physical parameters of loess, which is more suitable for evaluating the repeated collapsibility of loess. By comparing the calculation results with the measured results, it was determined that this method has high accuracy. This method was used to calculate the coefficient of collapsibility of Guyuan loess, and the results show that loess with a moisture content of

The bound state in the continuum (BIC) is a singular point of polarization in the momentum space of a periodic structure. It has been demonstrated that vortex beams can be generated by utilizing the polarization vortex around BIC based on the geometric phase in momentum space. In this letter, we propose a reflective photonic crystal (PhC) to generate a vortex beam and demonstrate the superimposition of topological charges in the momentum space between PhC and the vortex beams. In addition to BICs, we demonstrate that other singularities like degenerate points can also be used to generate vortex beams.

In order to help architects Reduce energy consumption in buildings more pertinently in the early stage of design, this paper takes high-rise hotels in Guangdong as a research subject, obtains the building characteristic factor data of 28 groups of hotel samples through investigation, successively models and simulates the energy consumption value in Energy Plus software, and then studies the energy consumption characteristics and influencing factors of hotel buildings in Guangdong through the simulation results. Results show that the plane type has little effect on the energy consumption per unit area, and the standard floor area, the standard floor height and the four-way window wall ratio have a greater impact on the total energy consumption of the building. Except for the standard floor area, other building characteristics have a positive correlation with the total energy consumption per unit area.

The impressive functions of the brain rely on an extensive connectivity matrix between specific neurons, the architecture of which is frequently characterized by one brain nucleus/region connecting to multiple targets, either via collaterals of the same projection neuron or several, differentially specified neurons. Delineating the fine architecture of projection neuron subsets in a specific brain region could greatly facilitate its circuit, computational, and functional resolution. Here, we developed multiple fluorescent rabies viruses (RV) to delineate the fine organization of corticothalamic projection neuron subsets in the primary visual cortex (V1). By simultaneously retrograde labeling multiple distinct subsets of corticothalamic projection neurons in V1 from their target nuclei in thalamus (dLGN, LP, LD), we observed that V1-dLGN corticothalamic projection neurons were densely concentrated in layer VI, except for several sparsely scattered neurons in layer V, while V1-LP and V1-LD corticothalamic projection neurons were localized to both layers V and VI. Meanwhile, we observed a fraction of V1 corticothalamic projection neurons targeting two thalamic nuclei, which was further confirmed by fMOST whole-brain imaging. The multiple fluorescent RV tracing tools can be extensively applied to resolve the architecture of projection neuron subsets in certain brain regions, with a strong potential to delineate the computational and functional organization of these brain regions.

The microscopic visualization of large-scale three-dimensional (3D) samples by optical microscopy requires overcoming challenges in imaging quality and speed and in big data acquisition and management. We report a line-illumination modulation (LiMo) technique for imaging thick tissues with high throughput and low background. Combining LiMo with thin tissue sectioning, we further develop a high-definition fluorescent micro-optical sectioning tomography (HD-fMOST) method that features an average signal-to-noise ratio of 110, leading to substantial improvement in neuronal morphology reconstruction. We achieve a >30-fold lossless data compression at a voxel resolution of 0.32 × 0.32 × 1.00 μm3, enabling online data storage to a USB drive or in the cloud, and high-precision (95% accuracy) brain-wide 3D cell counting in real time. These results highlight the potential of HD-fMOST to facilitate large-scale acquisition and analysis of whole-brain high-resolution datasets. HD-fMOST is a microscopy technique for imaging large samples at high throughput and with high definition, which is achieved with a line-illumination modulation approach. The technology is illustrated by imaging fluorescently labeled neurons in whole mouse brains.

Supramolecular hydrogels attract extensive attention as waterborne biocompatible materials like biological tissues. Here we developed poly[N-(2-acetamidoethyl)acrylamide] (PAAE) supramolecular hydrogels with multiple hydrogen bonds, which exhibit ideal mechanical performances, such as strong resistance to compression and stretch, high stability in acidic or high ionic strength solution, excellent waterborne adhesiveness, self-healing and swelling behaviors. The small molecular precursor for PAAE hydrogels possesses great solubility up to 70 wt% in deionized water and superior infiltration capability to mouse brain tissues at 5 °C, and can be in situ polymerized at 30–45 °C and swollen in deionized water with a 1.75 times linear expansion factor. There is no noticeable loss of fluorescence intensity during the whole process from small molecular infiltration and polymerization to expansion. The mouse brain slices were embedded and used for expansion microscopy with enhanced optical resolution and preserved structure integrity.

