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Electrocatalysis, as a typical heterogeneous catalysis, generally occurs in the di- or tri-phase interfaces. Wettability is an important property for describing the balance of a gas-liquid-solid system. Therefore, the wettability of reaction interface, especially hydrophilicity/hydrophobicity, plays an important role in the adsorption/desorption process of gas bubbles on the surface of the solid electrode. Herein, we present a comprehensive review of the wettability control of the electrode materials applied in electrocatalysis reactions, including hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR) and carbon dioxide reduction reaction (CO2RR). Firstly, the basic theories of wettability as well as the impact on electrocatalysis were introduced in this review. Secondly, the overview of modifying methods of the wettability from electrocatalyst microstructure (structural modification, surface coating, introducing hydrophilic groups) and system design (electrode, device) were suggested. At last, the deficiencies and problems in the application of wettability control are discussed, and deeper and broader application prospects are proposed.

Stability and antipoisoning effects are the main challenges for the application of commercial Pt/C catalysts. Herein, we soaked and adsorbed polydopamine to coat Pt particles on commercial Pt/C and subsequently converted the coatings to few-layer N-doped graphene by calcination to produce Pt/C@NC. The coatings effectively block the direct contact of Pt nanoparticles and electrolyte, thus enhancing the catalyst stability by avoiding Ostwald ripening and suppressing the competitive adsorption of toxicants, contributing to the enhancement of the antipoisoning ability. More importantly, the coatings do not hurt the oxygen reduction reaction (ORR) activity of commercial Pt/C, which exhibits a half wave potential of 0.84 V in an acidic electrolyte. The spectroscopic and theoretical results confirmed that the coatings originate from a strong Pt bonding to pyridinic N of N-doped graphene and that the high ORR activity results from the coordinately unsaturated carbon atoms, as the real ORR active sites, to strongly capture electrons from Pt.

This publication represents a kind of literary essay about the fighting against the SARS-CoV-2 coronavirus at the very beginning of the pandemic, during the first days and even hours. The personal story may help to evaluate the situation of complete uncertainty on the first days of the pandemic all of us have already forgotten now. But to remember the first moods and the first steps is a very important thing, for avoidance of new crises during possible epidemics in the future and the panic associated with them. Looking at the problem from the inside helps to understand the worries, moods and feelings of Chinese people during the current COVID-19 pandemic.

Substantial overpotentials and insufficient and unstable active sites of oxygen evolution reaction (OER) electrocatalysts limit their efficiency and stability in OER-related energy conversion and storage technologies. Here, a template editing strategy is proposed to graft highly active catalytic species onto highly conductive rigid frameworks to tackle this challenge. As a successful attempt, two types of NiO

Developing high-efficiency, inexpensive, and steady non-precious metal oxygen reduction reaction (ORR) catalysts to displace Pt-based catalysts is significant for commercial applications of Al-air battery. Here, we have prepared the Cu/Cu2O-NC catalyst with excellent ORR performance and high stability, due to the synergistic effect of Cu and Cu2O nanoparticles. The half-wave potential (0.8 V) and the limiting-current density (5.20 mA/cm2) of the Cu/Cu2O-NC are very close to those of the 20% Pt/C catalyst (0.82 V, 5.10 mA/cm2). Besides, it exhibits excellent performance with a maximal power density of 250 mW/cm2 and a stable continuous discharge for more than 90 h in the Al-air battery test. The promoting effects of Cu2O towards Cu-based ORR catalysts are illustrated as follows: (i) Cu2O is the major ORR active site by the redox of Cu(II)/Cu(I), which provides excellent ORR activities; (ii) Cu can stabilize the location of Cu2O by assisting the electron transfer to Cu(II)/Cu(I) redox, which is conducive to the high stability of the catalyst. This work provides a useful strategy for enhancing the ORR performance of Cu-based catalysts.

Metal oxides with surface protonation exhibit versatile physical and chemical properties suitable for use in many fields. Here, we develop an electrochemical route to directly protonize the physically assembled oxide particles, such as TiO2, Nb2O5, and WO3, in a Na2SO4 neutral electrolyte, which is a result of electrochemically induced oxygen vacancies reacting with water molecules. With no need of electric connection among particles or between particles and conductive substrate, the electrochemical protonation follows a bottom-up particle-by-particle surface protonation mechanism due to the fact that the protonation inducing high surface conductivity creates an efficient electron transfer pathway among particles. Our results show that electrochemical protonation of particles provides a chance to finely functionalize the surface of a single particle by only adjusting electrode potentials. Such a facile, cost-efficient, and green route is easy to run for a large-scale production and unlocks the potential of semiconductor oxides for various applications.

