318 research outputs found

    A Research on the Development Path of New Urbanization Based on Low-Carbon Perspective

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    China is in a decisive phase of building a moderately prosperous society, and the steady sequence of urbanization has great significance in promoting economic and social development. While in the process of urbanization, some problems are challenging the development quality of Chinese urbanization and the planning concepts of new urbanization, such as urban industrial pollution, agricultural high carbon emissions, high-carbon lifestyle of urban residents, etc.. Therefore, from low-carbon perspective and with the current status of Chinese urbanization development as the object for the study, the paper introduces the mainly high-carbon emissions in all aspects of the urbanization process in China and proposes a low-carbon ecological path for the sustainable development in the future.China is in a decisive phase of building a moderately prosperous society, and the steady sequence of urbanization has great significance in promoting economic and social development. While in the process of urbanization, some problems are challenging the development quality of Chinese urbanization and the planning concepts of new urbanization, such as urban industrial pollution, agricultural high carbon emissions, high-carbon lifestyle of urban residents, etc.. Therefore, from low-carbon perspective and with the current status of Chinese urbanization development as the object for the study, the paper introduces the mainly high-carbon emissions in all aspects of the urbanization process in China and proposes a low-carbon ecological path for the sustainable development in the future

    Genome-Wide Association Study and Transcriptome Differential Expression Analysis of the Feather Rate in Shouguang Chickens

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    The feather rate phenotype in chicks, including early-feathering and late-feathering phenotypes, are widely used as a sexing system in the poultry industry. The objective of this study was to obtain candidate genes associated with the feather rate in Shouguang chickens. In the present study, we collected 56 blood samples and 12 hair follicle samples of flight feathers from female Shouguang chickens. Then we identified the chromosome region associated with the feather rate by genome-wide association analysis (GWAS). We also performed RNA sequencing and analyzed differentially expressed genes between the early-feathering and late-feathering phenotypes using HISAT2, StringTie, and DESeq2. We identified a genomic region of 10.0–13.0 Mb of chromosome Z, which is statistically associated with the feather rate of Shouguang chickens at one-day old. After RNA sequencing analysis, 342 differentially expressed known genes between the early-feathering (EF) and late-feathering (LF) phenotypes were screened out, which were involved in epithelial cell differentiation, intermediate filament organization, protein serine kinase activity, peptidyl-serine phosphorylation, retinoic acid binding, and so on. The sperm flagellar 2 gene (SPEF2) and prolactin receptor (PRLR) gene were the only two overlapping genes between the results of GWAS and differential expression analysis, which implies that SPEF2 and PRLR are possible candidate genes for the formation of the chicken feathering phenotype in the present study. Our findings help to elucidate the molecular mechanism of the feather rate in chicks.</p

    Microglia Prevent Beta-Amyloid Plaque Formation in the Early Stage of an Alzheimer\u27s Disease Mouse Model with Suppression of Glymphatic Clearance

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    BACKGROUND: Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer\u27s disease (AD) are currently unknown. METHODS: Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4−/−) mice, and AQP4−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein E (apoE) expression, on Aβ burden, was also investigated in the frontal cortex of AQP4−/−/APP/PS1 mice and APP/PS1 mice. RESULTS: AQP4 deletion in APP/PS1 mice significantly exaggerated glymphatic clearance dysfunction, and intraneuronal accumulation of Aβ and apoE, although it did not lead to Aβ plaque deposition. Notably, microglia, but not astrocytes, increased activation and phagocytosis of Aβ in the cerebral cortex of AQP4−/−/APP/PS1 mice, compared with APP/PS1 mice. Selectively eliminating microglia in the frontal cortex via local injection of clodronate liposomes resulted in deposition of Aβ plaques in AQP4−/−/APP/PS1 mice, but not APP/PS1 mice. Moreover, knockdown of apoE reduced intraneuronal Aβ levels in both APP/PS1 mice and AQP4−/−/APP/PS1 mice, indicating an inhibitory effect of apoE on Aβ clearance. CONCLUSION: The above results suggest that the glymphatic system mediated Aβ and apoE clearance and microglia mediated Aβ degradation synergistically prevent Aβ plague formation in the early stages of the AD mouse model. Protecting one or both of them might be beneficial to delaying the onset of AD

    Generation of Monoclonal Antibodies against Highly Conserved Antigens

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    Background: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. Methodology/Principal Findings: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1) and one mouse self-antigen (TNF-alpha) as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. Conclusions/Significance: We developed an efficient and universal method for generating surrogate or therapeuti

    Deletion of Aquaporin-4 in APP/PS1 Mice Exacerbates Brain Aβ Accumulation and Memory Deficits

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    BACKGROUND: Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer\u27s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent. RESULTS: Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignificant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples. CONCLUSIONS: These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD

    HuatuoGPT, towards Taming Language Model to Be a Doctor

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    In this paper, we present HuatuoGPT, a large language model (LLM) for medical consultation. The core recipe of HuatuoGPT is to leverage both \textit{distilled data from ChatGPT} and \textit{real-world data from doctors} in the supervised fine-tuned stage. The responses of ChatGPT are usually detailed, well-presented and informative while it cannot perform like a doctor in many aspects, e.g. for integrative diagnosis. We argue that real-world data from doctors would be complementary to distilled data in the sense the former could tame a distilled language model to perform like doctors. To better leverage the strengths of both data, we train a reward model to align the language model with the merits that both data bring, following an RLAIF (reinforced learning from AI feedback) fashion. To evaluate and benchmark the models, we propose a comprehensive evaluation scheme (including automatic and manual metrics). Experimental results demonstrate that HuatuoGPT achieves state-of-the-art results in performing medical consultation among open-source LLMs in GPT-4 evaluation, human evaluation, and medical benchmark datasets. It is worth noting that by using additional real-world data and RLAIF, the distilled language model (i.e., HuatuoGPT) outperforms its teacher model ChatGPT in most cases. Our code, data, and models are publicly available at \url{https://github.com/FreedomIntelligence/HuatuoGPT}. The online demo is available at \url{https://www.HuatuoGPT.cn/}

    Age-Related Alterations in Electroencephalography Connectivity and Network Topology During n-Back Working Memory Task

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    The study of the healthy brain in elders, especially age-associated alterations in cognition, is important to understand the deficits created by Alzheimer's disease (AD), which imposes a tremendous burden on individuals, families, and society. Although, the changes in synaptic connectivity and reorganization of brain networks that accompany aging are gradually becoming understood, little is known about how normal aging affects brain inter-regional synchronization and functional networks when items are held in working memory (WM). According to the classic Sternberg WM paradigm, we recorded multichannel electroencephalography (EEG) from healthy adults (young and senior) in three different conditions, i.e., the resting state, 0-back (control) task, and 2-back task. The phase lag index (PLI) between EEG channels was computed and then weighted and undirected network was constructed based on the PLI matrix. The effects of aging on network topology were examined using a brain connectivity toolbox. The results showed that age-related alteration was more prominent when the 2-back task was engaged, especially in the theta band. For the younger adults, the WM task evoked a significant increase in the clustering coefficient of the beta-band functional connectivity network, which was absent in the older adults. Furthermore, significant correlations were observed between the behavioral performance of WM and EEG metrics in the theta and gamma bands, suggesting the potential use of those measures as biomarkers for the evaluation of cognitive training, for instance. Taken together, our findings shed further light on the underlying mechanism of WM in physiological aging and suggest that different EEG frequencies appear to have distinct functional correlates in cognitive aging. Analysis of inter-regional synchronization and topological characteristics based on graph theory is thus an appropriate way to explore natural age-related changes in the human brain
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