Nasopharyngeal carcinoma (NPC) is one kind of human head and neck cancers with high incidence in Southern China, Southeast Asia and North Africa. In spite of great innovations in radiation and chemotherapy treatments, the 5-year survival rate is not satisfactory. One of the main reasons is resistance to radiotherapy which leads to therapy failure and recurrence of NPC. The mechanism underlying remains to be fully elucidated. Aldo-keto reductase B10 (AKR1B10) plays a role in the formation and development of carcinomas. However, its role in resistance to radiotherapy of NPC is not clear. In this research, the relationships between AKR1B10 expression and the treatment effect of NPC patients, NPC cell survival, cell apoptosis, and DNA damage repair, as well as the effect and mechanism of AKR1B10 expression on NPC radioresistance were explored. A total of 58 paraffin tissues of NPC patients received radiotherapy were collected including 30 patients with radiosensitivity and 28 patients with radioresistance. The relationships between AKR1B10 expression and the treatment effect as well as clinical characteristics were analyzed by immuno-histochemical experiments, and the roles of AKR1B10 in cell survival, apoptosis and DNA damage repair were detected using the AKR1B10 overexpressed cell models. Furthermore the mechanism of AKR1B10 in NPC radioresistance was explored. Finally, the radioresistance effect of AKR1B10 expression was evaluated by the tumor xenograft model of nude mice and the method of radiotherapy. The results showed AKR1B10 expression level was correlated with radiotherapy resistance, and AKR1B10 overexpression promoted proliferation of NPC cells, reduced apoptosis and decreased cellular DNA damage after radiotherapy. The probable molecular mechanism is that AKR1B10 expression activated FFA/TLR4/NF-κB axis in NPC cells. This was validated by using the TLR4 inhibitor TAK242 to treat NPC cells with AKR1B10 expression, which reduced the phosphorylation of NF-κB. This study suggests that AKR1B10 can induce radiotherapy resistance and promote cell survival via FFA/TLR4/NF-κB axis in NPC, which may provide a novel target to fight against radiotherapy resistance of NPC.

The midbrain participates in complex neural information processing in the ascending and descending circuits, but their organization remains unclear due to the lack of comprehensive dissection of the characterization of individual neurons. Combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired the whole-brain dataset with high resolution and reconstructed the detailed morphology of the pontine-tegmental cholinergic neurons (PTCNs). As the main cholinergic system of the midbrain, the individual PTCNs own abundant axons with length up to 60 cm and 5000 terminal branches and innervate multiple brain regions from the spinal cord to cortex in both hemispheres. According to various targeting regions in the ascending and descending circuits, individual PTCNs could be grouped into four types and the axonal fibers of cholinergic neurons in the pedunculopontine nucleus present more divergent while neurons in the laterodorsal tegmental nucleus contain richer axonal fibers and dendrites. In the axonal targeting nuclei, such as in the thalamus or cortex, the individual neurons innervate multiple sub-regions with separate pathways. These results provide the detailed organization characterization of the cholinergic neurons to understand the connection logic of the midbrain.

The extreme complexity of mammalian brains requires a comprehensive deconstruction of neuroanatomical structures. Scientists normally use a brain stereotactic atlas to determine the locations of neurons and neuronal circuits. However, different brain images are normally not naturally aligned even when they are imaged with the same setup, let alone under the differing resolutions and dataset sizes used in mesoscopic imaging. As a result, it is difficult to achieve high-throughput automatic registration without manual intervention. Here, we propose a deep learning-based registration method called DeepMapi to predict a deformation field used to register mesoscopic optical images to an atlas. We use a self-feedback strategy to address the problem of imbalanced training sets (sampling at a fixed step size in nonuniform brains of structures and deformations) and use a dual-hierarchical network to capture the large and small deformations. By comparing DeepMapi with other registration methods, we demonstrate its superiority over a set of ground truth images, including both optical and MRI images. DeepMapi achieves fully automatic registration of mesoscopic micro-optical images, even macroscopic MRI datasets, in minutes, with an accuracy comparable to those of manual annotations by anatomists. Electronic supplementary material The online version of this article (10.1007/s12021-020-09483-7) contains supplementary material, which is available to authorized users.

