Carbonaceous minerals represent a valuable and abundant resource. Their exploitation is based on decarboxylation at elevated temperature and under oxidizing conditions, which inevitably release carbon dioxide into the atmosphere. Hydrogenation of inorganic metal carbonates opens up a new pathway for processing several metal carbonates. Preliminary experimental studies revealed significant advantages over conventional isolation technologies. Under a reducing hydrogen atmosphere, the temperature of decarboxylation is significantly lower. Carbon dioxide is not directly released into the atmosphere, but may be reduced to carbon monoxide, methane, and higher hydrocarbons, which adds value to the overall process. Apart from metal oxides in different oxidation states, metals in their elemental form may also be obtained if transition‐metal carbonates are processed under a hydrogen atmosphere. This review summarizes the most important findings and fields of the application of metal carbonate hydrogenation to elucidate the need for a detailed investigation into optimized process conditions for large‐scale applications. On earth, it is present in all three aggregate states: in gaseous form in the atmosphere (approximately 2.5×1012 tons), in the dissolved state in the hydrosphere (approximately 1016 tons), and in the solid state fixed in carbonate rocks (approximately 1014 tons).4) terrestrial carbon is fixed in carbonate rocks in the earth's crust than is actually present in the gaseous atmosphere. Carbonate rocks have been known as a valuable and abundant resource for a long time. The history of inorganic metal carbonate chemistry dates back to the early ages of solid‐state chemistry. The thermal decomposition, meaning decarboxylation reactions of metal carbonates in an oxidizing atmosphere, also known as calcination, roasting, or burning, depending on the metal species involved, represent processes that were developed first on experience, later on research, and finally on technological optimization in industrial production plants. Cato, for instance, mentioned the burning of limestone  in kilns in 184 B.C. In the 1700s, Joseph Black gave the first systematic technical explanation of the calcination of limestone, also including the evolution of gaseous carbon dioxide.3) for refractory manufacture was established over 100 years ago in Austria.3) is used for iron and steel production in areas with vast mineral iron carbonate reserves, such as AustriaCarbon dioxide CO is an ab2 and/or carbon monoxide (CO) evolve per mole of metal oxide formed. The metal oxide, in turn, gives access to retransformation into the corresponding carbonate through CO2 uptake. This characteristic provides the basis for carbon capture and storage (CCS) technologies, referred to as mineral carbonation, in which CO2 is fixed to and stored as carbonate minerals, mainly in the form of calcium and magnesium carbonate.During the decarboxylation of metal carbonates to yield the respective metal oxide (MeO), inevitably one mole of CO2 2), for example, at the Erzberg in Styria, Austria, and in China. Cobalt occurs in diverse forms in the lithosphere, often as an ore companion. Nevertheless, no major cobalt carbonate (CoCO3)‐containing ore is known. Cobalt carbonate can be produced by precipitation of water‐soluble cobalt(II)salts with alkaline‐earth carbonates. Nickel exists in diverse forms in the lithosphere, but no nickel carbonate ores are known. The industrially most important nickel carbonate is caustic nickel carbonate, 2 NiCO3⋅3 Ni(OH)2⋅4 H2O, produced by precipitation of aqueous nickel sulfate with sodium carbonate. Caustic nickel carbonate can be dehydrated to give anhydrous nickel carbonate or the hexahydrate NiCO3⋅6 H2O. Copper carbonate (CuCO3) occurs naturally as azurite 2 CuCO3⋅Cu(OH)2 (blue) and malachite CuCO3⋅Cu(OH)2 (green). Silver carbonate (Ag2(CO3)3) is not found in minerals, but precipitates from water by using soluble silver species and alkaline‐metal carbonates, such as soda. Zinc carbonate (ZnCO3) exists as smithsonite. Cadmium carbonate (CdCO3) is mostly found as an ore companion of smithsonite.Manganese