Direct reprogramming of induced neural progenitors: a new promising strategy for AD treatment.

Alzheimer\u27s disease (AD) is a prominent form of dementia, characterized by aggregation of the amyloid β-peptide (Aβ) plaques and neurofibrillary tangles, loss of synapses and neurons, and degeneration of cognitive functions. Currently, although a variety of medications can relieve some of the symptoms, there is no cure for AD. Recent breakthroughs in the stem cell field provide promising strategies for AD treatment. Stem cells including embryonic stem cells (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) are potentials for AD treatment. However, the limitation of cell sources, safety issues, and ethical issues restrict their applications in AD. Recently, the direct reprogramming of induced neural progenitor cells (iNPCs) has shed light on the treatment of AD. In this review, we will discuss the latest progress, challenges, and potential applications of direct reprogramming in AD treatment

AIO-P: Expanding Neural Performance Predictors Beyond Image Classification

Evaluating neural network performance is critical to deep neural network design but a costly procedure. Neural predictors provide an efficient solution by treating architectures as samples and learning to estimate their performance on a given task. However, existing predictors are task-dependent, predominantly estimating neural network performance on image classification benchmarks. They are also search-space dependent; each predictor is designed to make predictions for a specific architecture search space with predefined topologies and set of operations. In this paper, we propose a novel All-in-One Predictor (AIO-P), which aims to pretrain neural predictors on architecture examples from multiple, separate computer vision (CV) task domains and multiple architecture spaces, and then transfer to unseen downstream CV tasks or neural architectures. We describe our proposed techniques for general graph representation, efficient predictor pretraining and knowledge infusion techniques, as well as methods to transfer to downstream tasks/spaces. Extensive experimental results show that AIO-P can achieve Mean Absolute Error (MAE) and Spearman's Rank Correlation (SRCC) below 1% and above 0.5, respectively, on a breadth of target downstream CV tasks with or without fine-tuning, outperforming a number of baselines. Moreover, AIO-P can directly transfer to new architectures not seen during training, accurately rank them and serve as an effective performance estimator when paired with an algorithm designed to preserve performance while reducing FLOPs.Comment: AAAI 2023 Oral Presentation; version includes supplementary material; 16 Pages, 4 Figures, 22 Table

Effect of tea polyphenols on intestinal barrier and immune function in weaned lambs

IntroductionThe purpose of this study was to explore the effects of tea polyphenols on growth performance, cytokine content, intestinal antioxidant status and intestinal barrier function of lambs, in order to provide reference for intestinal health of ruminants.MethodsThirty weaned lambs (average initial weight 9.32 ± 1.72 kg) were randomly divided into five groups with six lambs in each group. The control group did not add anything but the basic diet mainly composed of Pennisetum and Corn, and the other four groups added 2, 4, 6 g/kg tea polyphenols and 50 mg/kg chlortetracycline to the basic diet, respectively. The experiment lasted for 42 days.ResultsDietary tea polyphenols improved the growth and stress response and reduced intestinal permeability of lambs (p > 0.05), while CTC did not affect the final lamb weight (p > 0.05). Both tea phenols and CTC significantly reduced inflammatory factors and enhanced the immune system (p > 0.05). Dietary tea polyphenols increased villus height, villus height/crypt depth, secretory immunoglobulin A (p > 0.05), and antioxidant enzymes, while decreasing MDA and apoptosis in the intestine (p > 0.05). However, compared with other groups, the content of T-AOC in jejunum did not change significantly (p > 0.05). Tea polyphenols also increased claudin-1 levels in the duodenum, jejunum, and ileum more than CTC (p > 0.05). CTC had a limited effect on the mRNA expression of Occludin and ZO-1, while tea polyphenols increased these in both the duodenum and ileum (p > 0.05).ConclusionThis study demonstrated that tea polyphenols can effectively improve the intestinal barrier of weaned lambs, and that they have anti-inflammatory and antioxidant effects similar to those of antibiotics. Thus, tea polyphenols could be used to replace antibiotics in ensuring safety of livestock products and in achieving the sustainable development of modern animal husbandry

Folic acid and zinc improve hyperuricemia by altering the gut microbiota of rats with high-purine diet-induced hyperuricemia