Public health emergencies severely affect people’s lives and health, national security, social stability, and economic development. Against the background of coronavirus disease 2019 pandemic, this study analyzes the current status of China’s public health emergency prevention and control system from the aspects of its six major systems: monitoring, early warning, and evaluation; diagnosis and treatment; basic scientific research; personnel training; material, equipment, and industry support; and social mobilization and coordinated action. We conclude that strengthening system construction is a realistic demand of China in the new development stage. China’s public health system still faces challenges regarding institutional positioning, capacity building, hardware investment, and management system. Therefore, we propose that China should establish a national overall coordination and emergency command mechanism, strengthen clinical, science, education, and industrial support capacity, and further promote international cooperation.

An industrial-scale time- and cost-effective route to produce a highly efficient and stable oxygen evolution reaction (OER) electrode is desirable and highly challenging. Here, we have developed a minute-scale Fenton-like reaction to produce a three-dimensional (3D) FeOOH/NiFe-LDH heterojunction OER electrode by using industrial Ni foam as an Ni source to react directly with a Fenton-like reagent. The resulting 3D electrode, comprising a xlow-crystalline nano-scale FeOOH/NiFe-LDH heterojunction with high electrolyte-permeability, afforded a remarkable OER performances with an overpotential of 238 mV at 100 mA cm−2, a Tafel slope of 28.9 mV dec−1, and stable running over 700 h. Our results suggested that the fully maximized three-dimensional FeOOH/NiFe-LDH heterojunction interactions would be the origination of the high OER activity, exhibiting big prospects for industrial-scale applications.

An efficient and low-cost oxygen evolution reaction (OER) electrocatalyst is key for electrochemical energy conversion and storage technologies. However, there is a lack of a strategy to guide the development of cost-effective antiperovskite nitrides with composition-sensitive function adjustability. Herein, we triggered the low-spin to high-spin transition of Fe3+ in Cu0.5NFe3.5 by partially doping Ni at the Fe sites, enabling Cu0.5NFe3Ni0.5 to significantly accelerate the oxidation of the in situ electrochemically formed amorphous FeNi (oxy)hydroxide redox couple, an initial water oxidation step, as well as subsequent water oxidation. Theoretical calculations indicated that the high-spin Fe3+ induces the formation of a paramagnetic FeNi (oxy)hydroxide catalytic layer on the ferromagnetic Cu0.5NFe3Ni0.5 core to accelerate the OER kinetics, thus Cu0.5NFe3Ni0.5 displays an overpotential of 244 mV at 10 mA cm−2 as an outstanding OER electrocatalyst, outperforming the benchmark IrO2 catalyst. Our findings are expected to unlock the potential of designing ideal antiperovskite-based electrocatalysts with adjustable spin states for use in the energy conversion and storage fields.

The photoelectrochemical (PEC) water splitting determines by the light absorption and charge extraction/injection. Here, we dispersedly modified the core-shell structured Ni@Niy Fe1-y (OH)2 on Si photoanodes and in-situ electrochemically converted it to Ni@Niy Fe1-y OOH to form a Si/SiOx /Ni@Niy Fe1-y OOH assembly, exhibiting the adjustable band bending and catalytic ability in water oxidation depending closely on the composition of Niy Fe1-y OOH. Combining with the island-like dispersed distribution to maximize the light absorption and the Ni@Niy Fe1-y shell as a high work function and a catalytic layer to simultaneously enlarge charge extraction and injection, the Si/SiOx /Ni@Ni0.7 Fe0.3 OOH assembly achieved an onset potential of 1.0 VRHE , a saturated current density of 35.4 mA cm-2 and a more than 50 h stability in an electrolyte with pH 9 under AM1.5G simulated sunlight irradiation. Our findings suggested that regulating the charge energetics at Si-electrolyte interface by discontinuously modifying a composition-adjustable core-shell structure is a potential route to develop highly efficient PEC devices.