is present in the lithosphere nearly as frequently as carbon or phosphorus. Manganese carbonate , methane formation is not possible through hydrogenation of alkaline‐metal carbonates , although reduction of hematite (Fe2O3) features significantly higher standard free energies of reaction.Figure 3 to yield CH4 exhibit pronounced exothermic behavior (ΔHR0<−50 kJ mol−1).Hydrogenation of the transition‐metal carbonates and MgCO4Experimental studies on the hydrogenation of metal carbonates are scarce. Although first reports date back to the late 1960s, to the best of our knowledge, there are only 20 scientific publications from six research groups. Interestingly, hardly any cross reference exists between the studies.3 externally heated “cold seal”‐type vessel, in which the carbonate charge was enclosed in a platinum foil, and left unscaled and suspended in the heated part of the vessel. Before usage, the minerals were handpicked for impurities, crushed, and heated in 30 % hydrogen. The natural mineral deposit and the composition of the minerals were not stated.Giardini and Salotti from the University of Georgia, USA, were the first to report on reactions between mineral calcite, dolomite, and siderite with pressurized hydrogen and the concomitant formation of hydrocarbons.From 1987, Reller and co‐workers from the University of Zürich, Switzerland, investigated the thermal reactivity of pure alkaline‐earth‐metal carbonates, 3d transition‐metal carbonates, and metal‐doped alkaline‐earth‐metal carbonates in pure and dilute hydrogen by thermogravimetric (TG) experiments.3 and CoCO3 without additional catalysts and a series of metal carbonates doped with catalytically active metals, and hydrogenated them in a fixed‐bed flow reactor at atmospheric pressure.−1 at a total gas flow of 9.6 cm3 min−1 and feed samples of 2 g after 0.5–1 h. To estimate the reaction rate, we calculated the hourly conversion of the respective carbonate to CH4 (CtM in % h−1), as depicted from Equation Two groups from Japan—one from the Tokyo Institute of Technology;4 formation from metal‐catalyzed CaCO3 hydrogenation, in comparison to hydrogenation of pure CaCO3.Yoshida et al. focused on CH3 and mixed‐metal/CaCO3 hydrogenation promoted with catalytically active metallic nanoparticles in a continuous‐flow, packed‐bed, stainless‐steel reactor and managed to directly convert the inorganic carbonates into C1–C3 hydrocarbons.In 2009 and 2013, Jagadeesan et al. from the Jawaharlal Nehru Centre for Advanced Scientific Research, India, investigated CaCO3, MgCO3, and CaMg(CO3)2 hydrogenation has recently become subject of detailed investigation by Baldauf‐Sommerbauer et al. from Graz University of Technology, Austria.The effect of reaction temperature, pressure, and gas atmosphere on the reaction kinetics of mineral FeCO3.A detailed list of the abovementioned studies, starting with the most recent ones, is given in Table 4.13, CaCO3, SrCO3, BaCO3, and CaMg(CO3)2 and the 3d transition‐metal carbonates MnCO3, FeCO3, CoCO3, NiCO3, and ZnCO3. Decomposition of the respective carbonates in a reducing hydrogen atmosphere occurs at lower temperatures than that of decomposition under inert or oxidizing conditions.Hydrogenation of single‐metal carbonates includes the alkaline‐earth‐metal carbonates MgCO4.1.13 and CaCO3 mineral, and synthetic SrCO3 and BaCO3 at atmospheric pressure. Equal amounts of CO2 and CO, together with H2O, were formed as gaseous products from MgCO3. In the case of CaCO3, the main volatile compound was CO (CO/CO2≈10:1) from which a change in the degradation mechanism was concluded. The concomitant formation of CO, in addition to CO2 and H2O, was dedicated to the reduction of CO2 through the reverse water‐gas shift reaction [Eq. (6)]. The amount of CO increases with increasing atomic mass of the alkaline‐earth‐metal cation due to higher decarboxylation temperatures  and the endothermic nature of the reverse water‐gas shift reaction, which shifts the equilibrium composition towards the product CO at higher temperatures. The reaction temperature for decarboxylation in hydrogen was lowered by at least 150 K