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"Gu, Jing-Jing"
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Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases
Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.
Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. Here the authors employ scRNA-seq to explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases.
Journal Article
China's Private Enterprises in Africa and the Implications for African Development
This paper evaluates the growing presence of China's private business sector in Africa. Currently, attention focuses on China's state-owned enterprises in extractive industries. Less attention is paid to Chinese private enterprises. This study fills a knowledge-gap by evaluating characteristics and motivations of Chinese private firms in Africa, and assesses their development impacts. Key findings are that the Chinese private firms have followed their own paths to Africa, and the primary factors driving private investment are African market opportunities, competition within China and the presence of a strong entrepreneurial spirit. An effective mechanism bridging a gap between China's African Policy and its implementation in terms of private sector engagement is lacking. To maximise development gains, a top-down and bottom-up ‘two-way street’ approach to Chinese public–private sector relations is necessary. This is a mutual learning process for the Chinese public and private sectors and also China–Africa relations. These are fluid relationships with each adapting to and shaping the other.
Journal Article
Dynamic evolution and reversibility of single-atom Ni(II) active site in 1T-MoS2 electrocatalysts for hydrogen evolution
1T-MoS
2
and single-atom modified analogues represent a highly promising class of low-cost catalysts for hydrogen evolution reaction (HER). However, the role of single atoms, either as active species or promoters, remains vague despite its essentiality toward more efficient HER. In this work, we report the unambiguous identification of Ni single atom as key active sites in the basal plane of 1T-MoS
2
(Ni@1T-MoS
2
) that result in efficient HER performance. The intermediate structure of this Ni active site under catalytic conditions was captured by in situ X-ray absorption spectroscopy, where a reversible metallic Ni species (Ni
0
) is observed in alkaline conditions whereas Ni remains in its local structure under acidic conditions. These insights provide crucial mechanistic understanding of Ni@1T-MoS
2
HER electrocatalysts and suggest that the understanding gained from such in situ studies is necessary toward the development of highly efficient single-atom decorated 1T-MoS
2
electrocatalysts.
While single atom catalysis combines heterogeneous materials with molecular understanding, the role of the single atoms remains vague. Here, authors examine single Ni on MoS
2
via in situ X-ray absorption spectroscopy to reveal the intermediate and catalytically active species.
Journal Article
Global health effects of future atmospheric mercury emissions
Mercury is a potent neurotoxin that poses health risks to the global population. Anthropogenic mercury emissions to the atmosphere are projected to decrease in the future due to enhanced policy efforts such as the Minamata Convention, a legally-binding international treaty entered into force in 2017. Here, we report the development of a comprehensive climate-atmosphere-land-ocean-ecosystem and exposure-risk model framework for mercury and its application to project the health effects of future atmospheric emissions. Our results show that the accumulated health effects associated with mercury exposure during 2010–2050 are $19 (95% confidence interval: 4.7–54) trillion (2020 USD) realized to 2050 (3% discount rate) for the current policy scenario. Our results suggest a substantial increase in global human health cost if emission reduction actions are delayed. This comprehensive modeling approach provides a much-needed tool to help parties to evaluate the effectiveness of Hg emission controls as required by the Minamata Convention.
Mercury is a neurotoxin and pollutant with enhanced emissions from anthropogenic activities. Here, the authors develop a global emissions, transport, and human risk model and find substantial future losses in revenue and public health if emission reductions proposed by the Minamata Convention are delayed.
Journal Article
Atomically engineering activation sites onto metallic 1T-MoS2 catalysts for enhanced electrochemical hydrogen evolution
Engineering catalytic sites at the atomic level provides an opportunity to understand the catalyst’s active sites, which is vital to the development of improved catalysts. Here we show a reliable and tunable polyoxometalate template-based synthetic strategy to atomically engineer metal doping sites onto metallic 1T-MoS
2
, using Anderson-type polyoxometalates as precursors. Benefiting from engineering nickel and oxygen atoms, the optimized electrocatalyst shows great enhancement in the hydrogen evolution reaction with a positive onset potential of ~ 0 V and a low overpotential of −46 mV in alkaline electrolyte, comparable to platinum-based catalysts. First-principles calculations reveal co-doping nickel and oxygen into 1T-MoS
2
assists the process of water dissociation and hydrogen generation from their intermediate states. This research will expand on the ability to improve the activities of various catalysts by precisely engineering atomic activation sites to achieve significant electronic modulations and improve atomic utilization efficiencies.
