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"Chen, Zheng"
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AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial
Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.
This single-arm, single-centre trial enrolled children (aged 1–18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing.
Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1–2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40–57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5–4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery.
AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9.
National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.
Journal Article
Sport policy in China
\"Acknowledging China's established status as a global sporting superpower, this is the first book to systematically investigate sport policy in that country. With a focus on sport development in the most recent three decades, Sport Policy in China explores a wide range of topics in Chinese sport, including elite sport development, professional sports, major sports events, sport for all, the political context within which sport is interiorised and the distinctive sporting status of Hong Kong. It examines the debates around policy, globalisation, diplomacy and soft power, as well as the significance of the principle of 'one country, two systems'. With international appeal, this book is a valuable resource for students and researchers in the fields of sport policy, sport management, sport development and sport sociology\"-- Provided by publisher.
Book
Regulating the coordination structure of single-atom Fe-NxCy catalytic sites for benzene oxidation
Atomically dispersed metal-N-C structures are efficient active sites for catalyzing benzene oxidation reaction (BOR). However, the roles of N and C atoms are still unclear. We report a polymerization-regulated pyrolysis strategy for synthesizing single-atom Fe-based catalysts, and present a systematic study on the coordination effect of Fe-N
x
C
y
catalytic sites in BOR. The special coordination environment of single-atom Fe sites brings a surprising discovery: Fe atoms anchored by four-coordinating N atoms exhibit the highest BOR performance with benzene conversion of 78.4% and phenol selectivity of 100%. Upon replacing coordinated N atoms by one or two C atoms, the BOR activities decrease gradually. Theoretical calculations demonstrate the coordination pattern influences not only the structure and electronic features, but also the catalytic reaction pathway and the formation of key oxidative species. The increase of Fe-N coordination number facilitates the generation and activation of the crucial intermediate O=Fe=O species, thereby enhancing the BOR activity.
Atomically dispersed metal-N-C are efficient active site for benzene oxidation but the roles of N and C atoms are still unclear. Here the authors report a highly-active single-atom Fe-based benzene oxidation catalyst and provide deep insights into the structure-activity relationship at atomic level.
Journal Article
21st century Maritime Silk Road : a peaceful way forward
\"This book focuses on understanding the characteristics of the marine environment; overall characteristic of the marine resources (especially the marine new energy) and their current utilization; important routes, channels, and ports; and the Maritime Silk Road from the perspective of international law. It also discusses the significance and opportunities of the Maritime Silk Road initiative, analyzes the challenges involved in the construction of the Maritime Silk Road and provides corresponding countermeasures. Based on the above research, this book also proposes to construct a comprehensive application platform for the Maritime Silk Road that will be a practical tool for decision-making. This book is one of the series publications on the 21st century Maritime Silk Road (shortened as \"Maritime Silk Road\"). This series publications cover the characteristics of the marine environment and marine new energy, remote islands and reefs construction, climate change, early warning of wave disasters, legal escort, marine environment and energy big data construction, etc. contributing to the safe and efficient construction of the Maritime Silk Road. It aims to improve our knowledge of the ocean, thus to improve the capacity for marine construction, enhance the viability of remote islands and reefs, ease the energy crisis and protect the ecological environment, improve the quality of life of residents along the Maritime Silk Road, and protect the rights, interests of the countries and regions participating in the construction of the Maritime Silk Road. It will be a valuable reference for decision-makers, researchers, and marine engineers working in the related fields.\"-- Provided by publisher.
Book
Iridium single-atom catalyst on nitrogen-doped carbon for formic acid oxidation synthesized using a general host–guest strategy
Single-atom catalysts not only maximize metal atom efficiency, they also display properties that are considerably different to their more conventional nanoparticle equivalents, making them a promising family of materials to investigate. Herein we developed a general host–guest strategy to fabricate various metal single-atom catalysts on nitrogen-doped carbon (M1/CN, M = Pt, Ir, Pd, Ru, Mo, Ga, Cu, Ni, Mn). The iridium variant Ir1/CN electrocatalyses the formic acid oxidation reaction with a mass activity of 12.9 AmgIr−1 whereas an Ir/C nanoparticle catalyst is almost inert (~4.8 × 10−3 AmgIr−1). The activity of Ir1/CN is also 16 and 19 times greater than those of Pd/C and Pt/C, respectively. Furthermore, Ir1/CN displays high tolerance to CO poisoning. First-principle density functional theory reveals that the properties of Ir1/CN stem from the spatial isolation of iridium sites and from the modified electronic structure of iridium with respect to a conventional nanoparticle catalyst.Single-atom catalysts maximize metal atom efficiency and exhibit properties that can be considerably different to their nanoparticle equivalent. Now a general host–guest strategy to make various single-atom catalysts on nitrogen-doped carbon has been developed; the iridium variant electrocatalyses the formic acid oxidation reaction with high mass activity and displays high tolerance to CO poisoning.