For heterojunction semiconductor photoelectrodes, efficient charge separation is localized in the junction-induced electric field region and charge transfer follows a band-to-band charge-transfer pathway. Here, we found that polaron states at the heterojunction interface have a function of storing and transferring electrons. As a successful demonstration, we verified that the polaron states (Ti3+OH) on TiO2 are not passivated when used to create a CdS/TiO2 heterojunction and function as an efficient pathway for massively capturing, storing, and transferring the electrons from conduction bands of both TiO2 and CdS, thus effectively enhancing the charge separation efficiency of the heterojunction photoanode. The electron throughput of polaron states remains a positive correlation with polaron state density. Interfacial electron transfer through the TiO2 surface polaron states has great potential application in the development of high-performance heterojunction devices based on TiO2.

The oxygen evolution reaction (OER) is a vital proton donor for various clean energy technologies. Here, we synthesized IrOx-decorated ultrathin NiFe-LDH nanosheets (thickness 1–2 nm) by a one-step co-precipitation method. The IrOx was uniformly dispersed on the surface of ultrathin NiFe-LDH nanosheets, greatly increasing the active sites and the electric conductivity for NiFe-LDH. As a result, the IrOx/U-NiFe-LDH exhibited excellent OER performance with a low overpotential (236 mV) and a Tafel slope (74.3 mA dec−1).

Oxidative stress caused by excess ROS often leads to cellular macromolecule damage and eventually causes various biological catastrophes. Sirt6, a member of the mammalian homolog family of yeast Sir2 NAD

High barriers of water oxidation mediated by redox couple continuously challenge to maximizing efficiency from renewables to hydrogen energy. Here, an electricity-heat complementary strategy was achieved by a heat-electricity-sensitive interconversion of the α-Ni(OH)

The redox couple oxidation as an initial step for oxygen evolution reaction (OER) may be key for high electricity consumption in electrochemical redox couple mediated water splitting. Here, we report a heat-induced magnetic transition strategy to speed up the oxidation kinetics of redox couples. The activation energy of Ni2+/Ni3+ redox couple oxidation was significantly decreased by heating the Ni0.5Fe0.5OxHy OER catalyst above Néel temperature (TN) of 70oC. In such a strategy, the heat in stead of electricity to overcome the spin flipping of Ni2+/Ni3+ oxidation through the heat-sensitive ferrimagnetic-to-paramagnetic spin state changes. The efficient heat-electricity coupling enables Ni0.5Fe0.5OxHy to produce the lowest OER overpotential of 170 mV at 100 mA cm-2 at 90 oC in alkaline electrolyte, outperforming the benchmark IrO2 catalyst. Our findings demonstrate the application potential of heat-sensitive magnetic materials in the field of electrocatalysis, which may inspire insights into designing of multi-energy complementary OER devices.

Polaron states on TiO2 photoanodes provide an important electron transfer pathway at the electrode-electrolyte interface. Here, we electrochemically doped single-crystal rutile TiO2 nanorod arrays with exposed (110) facets to produce surface polaron states, Ti3+-OH, which greatly contributed to charge separation and transfer. Our results experimentally clarified the previously confused understanding of the origin of improved photoelectrochemical (PEC) water splitting performance and verified that the enhanced PEC effects mainly arise from surface polaron states instead of grain boundary passivation.

The photoelectrochemical (PEC) water splitting determines by the light absorption and charge extraction/injection. Here, we dispersedly modified the core-shell structured Ni@Ni

Mental health literacy (MHL) is vital for raising mental health awareness, reducing stigma, and improving health-related decision making, which may have lifelong consequences for patients with mental disorders.To examine MHL about depression among rural left-behind children (LBC) in China and explore differences between LBC and non-left-behind children (NLBC).A total of 3456 rural school children (mean age = 13.02 years) in fourth to ninth grades who were living in Sichuan, Anhui, and Henan provinces were surveyed in April and July 2018 using stratified random cluster sampling.More NLBC correctly recognized depression compared with LBC (Respondents showed low levels of depression-related MHL compared with peer groups in other countries, LBC showed lower MHL than NLBC in terms of the correct recognition rate of depression, attitude toward seeking help, etc. More school-based interventions should be implemented in rural schools, and parent involvement and digital-based educational strategies should be considered.