compared with the analogous reaction in a nitrogen atmosphere. In a hydrogen atmosphere, all four alkaline‐earth‐metal carbonates fully degraded below temperatures of 1200 K into their respective oxides MgO, CaO, SrO, and BaO. They formed as solid conglomerates of microcrystalline domains with diameters of 10–20 nm and showed a pronounced reactivity towards the respective hydroxides and towards recarbonation.3 crystals were degraded in nitrogen and hydrogen atmospheres, distinct destruction in nitrogen occurred, which suggested that diffusion of H2 into the carbonate, where it directly reacted with fixed CO2, and reverse diffusion of formed CO and H2O proceeded faster than that of CO2 diffusion.Reller et al.O CO/CO2≈:1 from w3 were performed by Yoshida et al. in a closed circulation apparatus at a fixed H2 pressure of 0.13×105 Pa and 748 K.2 with an activation energy of 236 kJ mol−1. Initial reaction rates did not differ for varying CaCO3 amounts, which was explained by decomposition of CaCO3 and hydrogenation of released CO2 to CO. The lowest temperature at which hydrogenation occurred was 700 K. At temperatures of 700–773 K, only CO formed. Above 773 K, CO and CO2 formed. The formation of the two gaseous products differed over the course of time. Whereas CO pressure steadily increased with time, CO2 pressure abruptly reached a maximum value of 22.7 Pa and did not change subsequently.Kinetic studies with CaCO3 conversion rose with increasing reaction temperature . Under isothermal conditions, the conversion decreased with increasing pressure . In contrast to the findings of Reller et al.,4 was found in addition to CO2, CO, and H2O as gaseous products  to MgO occurred in two steps and finished at temperatures lower than 750 K. The first step corresponded to loss of water. In the second step, CO2 released from Mg5(OH)2(CO3)4 and yielded MgO as the final solid product.Hydrogenation of hydromagnesite  was not converted, but formed the main product of the product gas. Reduction of intermediate FeO was incomplete and only minor amounts of Fe were formed. In addition to the distinct difference in product composition between conversion in pure and dilute hydrogen atmospheres, solid products also differed in morphology. In pure hydrogen, the solid product contained a high amount of crystalline parts, whereas the product in dilute hydrogen featured a higher amount of fine particles. The conversion temperature significantly reduced in pure hydrogen (603 K), with respect to an inert helium atmosphere (653 K). In dilute hydrogen, decarboxylation started at 623 K.In dilute hydrogen, CH3 with partial Mg and Mn substitution, ankerite (CaaFebMgcMnd)CO3, and dolomite CaMg(CO3)2. Potassium, aluminum, and silicon existed in the form of muscovite KAl2(AlSi3O10)(OH)2, whereas a major part of the silicon was quartz (SiO2). A concentrated siderite specimen (size fraction 100–200 μm) was used for kinetic analysis in a thermobalance. During conversion under a hydrogen atmosphere, the FeCO3 content of mineral siderite was converted into elemental Fe  and only minor amounts of CO. These reactions seemed to occur simultaneously because CO2 and H2O formed concurrently. From CoCO3 conversion, barely any CH4 formed, but still significant amounts of CH4 arose from NiCO3. Consequently, Ni was confirmed to be a more efficient catalyst in a dilute hydrogen atmosphere than Co.Emmenegger performed TG experiments with synthetic CoCO3 increased from 583 K in pure hydrogen to 628 K in dilute hydrogen (5 % H2 in Ar).2 and CO2. Zinc did not show any catalytic activity for the reduction of evolved CO2. The composition of the gaseous product mixture  resembled that expected for the water‐gas equilibrium.Contrary to other 3d transition‐metal carbonates, Emmenegger found that decomposition temperatures of ZnCOy+x/2(OH)x(CO3)y⋅z H2O , combinations thereof , and mixed caustic transition‐metal/Mg carbonates (MeMg(CO3)2 with Me=Fe, Co, Ni, Cu, Zn; Me1Me2Mg(CO3)2 with Me1Me2=CuZn, Ni/Zn, Cu/Ni).