While heterogeneous catalysts can act as tangible, efficient materials for energy conversion, understanding the active catalytic sites is challenging. Here, authors engineer specific catalytic sites into molybdenum sulfide to improve and elucidate hydrogen evolution electrocatalysis.
Journal Article
Systematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer’s disease
BackgroundAlzheimer’s disease (AD) is the leading cause of dementia. Currently, there are no effective disease-modifying treatments for AD. Mendelian randomisation (MR) has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for AD and analyse their pathophysiological mechanisms and potential side effects.MethodsA two-sample MR integrating the identified druggable genes was performed to estimate the causal effects of blood and brain druggable expression quantitative trait loci (eQTLs) on AD. A repeat study was conducted using different blood and brain eQTL data sources to validate the identified genes. Using AD markers with available genome-wide association studies data, we evaluated the causal relationship between established AD markers to explore possible mechanisms. Finally, the potential side effects of the druggable genes for AD treatment were assessed using a phenome-wide MR.ResultsOverall, 5883 unique druggable genes were aggregated; 33 unique potential druggable genes for AD were identified in at least one dataset (brain or blood), and 5 were validated in a different dataset. Among them, three prior druggable genes (epoxide hydrolase 2 (EPHX2), SERPINB1 and SIGLEC11) reached significant levels in both blood and brain tissues. EPHX2 may mediate the pathogenesis of AD by affecting the entire hippocampal volume. Further phenome-wide MR analysis revealed no potential side effects of treatments targeting EPHX2, SERPINB1 or SIGLEC11.ConclusionsThis study provides genetic evidence supporting the potential therapeutic benefits of targeting the three druggable genes for AD treatment, which will be useful for prioritising AD drug development.
Journal Article
Infertility-related stress is associated with quality of life through negative emotions among infertile outpatients
Infertility is not a fatal disease but it really produces infertility-related stress and affects individuals’ quality of life to a great extent. This study aims to investigate the relations among infertility-related stress, negative emotions and quality of life in infertile outpatients, and suppose gender difference as well as Dark Triad, which contained three dark personality traits: Machiavellianism, narcissism, and psychopathy, would moderate the relations. 105 infertile outpatients age range 20–49 completed a cross-sectional questionnaire on the Fertility Quality of Life scale, the Fertility Problem Inventory, the Hospital Anxiety and Depression Scale a the Chinese version of Dirty Dozen. Results showed that negative emotions mediated the relations between infertility-related stress and quality of life. Dark Triad could not moderate the relations between infertility-related stress, negative emotions, and quality of life, but gender can moderate the associations between infertility-related stress and negative emotions. Specifically, the association between infertility-related stress and negative emotions was stronger in men than in women. Infertility-related stress has direct and indirect effects on infertile outpatients’ quality of life. It is important to consider the important roles of emotions and gender difference between patients, and delivering targeted intervention programs.
Journal Article
Thioredoxin-interacting protein regulates insulin transcription through microRNA-204
Thioredoxin-interacting protein (TXNIP) regulates the redox potential of cells and has previously been found to be upregulated in diabetic states. In a new study, Anath Shalev and colleagues show that TXNIP upregulates the expression of miR-204, which in turn downregulates the expression of MAFA, a key transcription factor regulating insulin expression. These results could further explain the progression of diabetes.
Beta-cell dysfunction and impaired insulin production are hallmarks of diabetes
1
, but despite the growing diabetes epidemic, the molecular mechanisms underlying this disease have remained unclear. We identified thioredoxin-interacting protein (TXNIP), a cellular redox regulator, as a crucial factor in beta-cell biology and show that beta-cell TXNIP is upregulated in diabetes, whereas TXNIP deficiency protects against diabetes by preventing beta-cell apoptosis
2
,
3
. Here we show that TXNIP and diabetes induce beta-cell expression of a specific microRNA, miR-204, which in turn blocks insulin production by directly targeting and downregulating
MAFA
, a known insulin transcription factor. In particular, we first discovered the regulation of miR-204 by TXNIP by microarray analysis, followed by validation studies in INS-1 beta cells, islets of Txnip-deficient mice, diabetic mouse models and primary human islets. We then further found that TXNIP induces miR-204 by inhibiting the activity of signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in miR-204 regulation
4
,
5
. We also identified
MAFA
as a target that is downregulated by miR-204. Taken together, our results demonstrate that TXNIP controls microRNA expression and insulin production and that miR-204 is involved in beta-cell function. The newly identified TXNIP–miR-204–MAFA–insulin pathway may contribute to diabetes progression and provides new insight into TXNIP function and microRNA biology in health and disease.
Journal Article