CO2 activation is a vital knot for CO2-mediated energy conversion and storage. Frustrated Lewis pairs (FLPs) are well confirmed to be highly efficient in CO2 activation. Here, we synthesized the single-crystal ZnSn(OH)6 cube with exposed (100) facet (Sc) and ZnSn(OH)6 octahedra with exposed (111) facet (So) and created FLPs with different acid-base distance on these exposed facets by vacuum irradiation, resulting from the light unstability of terminal hydroxyls. Our results demonstrated that the FLPs with short acid-base distance on So are more efficient activation centers due to the strong orbital interactions, well exemplifying that shortening the Lewis acid-base distance is a potential route to develop highly efficient FLPs catalysts. In addition, as an initial attempt, the combination effects between facet junction separating charges and FLPs activating molecules were proposed to accelerate CO2 reduction. Our findings may provide new insights into designing photocatalysts with highly catalytic performances.

It is highly challenging to produce three-dimensional (3D) electrodes with the high activity, selectivity and durability for CO2 mediated energy conversion and storage devices. Here, we densely and uniformly dispersed Bi dendrites on 3D carbon cloth (CC) by controlling the coordinated strength between Bi ions and ligands and subsequently exposed (012) facet by reduction of chemically oxidized Bi dendrites to Bi nanoparticles (Bi NPs). As a result, the Bi NPs/CC electrode exhibited a current density of 6.8 mA cm−2 at -0.78 V vs. RHE with 97.4 % CO2-to-formate Faradaic efficiency and remarkable durability of 72 h without decay. The theoretical calculations confirmed that the exposed specific facet to stabilize the OCHO* intermediate contributed to high activity, selectivity and durability of Bi NPs/CC electrode. Our results suggested a great potential to electrochemically construct 3D electrodes for large-scale applications in CO2 conversion.

Electrochemical nitrate reduction to ammonia (NRA) catalyzed by Cu-based electrodes can realize green synthesis of NH3 while removing nitrate contaminant. However, there still lacks exploration for the effect of supporting matrixes on NRA performance of Cu-based catalysts. We present here the design of three kinds of supporting matrixes including Ni foams (NF), Cu foams (CF) and carbon clothes (CC) to electrochemically grow Cu catalysts and the investigations of their NRA performance. Results show that NF-supported Cu catalyst (Cu@NF) exhibits the best performance in terms of NH3 yield rate, selectivity and Faradaic efficiency. Remarkably, at −0.23 V vs. RHE, Cu@NF delivers a NH3 yield rate up to 0.252 mmol h−1 cm−2, outperforming Cu@CF (0.148 mmol h−1 cm−2) and Cu@CC (0.076 mmol h−1 cm−2). Moreover, Cu@NF well retains NH3 yield rate and selectivity after consecutive five cycles, demonstrating an excellent stability. It is found that NF as supporting matrix can induce Ni doping to Cu catalyst for Cu@NF, which is proposed to favor atomic hydrogen reduction pathway. This work not only explores the effect of supporting matrixes on NRA performance of Cu-based catalysts but also can be extended to design rational supporting matrixes for other electrocatalytic and electro-synthetic systems.

To break challenges in creating frustrated Lewis pairs (FLPs) on highly stable inorganic materials, an ordering FLPs route is proposed by irradiation of dual-metal hydroxide with alternating light-stable and light-unstable terminal hydroxyls on dual-metal hydroxide. As a successful example, a single-crystal ZnSn(OH)6 cube with a (100) surface of alternating Zn−OH and Sn−OH terminal hydroxyl groups is irradiated under 300 W Xe lamp to create oxygen vacancies (OVs, Lewis acid) via holes oxidizing light-unstable terminal hydroxyls at Sn sites. The FLPs are accordingly constructed between the photo-induced OVs and its proximal light-stable Zn−OH terminal hydroxyls (Lewis base), significantly contributing to the decreased barriers during capture, activation, and reduction of CO2 into CO with the assistance of H2. The present findings are a big leap for designing highly stable FLPs-based inorganic solid catalysts.