− with caustic carbonates was observed. Higher water concentration shifts the equilibrium composition of potential CO2 hydrogenation to the reactant side. Consequently, all caustic metal carbonates show low catalytic hydrogenation activity compared with that of the respective neutral carbonates. Mixed transition‐metal/Mg carbonate systems show pronounced catalytic activity, which highlights the effect of the noncatalytic support material MgO. MgO forms fine particles that give access to high dispersion of the transition metals or alloys.Emmenegger investigated the hydrogenation of caustic 3d transition‐metal carbonates of the type Me4.22 evolved from the carbonate is converted into CO, CH4, or higher hydrocarbons CxHy and CxHyOz. The catalytically active transition‐metal species is formed in situ during the decomposition reaction. A wide range of transition metals  was used for doping of various main‐group metal carbonates, such as Li2CO3, Na2CO3, K2CO3, CaCO3, MgCO3, SrCO3, 4 MgCO3⋅Mg(OH)2⋅5 H2O, and BaCO3. Mixed alkaline‐earth‐metal/transition‐metal carbonates of the type MeCa(CO3)2 and Me1Me2(CO3)3 were also investigated.An admixture of transition metals to main‐group metal carbonates opens up a new pathway in metal carbonate hydrogenation: because many transition metals catalyze hydrogenation reactions, COIn general, two promising effects take place. First, the decarboxylation temperature of the alkaline and alkaline‐earth‐metal carbonates drops. Second, different gaseous compounds evolve during decomposition due to the catalytic activity of the transition‐metal species. The product composition depends on the transition metal in the carbonate.4.2.12CO3, Na2CO3, and K2CO3 at 400 K and atmospheric pressure.2 was not detected after 1 h from Li2CO3 and Na2CO3 decomposition, according to thermodynamics. Traces of CO2 were detected from K2CO3 . With all three carbonates, minor amounts of CH4 were formed .Tsuneto et al. hydrogenated nickel‐doped (2 wt %) Li4.2.22, dolomite: 14–34 MPa H2) was investigated by Giardini and Salotti.4 [Eq. 2 [Eq. 4 [Eq. (17)]. Gaseous products were CH4, C2H6, CO, CO2, and H2O. Below the dehydration temperature, Ca(OH)2 was the stable solid product.Hydrogenation of calcite and dolomite minerals at elevated temperatures  and elevated pressure 2q. 2 Eq. ; graphit4, and its higher homologues, if thermally stable under the reaction conditions, formed directly through methanation of calcite, rather than through reactions between H2, CO2, and CO. CO2 and CO were only detected at low pressure (1.4 MPa) and high reaction temperature (973 K).They assumed that CH3 and CaCO3.2 were released if Cu was used as a coprecipitate. In the case of Co, predominantly CH4 formed together with minor amounts of CO. The formation of CO2 was negligible. With Ni on MgCO3 and CaCO3, more than 90 % of the gaseous product was CH4. The formation of CxHyOz species from CaCO3 in H2 was not detected at atmospheric pressure (p=0.1 MPa). The solid products consisted of a mixture of microcrystalline alkaline‐earth‐metal oxides and elemental transition metals. Reller et al. confirmed that the formed solid products acted as effective catalysts for the partial reduction of CO2 to CO or direct conversion of CO2 into CH4. For Ni−Ca carbonate systems, the activity of the system was explained by the high dispersion of the catalytically active transition metal in the CaCO3 matrix.Reller et al. investigated the effects of Co, Ni, and Cu doping 10 %) on the hydrogenation of MgCO % on the3 in hydrogen.3, normally precipitate as caustic carbonates (hydroxocarbonates) from aqueous solutions, ions of the 4d metals Rh, Ru, and Pd precipitate as oxides or oxide hydrates and Ag predominantly forms the simple carbonate Ag2CO3. Samples from NiCO3/CaCO3 and CoCO3/CaCO3 showed that two‐phase systems formed, even at transition‐metal carbonate concentrations of 5 %, rather than replacing large amounts of Ca2+ by transition metals with similar ionic radii. TG measurements showed that thermal decomposition in hydrogen proceeded in two steps: First, decomposition and reduction of the transition‐metal carbonate below temperatures of 600–700 K with H2O evolution. Second, CaCO3 decomposition at temperatures above 600–700 K. H2O evolution might result