Purpose Colorectal cancer (CRC) is one of the major contributors to cancer mortality and morbidity. Finding strategies to fight against CRC is urgently required. Mutations in driver genes of APC or β-catenin play an important role in the occurrence and progression of CRC. In the present study, we jointly apply CRISPR/Cas9-sgRNA system and Single-stranded oligodeoxynucleotide (ssODN) as templates to correct a heterozygous ΔTCT deletion mutation of β-catenin present in a colon cancer cell line HCT-116. This method provides a potential strategy in gene therapy for cancer. Methods A Cas9/β-catenin-sgRNA-eGFP co-expression vector was constructed and co-transfected with ssODN into HCT-116 cells. Mutation-corrected single-cell clones were sorted by FACS and judged by TA cloning and DNA sequencing. Effects of CRISPR/Cas9-mediated correction were tested by real-time quantitative PCR, Western blotting, CCK8, EDU dyeing and cell-plated clones. Moreover, the growth of cell clones derived tumors was analyzed at nude mice xenografts. Results CRISPR/Cas9-mediated β-catenin mutation correction resulted in the presence of TCT sequence and the re-expression of phosphorylation β-catenin at Ser45, which restored the normal function of phosphorylation β-catenin including reduction of the transportation of nuclear β-catenin and the expression of downstream c-myc, survivin. Significantly reduced cell growth was observed in β-catenin mutation-corrected cells. Mice xenografted with mutation-corrected HCT-116 cells showed significantly smaller tumor size than uncorrected xenografts. Conclusion The data of this study documented that correction of the driven mutation by the combination of CRISPR/Cas9 and ssODN could greatly remedy the biological behavior of the cancer cell line, suggesting a potential application of this strategy in gene therapy of cancer.

The zona incerta (ZI) is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation. However, the long-range connectivity of different sectors in the mouse ZI has not been comprehensively mapped. Here, we obtained whole-brain images of the input and output connections via fluorescence micro-optical sectioning tomography and viral tracing. The principal regions in the input-output circuits of ZI GABAergic neurons were topologically organized. The 3D distribution of cortical inputs showed rostro-caudal correspondence with different ZI sectors, while the projection fibers from ZI sectors were longitudinally organized in the superior colliculus. Clustering results show that the medial and lateral ZI are two different major functional compartments, and they can be further divided into more subdomains based on projection and input connectivity. This study provides a comprehensive anatomical foundation for understanding how the ZI is involved in integrating different information, conveying motivational states, and modulating global behaviors.

Fear of hypoglycemia is a significant concern for parents of children/ adolescents with type 1 diabetes. Although some studies have explained the parental fear of hypoglycemia, the related factors were yet to be determined. This systematic review aims to identify the related factors of fear of hypoglycemia in the parents of children and adolescents with type 1 diabetes and provide a theoretical basis for further intervention.PubMed, MEDLINE, EMBASE, Scopus, CINAHL, EBSCO, Web of Science, and Cochrane Library were systematically searched from 2010 to 2021. Studies evaluating the fear of hypoglycemia of parents and its associated factors were included.Twenty-three observational articles met the criteria.Significant associations were found between fear of hypoglycemia and specific factors, including motherhood, nocturnal hypoglycemia, and the number of blood glucose monitoring. Psychological factors, including anxiety, depression, pediatric parenting stress, mindfulness, self-efficacy, quality of life, and sleep disorders, were conclusive and associations with parental fear of hypoglycemia.Understanding parental fear of hypoglycemia can help parents prevent potential problems in diabetes management, thus promoting children's growth. According to current evidence, effective targeted interventions based on modifiable relevant factors can be developed to reduce the fear of hypoglycemia in parents while maintaining optimal blood glucose control in children/ adolescents.Health professionals should pay more attention to the mental health of parents, and parents should be involved in the care plan and have the opportunity to discuss their fear of hypoglycemia in the most appropriate way to manage type 1 diabetes.