Aluminum-air (Al-air) battery has been regarded as one of the most promising next-generation energy storage devices. Manganese oxides (MnOx) are widely studied as non-noble metal oxygen reduction reaction (ORR) electrocatalysts with low cost and high stability. However, they still possess inferior ORR activity for commercial applications. In this study, an architecture of CeO2 nanoparticles decorated MnOOH nanorods (MnOOH@CeO2) is prepared by a simple one-step solvothermal method as an ORR catalyst. Interestingly, the incorporation of CeO2 can significantly strengthen the ORR activities of MnOOH. The half-wave potential of MnOOH@CeO2 reaches 0.80 V vs. RHE, which shows a 30 mV positive shift compared with MnOOH. It has been verified that the significant improvement ORR activity of MnOOH@CeO2 is attributed to their synergistic effect of MnOOH and CeO2, resulting in much better oxygen activation, oxygen enrichment, and H2O2 inhibition. In a practical double-face flow Al-air battery system, MnOOH@CeO2 catalyst even exhibits better electrocatalytic performance (the discharge voltage of 0.65 V at 400 mA cm−2, the higher energy density of 3595.4 Wh kgAl−1 and power density of 302.8 mW cm−2) than the commercial 20% Pt/C, further highlighting the multi-functions of CeO2 nanoparticles attaches to MnOOH nanorods.

China’s science and technology support system has played a significant role in fighting public health emergencies. In this study, we summarize the construction status of China’s science and technology support system for emergencies from the aspects of (1) layout of scientific research bases and platforms, (2) application of big data technology, (3) science and technology investment in public health, and (4) transformation of scientific and technological achievements. Subsequently, we analyze the challenges for the construction of the support system in China in comparison with developed countries that are advanced regarding medical science and technology. To solve the problems of weak foundation of basic medical research and lack of key core technologies, we suggest to strengthen the synergy of universities, medical institutions, and science and technology enterprises. This will improve China’s basic medical research ability and promote the research and development of original pharmaceutical products and diagnostic reagents. In view of the lack of bases and platform facilities in China, we suggest to strengthen the construction of national biological resource sample centers and build self-supported data and information sharing platforms. As for insufficient investment in public health and an imperfect personnel system, we suggest to enhance the leading role of the National Academy of Medical Sciences, increase the input of public health, and improve the personnel evaluation, reserve, and training mechanisms.

Present study was focused on a hydrometallurgical process for the separation and recovery of copper, manganese, cobalt, nickel and lithium from leaching liquor of spent lithium-ion batteries. First, copper ions were selectively extracted using Mextral®5640H as extraction reagent after the removal of impurity ions. Manganese ions were then selectively separated and precipitated using KMnO4 solution and about 99.2% manganese was removed and precipitated as MnO2 and Mn2O3. Subsequently, nickel loaded Mextral®272P was used as a new extraction reagent to separate and recover cobalt from the leaching liquor. Finally, nickel and lithium ions left in the leachate were successively precipitated using NaOH and Na3PO3 solutions. Nickel and lithium were recovered as Ni(OH)2 and Li3PO4 after filtration and drying. Recovery efficiencies could be attained as follows: 100% for copper; 99.2% for manganese, 97.8% for cobalt, 99.1% for nickel and 95.8% for lithium under their optimized experimental conditions. McCabe–Thiele extraction isotherm study was conducted for the extraction of copper and cobalt to predict the extraction stages required. It is expected that this hydrometallurgical process can be a candidate for the effective separation and comprehensive recovery of all metals from the leaching liquor.

Initiated in 2009, the Sino-American symposium on clinical and translational Medicine is now in its 5th year and has laid a strong foundation for productive partnerships. Participants now come from more than 30 U.S. academic institutions that have received U.S. National Institutes of Health (NIH)

A new SARS animal model was established by inoculating SARS coronavirus (SARS‐CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5–60 after virus inoculation. All eight animals showed a transient fever 2–3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS‐CoV‐specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS‐CoV RNA could be detected in pharyngeal swab samples using nested RT‐PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS‐CoV‐related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Environmentally hazardous substances contained in spent Li-ion batteries, such as heavy metals and nocuous organics, will pose a threat to the environment and human health. On the other hand, the sustainable recycling of spent lithium-ion batteries may bring about environmental and economic benefits. In this study, a hydrometallurgical process was adopted for the comprehensive recovery of nickel, manganese, cobalt and lithium from sulfuric acid leaching liquor from waste cathode materials of spent lithium-ion batteries. First, nickel ions were selectively precipitated and recovered using dimethylglyoxime reagent. Recycled dimethylglyoxime could be re-used as precipitant for nickel and revealed similar precipitation performance compared with fresh dimethylglyoxime. Then the separation of manganese and cobalt was conducted by solvent extraction method using cobalt loaded D2EHPA. And McCabe-Thiele isotherm was employed for the prediction of the degree of separation and the number of extraction stages needed at specific experimental conditions. Finally, cobalt and lithium were sequentially precipitated and recovered as CoC2O4 ⋅ 2H2O and Li2CO3 using ammonium oxalate solution and saturated sodium carbonate solution, respectively. Recovery efficiencies could be attained as follows: 98.7% for Ni; 97.1% for Mn, 98.2% for Co and 81.0% for Li under optimized experimental conditions. This hydrometallurgical process may promise a candidate for the effective separation and recovery of metal values from the sulfuric acid leaching liquor.