from loss of coprecipitated water, decomposition of hydroxides to oxides  was only observed for Ni and Co. During the CaCO3 decomposition step, CO2 [Eq. 4 [Eq. The reaction in Equation (23) was observed for all transition‐metal carbonates. CO formation [Eq. (21)] did not occur in this temperature range and CH CO2 Eq. , CO . For Red3, 50 % CO and 50 % CH4 were assumed. Red4 reproduces the experimental product composition depicted in Figure 2, 27 % CH4, 24 % CO).Four case studies, Red1, Red2, Red3, and Red4, represent the extreme cases (Red1 and Red2) and mixed cases (Red3 and Red4). In Red1, full carbon conversion to CO was assumed [Eqs. 35) and (38)]. CH and (38)2 emissions and the total energy demand for all four cases are compared with the benchmark BF process in Table 2 emission reduction. The classical BF process releases 2212 kg CO2 t−1 pig iron. 100 % CO formation (Red1) saves 64 % of the CO2 emitted in the benchmark process. No CO2 is released if full conversion to CH4 is hypothesized (Red2). This scenario exhibits the highest energy demand of 5267 kW h (111 % compared to the BF process) and is not aspired to from an economic point of view. Scenarios with CO and CH4 (Red3 and Red4) show excellent CO2 emission reduction (82 and 74 %) and decreased energy demand , which underlines the high potential of the proposed concept.Total CODirect iron carbonate reduction is a high‐potential candidate to open up a new route for environmentally benign pig iron production. The findings are based on TG experiments with siderite72 emission reduction, CO2 utilization, and metal carbonate exploitation.Various aspects render metal carbonate hydrogenation a powerful means for direct and indirect CO2 reduction with the renewable energy carrier hydrogen transforms the conventional endothermic process into an overall exothermic process, which allows for significant energy savings.Under a hydrogen atmosphere, the decarboxylation temperature is significantly lower than that of the respective reaction under inert conditions. Doping with transition metals further lowers the temperature level. The combination of decarboxylation and CO2 is not  released, but reduced to CO, CH4, and higher hydrocarbons. The composition of the gaseous reaction product strongly depends on the gas atmosphere (pure or dilute hydrogen); the presence of transition‐metal species acting as in situ catalysts; and the reaction temperature, pressure, and residence time. Apart from metal oxides in various oxidation states, elemental metals are obtained as solid reaction products from transition‐metal carbonates. Tailormade products, in terms of composition and morphology, would give access to novel production routes for catalysts.In reductive metal carbonate decarboxylation, CO2 in the carbonate, others assume that hydrogen reacts with released CO2. Degradation studies in hydrogen and nitrogen revealed differences in morphology that indicate the direct reaction of H2 with CO2; however, several aspects require closer examination, especially when it comes to optimized process conditions for industrial applications. Once clarified, metal carbonate hydrogenation could provide a quantum leap in high‐emission industrial sectors, such as the iron and steel industry, if a renewable hydrogen supply is accomplished. Further potential fields of applications include the renewable production of chemicals and catalyst preparation.Until now, preliminary studies focusing on feasibility and chemism have mainly been made with metal carbonates in small‐scale apparatus, lacking transferability to industrial scale. Additionally, disagreement exists concerning the reaction mechanisms. Whereas some researchers propose the direct reaction of hydrogen with fixed COThe authors declare no conflict of interest.Susanne Lux studied technical chemistry at the Graz University of Technology in Austria. In 2009, she obtained her Ph.D. in chemical engineering under the supervision of Prof. Matthäus Siebenhofer. In 2012, she accepted a position as Assistant Professor at the Institute of Chemical Engineeering and Environmental Technology at Graz University of Technology. Her research group focuses on process intensification, with the main focus on reactive separation technologies and heterogeneous catalytic systems to address environmental challenges.Georg Baldauf‐Sommerbauer studied chemistry (B.Sc.) and chemical engineering (M.Sc./Dipl.