A high-purine diet can cause hyperuricemia and destroy the microbial composition of the gut microbiota. Both folic acid and zinc significantly reduce uric acid levels and alleviate hyperuricemia. However, whether the underlying mechanisms are associated with the regulation of the gut microbiota remain unknown. To explore alterations of the gut microbiota related to folic acid and zinc treatment in rats with hyperuricemia in our study. A hyperuricemic rat model was established with a high-purine diet. The effects of folic acid and zinc on uric acid levels were evaluated. Alterations of the gut microbiota related to hyperuricemia and the treatments were evaluated by sequencing using the Illumina MiSeq system. The results demonstrated that uric acid levels dropped observably, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) were downregulated after folic acid or zinc intervention. 16S rRNA gene sequencing-based gut microbiota analysis revealed that folic acid and zinc enhanced the abundance of probiotic bacteria and reduced that of pathogenic bacteria, thus improving intestinal barrier function. PICRUST analysis indicated that folic acid and zinc restored gut microbiota metabolism. These findings indicate that folic acid and zinc ameliorate hyperuricemia by inhibiting uric acid biosynthesis and stimulating uric acid excretion by modulating the gut microbiota. Thus, folic acid and zinc may be new and safe therapeutic agents to improve hyperuricemia

CD146+ mural cells from infantile hemangioma display proangiogenic ability and adipogenesis potential in vitro and in xenograft models

ObjectiveInfantile hemangioma (IH), the most common infantile vascular neoplasm, is uniquely characterized by rapid proliferation followed by slow spontaneous involution lasting for years. In IH lesions, perivascular cells are the most dynamic cell subset during the transition from the proliferation phase to the involution phase, and we aimed to systematically study this kind of cell.Methods and resultsCD146-selective microbeads were used to isolate IH-derived mural-like cells (HemMCs). Mesenchymal markers of HemMCs were detected by flow cytometry, and the multilineage differentiation potential of HemMCs was detected by specific staining after conditioned culture. CD146-selected nonendothelial cells from IH samples showed characteristics of mesenchymal stem cells with distinct angiogenesis-promoting effects detected by transcriptome sequencing. HemMCs spontaneously differentiated into adipocytes 2 weeks after implantation into immunodeficient mice, and almost all HemMCs had differentiated into adipocytes within 4 weeks. HemMCs could not be induced to differentiate into endothelial cells in vitro. However, 2 weeks after implantation in vivo, HemMCs in combination with human umbilical vein endothelial cells (HUVECs) formed GLUT1+ IH-like blood vessels, which spontaneously involuted into adipose tissue 4 weeks after implantation.ConclusionsIn conclusion, we identified a specific cell subset that not only showed behavior consistent with the evolution of IH but also recapitulated the unique course of IH. Thus, we speculate that proangiogenic HemMCs may be a potential target for the construction of hemangioma animal models and the study of IH pathogenesis

Highly-stable P2-Na 0.67 MnO 2 electrode enabled by lattice tailoring and surface engineering

Abstract(#br)One of the key challenges of sodium ion batteries is to develop sustainable, low-cost and high capacity cathodes, and this is the reason that layered sodium manganese oxides have attracted so much attention. However, the undesired phase transitions and poor electrolyte-electrode interfacial stability facilitate their capacity decay and limit their practical applications. Herein, we design a novel Al 2 O 3 @Na 0.67 Zn 0.1 Mn 0.9 O 2 electrode to mitigate these problems, by taking the advantages of both structural stabilization and surface passivation via Zn 2+ substitution and Al 2 O 3 atomic layered deposition (ALD), respectively. Long-range and local structural analyses during charging/discharging processes indicate that P2-P2’ phase transformation can be suppressed by substituting proper amount of Mn 3+ Jahn-Teller centers with Zn 2+ , whereas excessive Zn 2+ leads to P2-OP4 structure transition at low sodium contents and facilitates the electrode degradations. Furthermore, the homogeneous and robust cathode electrolyte interphase (CEI) layers formed on the Al 2 O 3 -coated electrodes effectively hinder the organic electrolytes from further decomposition. Therefore, our synergetic strategy of Zn 2+ substitution and ALD surface engineering remarkably boosts the cycling performance of P2-Na 0.67 MnO 2 and provides some new insights into the designing of highly stable cathode electrodes for sustainable sodium ion batteries