We examined the associations of common variants in ENaC genes with BP changes and hypertension incidence in a longitudinal family study. A total of 2755 Han Chinese participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) baseline examination were eligible for the current study. The average of nine BP measurements obtained using a random-zero sphygmomanometer at the baseline and each of two follow-up visits were used for the current analysis. The associations of 43 tag-SNPs in ENaC genes with BP changes and hypertension incidence were assessed using mixed models to account for the correlations of repeated measures among individuals and within families. A genotype by time interaction term was used to model differences in BP change according to genotype over time. The false discovery rate (FDR) method was used to adjust for multiple testing. During an average of 7.4 years follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and approximately 33% of participants developed hypertension. Multiple variants in ENaC genes were significantly associated with longitudinal changes in SBP after adjustment for multiple testing, including SCNN1A SNP rs11064153 ( P interaction = 5.8х10 -4 ; FDR-Q = 0.01); SCNN1G SNPs rs4299163 ( P interaction = 0.011; FDR-Q = 0.05) and rs4401050 ( P interaction = 0.001; FDR-Q = 0.01); and SCNN1B SNP rs1004749 ( P interaction = 0.006; FDR-Q = 0.03). Similar but not significant trends were observed for the associations between both rs11064153 and rs4401050 and DBP changes ( P interaction = 0.024 and 0.005, respectively; FDR-Q = 0.41 and 0.17, respectively) and between rs11604153 and hypertension incidence ( P = 0.017; FDR-Q = 0.19). Our findings indicate that ENaC genes may contribute to longitudinal BP changes in the Han Chinese population. Replication of these findings is warranted.

Piezoceramic delta wing actuators have been developed for the manipulation of the flow in the near wall region of a bounded shear flow. Velocity measurements have been obtained in a wind tunnel in the presence of steady state transitional streamwise Gortler vortices and in a fully developed turbulent boundary layer. Active piezoceramic delta wing actuators were mounted flush with the wall and were oscillated at various locations, frequencies and amplitudes. All tests were conducted at a subcritical roughness Reynolds number. The detailed actuator flow disturbance patterns have been obtained by hot-wire velocity measurements. With oscillation amplitudes of only one viscous scale, the actuator was able to delay the breakdown of the streamwise vortices. Visual studies have been conducted in a water channel. Oscillating and fixed delta wing passive actuators were operated in a steady state mode. The laser-sheet fluorescence dye visualization results show that the actuator creates spanwise streaming near the wall which produce two low speed regions further downstream. A simple model is proposed which suggests the effectiveness of the actuator increases monotonically with the frequency.