‐Ing.) at the University of Graz and Graz University of Technology in Austria. In 2017, he successfully defended his Ph.D. thesis (supervised by M. Siebenhofer and S. Lux) on the reductive calcination of mineral carbonates. His research interest focuses on fundamental kinetic studies, as well as on applied studies towards a possible industrial implementation of renewable technologies.Matthäus Siebenhofer studied chemical engineering and received his doctoral degree in 1983 from the Graz University of Technology in Austria. Currently, he is Professor for Chemical Reaction Engineering and Head of the Institute of Chemical Engineering and Environmental Technology at Graz University of Technology.


The modified Cu2O can be directly deposited on the perovskite film as the top HTL without decomposing the perovskite to maintain an n‐i‐p structure. The efficiency (18.9%) of PSCs with surface‐modified Cu2O as the HTL is significantly higher than that (11.9%) of PSCs with unmodified Cu2O, which is also the record efficiency for a Cu2O‐based perovskite solar cell in n‐i‐p structure. The enhanced performance of PSCs is attributed to the remarkably enhanced film properties achieved through surface modification. Moreover, because of the dopant‐free technology and hydrophobic surface, the Cu2O‐based PSCs have distinctly better stability than 2,2′,7,7′‐tetrakis‐9,9′‐spiro‐bifluorene‐based PSCs.The utilization of an inorganic hole‐transport layer (HTL) is one of the most effective methods to improve the stability and reduce the cost of perovskite solar cells (PSCs). However, achieving high‐quality inorganic HTL films, especially HTL films in n‐i‐p structures, via solution processes remains a big challenge. Here, a simple surface modification strategy for low‐cost and stable cuprous oxide (Cu However, the high cost of these HTMs has severely limited the large‐scale production of PSCs. Moreover, to improve the hole mobility of organic HTMs, water‐absorbing additives such as Li‐bis(trifluoromethanesulfonyl) imide (Li‐TFSI) have been widely introduced as dopants; these additives increase the moisture absorption and decomposition of the perovskite layer.3, CuSCN, and CuI) have been successfully employed to replace organic HTMs in perovskite devices.x‐based PSCs with inverted planar structure has achieved great progress.2, ZnO, and SnO2 can be used.Perovskite solar cells (PSCs) have received significant research interest as effective photovoltaic materials due to their high solar conversion efficiencies and low cost.Spin‐coating with a nanoparticle dispersion solution is a feasible solution‐process method to deposit high‐quality films.2O) quantum dots (QDs) as an example. Cu2O, a narrow‐band‐gap semiconductor , is a promising inorganic HTM due to its low electron affinity and very high hole mobility.2O is an excellent inorganic HTM and may lead to a higher theoretical PCE than NiOx, CuSCN, CuI, and Spiro‐OMeTAD.x‐based PSCs has been achieved in p‐i‐n structure. However, this structure still suffers a competitive light absorption in the range below 550 nm from CuOx and the utilization of expensive ‐phenyl‐C61‐butyric acid methyl ester (PCBM). In this work, Cu2O QDs were synthesized in aqueous solution by a low‐temperature redox reaction.2O QDs were coated with numerous hydrophilic hydroxyls and thus hardly dispersed in nonpolar solvent, several commercial silane coupling agents were employed to modify the Cu2O surface. Notably, the functional group of the silane coupling agent has a great effect on the properties of the modified Cu2O QDs. After carefully investigating the different effects of silane coupling agents on the Cu2O QD‐based PSCs, ethenyltriethyloxysilane was found to be the best surface modification agent for Cu2O. The appropriate surface modification not only led to better dispersion of Cu2O in nonpolar solvent