Journal Article
Poets of the Chinese revolution : Chen Duxiu, Zheng Chaolin, Chen Yi, Mao Zedong
\"How poetry and revolution meshed in Red China. This is a book of poems by four veteran Chinese revolutionaries. Chen Duxiu led China's early cultural awakening before founding the Communist Party in 1921. Mao led the Party to power in 1949. Zheng Chaolin, Chen Duxiu's disciple and, like him, a convert to Trotskyism, spent 34 years in jail, first under the Nationalists and then under Mao. The guerrilla Chen Yi wrote poems in mountain bivouacs or the heat of battle. All wrote in the classical style, which Mao Zedong officially proscribed, though he and other leaders kept using it. Poetry, especially classical poetry, plays a different role in China, and in Chinese revolution, from in the West - it is collective and collaborative. The four poets were entangled with one another in various ways. Chen Duxiu inspired Mao, though Mao later denounced him. Mao and Zheng joined the leadership under Chen Duxiu in the 1920s, though Mao later gaoled Zheng. The maverick Chen Yi was Zheng's associate in France and Mao's comrade-in-arms in China, but he clashed with the Maoists in the Cultural Revolution. Together, the four poets illustrate the complex relationship between Communist revolution and Chinese cultural tradition\"-- Provided by publisher.
BOOK
Dynamic evolution of the active center driven by hemilabile coordination in Cu/CeO2 single-atom catalyst
Hemilability is an important concept in homogeneous catalysis where both the reactant activation and the product formation can occur simultaneously through a reversible opening and closing of the metal-ligand coordination sphere. However, this effect has rarely been discussed in heterogeneous catalysis. Here, by employing a theoretical study on CO oxidation over substituted Cu
1
/CeO
2
single atom catalysts, we show that dynamic evolution of metal-support coordination can significantly change the electronic structure of the active center. The evolution of the active center is shown to either strengthen or weaken the metal-adsorbate bonding as the reaction proceeds from reactants, through intermediates, to products. As a result, the activity of the catalyst can be increased. We explain our observations by extending hemilability effects to single atom heterogenous catalysts and anticipate that introducing this concept can offer a new insight into the important role active site dynamics have in catalysis toward the rational design of more sophisticated single atom catalyst materials.
This work explores the concept of hemilability in single atom catalysts. The results imply that this effect can promote reactant activation and product desorption simultaneously to provide a potential approach to circumvent the Sabatier volcano.
Journal Article
Copper atom-pair catalyst anchored on alloy nanowires for selective and efficient electrochemical reduction of CO2
The electrochemical reduction of CO
2
could play an important role in addressing climate-change issues and global energy demands as part of a carbon-neutral energy cycle. Single-atom catalysts can display outstanding electrocatalytic performance; however, given their single-site nature they are usually only amenable to reactions that involve single molecules. For processes that involve multiple molecules, improved catalytic properties could be achieved through the development of atomically dispersed catalysts with higher complexities. Here we report a catalyst that features two adjacent copper atoms, which we call an ‘atom-pair catalyst’, that work together to carry out the critical bimolecular step in CO
2
reduction. The atom-pair catalyst features stable Cu
1
0
–Cu
1
x
+
pair structures, with Cu
1
x
+
adsorbing H
2
O and the neighbouring Cu
1
0
adsorbing CO
2
, which thereby promotes CO
2
activation. This results in a Faradaic efficiency for CO generation above 92%, with the competing hydrogen evolution reaction almost completely suppressed. Experimental characterization and density functional theory revealed that the adsorption configuration reduces the activation energy, which generates high selectivity, activity and stability under relatively low potentials.
Anchored single-atom catalysts have recently been shown to be very active for various processes, however, a catalyst that features two adjacent copper atoms—which we call an atom-pair catalyst—is now reported. The Cu
1
0
–Cu
1
x
+
pair structures work together to carry out the critical bimolecular step in CO
2
reduction.
Journal Article
NKG2A is a NK cell exhaustion checkpoint for HCV persistence
Exhaustion of cytotoxic effector natural killer (NK) and CD8
+
T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O
Tg
mice permissive for persistent HCV infection, that NK and CD8
+
T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8
+
T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8
+
T cell functions to prevent persistent HCV infection.
Immune cells may become less responsive, or ‘exhausted’, upon chronic viral infection, but the underlying mechanism and crosstalk are still unclear. Here the authors show that, upon chronic hepatitis C virus (HCV) infection, natural killer cell exhaustion is induced by NKG2A signalling to instruct downstream exhaustion of CD8
+
T cells and HCV persistence.
Journal Article