To the editor: Over the past decade, gene therapy has been successfully used to treat several monogenic disorders, and it shows promise for treating diseases of more complex etiology. In addition, the recent development of induced pluripotent stem cells now opens the possibility of transplanting genetically corrected autologous cells.1,2 Very recently, the European Medicines Agency approved the first gene therapy treatment in the Western world.3 The substantial progress over the preceding decades arguably portends the development of gene therapies for most monogenic diseases. Given this remarkable opportunity, we are proposing the creation of an International Gene Therapy Consortium for Monogenic Diseases. This consortium would facilitate coordination of the production and availability of a variety of vectors, oligonucleotides, and recombinant proteins—including zinc-finger nucleases and Tal effector nucleases—as well as support the development of suitable animal models, preclinical studies, and clinical trials. Financial resources should be developed so as to attract collaborations from the private sector to boost the development of a gene therapy industry, similar to the way the Apollo project to explore the moon stimulated growth of the space and computer industries in the 1960s. In this century, a similar concerted effort will be required to develop effective treatments and even cures of diseases here on Earth! A model for such a consortium can be found in the field of genomics. Advances in genomics have been rapid, owing in large part to the formation of international consortia such as the Human Genome and the ENCODE (Encyclopedia of DNA Elements) projects. These consortia have been awarded large budgets by various government agencies that have permitted intense collaboration among scientists as well as engagement of industry for the development of supporting technologies. The funding made available for these projects contrasts sharply with the relatively limited budgets that have been available for gene therapy research. Typically, most gene therapy researchers work as small teams on a specific disease with a relatively small budget. Moreover, the funding for gene therapy research tends to be piecemeal, with part coming from private foundations supported by patients, parents, and friends. Although these small groups can provide proof of concept for a gene therapy approach in cell and animal models, they generally lack the expertise and funding to efficiently translate their strategies to a clinical trial. The fragmentation of gene therapy research efforts and the limited funding thus present significant hurdles for clinical translation. The establishment of an international gene therapy consortium would allow these small groups to tap into broader expertise and infrastructure, increasing the likelihood of a potentially beneficial treatment moving to clinical trials. There are already smaller consortia that can serve as examples. Indeed, European Union–sponsored collaborative networks in Europe have demonstrated the advantages of consortia-fostered collaboration among basic scientists, clinical investigators, industry, patient organizations and regulatory authorities. This format of collaboration and interactive multidisciplinary networks is ideally suited to address the various challenges of this multifaceted field. Consequently, such a concerted effort is much more cost-effective. One such group, the Transatlantic Gene Therapy Consortium, has successfully developed gene therapy strategies and trials predominantly for rare hematologic and immunologic diseases. In the EU Seventh Framework Programme, two pan-European translational projects have been funded, one focusing on neuro­logical and neurodegenerative diseases (NEUROMICS), the other on rare diseases of the kidney (EuRenOmics). In the United States, the Rare Diseases Clinical Research Network was funded by the National Institutes of Health and the Office for Rare Diseases Research in order to facilitate collaboration among experts in many types of rare diseases. The FORGE Canada project, a national consortium of clinicians and scientists, is using next-generation sequencing technology to identify genes responsible for 200 rare pediatric-onset disorders and investigate their molecular etiology. The International Rare Diseases Research Consortium (IRDiRC), launched in April 2011, aims to foster international collaboration, maximizing resources and coordinating efforts in rare-diseases research. Worldwide sharing of information, data, and samples is currently hampered by the absence of an exhaustive rare-disease classification, standard terms of reference, common ontologies, and harmonized regulatory requirements. The IRDiRC has two main objectives to achieve by the year 2020: to deliver 200 new therapies for rare diseases and the means to diagnose most rare diseases. The group will next develop the scientific and policy framework to guide research activities and foster collaboration among the stakeholders to systematically explore the opportunities to accelerate the development of diagnostics and therapies for rare diseases. However, it should be emphasized that currently the majority of the 200 therapies sought by this consortium are based on the use of small molecules rather than on gene and/or cell therapy. We believe that there is a need for a larger gene therapy consortium, with a larger budget, to focus on developing definitive gene and cell therapy treatments for most monogenic hereditary diseases over the next 20 years. This consortium will permit the development of focused areas of expertise. A major impediment to the commercialization of gene therapy for rare diseases lies in the lack of a sound business model for companies owing to the small number of patients, the fact that a single treatment can cure a patient for life, and the requirements for long-term evaluation by federal agencies. As recently suggested, public funds could be used to pay for centralized manufacturing facilities and to subsidize enterprises with the necessary expertise, as has been done for vaccines.4 A worldwide consortium would also facilitate the assembly of larger cohorts of patients with specific rare diseases, which are present in very small numbers in individual countries; this would allow for more robust clinical trial designs. Finally, a gene therapy consortium could facilitate long-term evaluation of integration sites and adverse events so as to better track the safety of new therapies. The creation of an International Gene Therapy Consortium for Monogenic Diseases would thus be, for these diseases, the first concrete step toward the personalized medicine that genomic research makes possible. It should be emphasized that some of these diseases (e.g., sickle cell disease and γ-thalassemia) affect millions of peoples. Like mankind's quest to travel to the moon in the 1960s, this proposal represents a grand challenge, but we have a societal obligation to the rare-disease community to collaborate and build the infrastructure to meet it. With an international consortium in place, it is more likely that therapies will be established that help patients not only in the developed world but also in less developed parts of our planet. Importantly, current scientific developments make this a timely challenge, and, in the long term, gene therapies for these diseases should become cost-effective. Just as we witnessed with the Human Genome Project, the technologies to correct the human genome will progress over the years with the appropriate incentives, generating a boost for the new knowledge-based economy. The time to take this step is now. The scientists and directors of foundations or patient associations that would like to support the creation of such a consortium are invited to e-mail Jacques P. Tremblay at Jacques-P.Tremblay@crchul.ulaval.ca.