A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: The ANU-ADRI

Background and Aims: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts. Methods: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age ≥53 years), the Kungsholmen Project (KP) (n = 905, age ≥75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age ≥65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index. Results: For the ANU-ADRI using available data, the MAP study c-statistic was 0.637 (95% CI 0.596-0.678), for the KP study it was 0.740 (0.712-0.768) and for the CVHS it was 0.733 (0.691-0.776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625). Conclusion: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up. © 2014 Anstey et al

Thermodynamic Interactions in Polydiene/Polyolefin Blends

Thermodynamic interactions in blends of polydienes and polyolefins were investigated using small angle neutron scattering (SANS). Model polydienes with controlled molecular weight, dispersity, and precise chemical structure were synthesized using anionic polymerization, and subsequently saturated with hydrogen or deuterium to form model polyolefins. The polydienes involved in this study include a series polybutadienes (PBD) with varying amounts of 1,2 and 1,4 microstructure units and 1,4-polyisoprene (1,4-PI); the corresponding polyolefins included are poly(ethyl ethylene) (PEE), polyethylene (PE), PE-co-PEE random copolymers, and poly(ethylene-alt-propylene) (PEP). Additionally, a model atactic polypropylene (aPP) prepared using a metallocene catalyst was used in this study. SANS data were interpreted using Zimm analysis and the Random Phase Approximation model to extract the Flory-Huggins interaction parameter, and chain dimensions of the pure components. The thermodynamic interactions in blends of polydienes and polyolefins were demonstrated to be repulsive, quantitatively large, and strongly temperature dependent. The chain dimensions of the components were mostly expanded compared to literature values. Interactions in blends of polydienes and polyolefins were uncorrelated to the statistical segment length disparity between the components. Predictions of the interaction parameters from pure component PVT properties were found to qualitatively describe the relative trends of the measured interaction parameters, with some exceptions, but failed to capture the magnitude of the interaction parameters. The Lattice Cluster Theory (LCT) also did not describe the absolute values of interaction parameters, proposed to originate from non-random mixing effects in the enthalpic contribution to the interaction parameters, which are not included in the theory. Blends were also examined containing random copolymers of polydienes and polyolefins, in order to modulate the large polydiene/polyolefin interaction parameters. The random copolymer theory (RCT) quantitatively predicted interaction parameters for some of the polydiene/polyolefin blends, including 1,2-PBD-co-PEE/PEE blends, 1,4-PI-co-PEP/PEP blends, and 1,2-PBD-co-PEE/1,4-PI blends, which indicates the interactions were dominated by dispersive forces. Sequence effects were also unimportant for the model polydiene-polyolefin copolymers employed in this study. We observed that RCT failed in some systems which contain complex random copolymer repeat units such as multiple olefinic repeat units in PE-co-PEE/1,4-PI blends. The existing theories were unable to explain the departure from RCT, and modified theories need to be developed.Chemical and Biomolecular Engineering, Department o

Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy

Fabrication of artificial nacre-like hexagonal boron nitride/lignocellulosic fiber composites with high thermal conductivity

The low thermal expansion coefficient, low dielectric constant, high thermal conductivity, high electrical resistivity, and excellent thermal stability of hexagonal boron nitride (hBN) make it an ideal filler for insulating and thermally conductive composite films. Its use has been suggested in insulating packaging systems to solve the heat dissipation problems in modern electronic equipment. Here, a novel strategy was proposed to construct superior thermally conductive networks via the vacuum-assisted filtration of hydroxyl-modified hexagonal boron nitride (BN-OH) and lignocellulosic fiber (LCF). The π–π interactions between the benzene ring of LCF and the hBN plane assist in the dispersal of BN-OH in aqueous solution. The abundance of functional groups such as hydroxyl and phenolic hydroxyl groups in the LCF structure allow for hydrogen bonding with the hydroxyl groups on the BN-OH surface, increasing interfacial interactions between BN-OH and LCF and reducing interfacial thermal resistance. In addition, the long-range one-dimensional structure of LCF can assist in the formation of a self-supporting, high-thermal-conductivity film with a high content of BN-OH. The through-plane thermal conductivity of BN-OH/LCF reached 5.34 W/(m⋅K) at 90 wt.% BN loading. This work provides inspiration for the green preparation of hBN thermally conductive composite films with high filler loadings