We report 2 cases of familial multiple endocrine neoplasia type 1 syndrome (MEN 1) in related Malaysian Chinese individuals: the son had simultaneous primary lesions in the pancreatic tail, parathyroid, adrenal gland, and hypophysis, with metastatic tumors in the left lung, mediastinum and spine; his mother had simultaneous primary lesions in the pancreatic head, parathyroid, and hypophysis, with metastatic tumors in the liver, spine, ilium, chest wall, and rib. Genetic testing of the 2 patients showed the same mutation in exon 9 of MEN1 (c.1288G>T, Glu430, encoding a stop codon). The tumors with the poorest prognosis and clinical sequelae were in the pancreas of both patients, and these were treated by percutaneous cryoablation. The number of hypoglycemic episodes in the son improved for more than 120 days, and the abdominal space occupying lesion resolved in his mother.

Notch signalling controls the differentiation of haematopoietic progenitor cells (HPCs). Here, we show that loss of membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP14), a cell surface protease expressed in bone marrow stromal cells (BMSCs), increases Notch signalling in HPCs and specifically impairs B-lymphocyte development. When co-cultured with BMSCs in vitro, HPCs differentiation towards B lymphocytes is significantly compromised on MT1-MMP-deficient BMSCs and this defect could be completely rescued by DAPT, a specific Notch signalling inhibitor. The defective B-lymphocyte development could also be largely rescued by DAPT in vivo. MT1-MMP interacts with Notch ligand Delta-like 1 (Dll1) and promotes its cleavage on cell surface in BMSCs. Ectopic MT1-MMP cleaves Dll1 and results in diminished Notch signalling in co-cultured cells. In addition, recombinant MT1-MMP cleaves a synthetic Dll1 peptide at the same site where MT1-MMP cleaves Dll1 on the cell surface. Our data suggest that MT1-MMP directly cleaves Dll1 on BMSCs to negatively regulate Notch signalling to specifically maintain normal B-cell development in bone marrow.

To examine the association between renin-angiotensin-aldosterone system (RAAS) genes and salt sensitivity of blood pressure (BP).A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was conducted among 1906 participants living in a rural region of north China where habitual sodium intake is high. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer.DBP and mean arterial pressure responses increased with the number of rs4524238 A alleles in the angiotensin II receptor type 1 gene. For example, mean DBP responses (95% confidence interval) among those with genotypes G/G, G/A, and A/A were -2.53 (-2.89 to -2.18), -3.49 (-4.13 to -2.86), and -5.78 (-9.51 to -2.06) mmHg, respectively, following the low-sodium intervention (P=0.0008). Carriers of the rare A allele of rs5479 in the hydroxysteroid (11-beta) dehydrogenase 2 gene had decreased DBP responses to low sodium (P=0.00004). Those with the C/A and C/C genotypes had DBP responses of -0.70 (-6.62 to 5.22) and -2.71 (-4.88 to -0.54) mmHg, respectively. X chromosome renin-binding protein gene markers rs1557501 and rs2269372 were associated with SBP response to low sodium in men (P=0.00004 and 0.0001, respectively). SBP responses (95% confidence interval) were -6.13 (-6.68 to -5.58) versus -4.07 (-4.88 to -3.26) and -6.04 (-6.57 to -5.52) versus -3.94 (-4.90 to -2.99) mmHg among men with major versus those with minor alleles of rs1557501 and rs2269372, respectively. Haplotype analyses of these genes supported our single-marker findings.We identified renin-angiotensin-aldosterone system variants that were predictive of salt sensitivity in a Han population with habitually high-sodium intake.