but also introduced a hydrophobic group on the Cu2O surface, which further formatted the moisture protection layer in PSCs. Based on this design, a compact, hydrophobic, inorganic HTM layer was fabricated, and both the efficiency and the stability of PSCs were enhanced by the presence of this layer. To verify this performance, we used Cu2O QDs as inorganic HTMs to fabricate compact TiO2/mesoporous TiO2 (mp‐TiO2)/perovskite/Cu2O/Au solar cells. As expected, the PSCs based on the Cu2O HTM exhibited excellent power conversion efficiency and high stability under long‐term illumination. Due to the high film quality of the HTM layer, a champion PCE of 18.9% was achieved by employing modified Cu2O as the HTM layer, representing an extremely high enhancement compared with that of unmodified Cu2O‐based PSCs (11.9%). Moreover, the PSCs prepared by this strategy could maintain over 90% of their initial efficiency after 30 d when stored in ambient air without encapsulation. Because this enormously enhanced performance of PSCs as a result of surface modification is universally applicable to any inorganic HTM‐based PSC, this new mechanism and approach established for PSCs could lead to a significant advance in the field toward practical PSC applications.Herein, we propose a simple surface modification approach to improve the dispersion of inorganic nanoparticles in nonpolar solvents by taking cuprous oxide . The light harvester, Cs0.05FA0.81MA0.14PbI2.55Br0.45 (denoted as CsFAMA), was then introduced using a reported one‐step deposition method, where the perovskite solution was spin‐coated on TiO2 and chlorobenzene was used as an anti‐solvent. After annealing, the Cu2O QD dispersion was introduced by the spin‐coating technique to ensure effective hole extraction and collection at the Au cathode. We plotted the energy‐level diagram of the materials used in our devices in Figure 2O QDs. It should be noted that the energy band level of Cu2O QDs before and after surface modification did not exhibit obvious difference . This result demonstrates that the amount of modification agent coated on the surface of Cu2O QDs is very small. As shown in Figure 2O QDs (−5.28 eV) in our study is similar to the VB of CsFAMA (−5.60 eV), which favors the transfer of holes from the perovskite layer into the inorganic HTM.2O QDs, the typically used nonpolar solvents cannot provide a reasonable dispersity of Cu2O QDs. Therefore, the challenge in solution processing an inorganic material onto perovskite is attaining sufficient dispersion of Cu2O QDs in a suitable solvent that does not dissolve the perovskite material. In our work, the silane coupling agent ethenyltriethyloxysilane was introduced as a surface‐modifying agent to improve the dispersion of Cu2O QDs in nonpolar solvent. The Cu2O QDs were functionalized in situ and became hydrophobic as the silane molecules reacted to form covalent bonds on the surface of the Cu2O QDs. As a result, the surface‐modified Cu2O QDs could be well dispersed in 2‐methylanisole, which led to the formation of a high‐quality film as the HTM layer . Figure 2O QDs. The size and morphology of the Cu2O particles were similar to those determined by SEM. A corresponding high‐resolution TEM image  analysis was performed. Figure S2a (Supporting Information) shows an XRD spectrum of the Cu2O QDs. The diffraction peaks are identified as pure Cu2O according to JCPDS 99‐0041 data. An intense peak at 2θ = 36.4° corresponds to the (111) crystal plane. Other prominent peaks correspond to the (200), (220), and (311) planes . As shown in Figure S2 (Supporting Information), there is no difference between the XRD patterns of unmodified and modified Cu2O, indicating that the crystalline structure of the Cu2O QDs did not change after surface modification with ethenyltriethyloxysilane. The change in surface composition was further verified by UV–vis spectroscopy . The absorption spectra of unmodified and modified Cu2O show a typical absorption onset at 560 nm. This indicates that the absorption of the Cu2O QDs did not change after ethenyltriethyloxysilane modification, which is consistent with that concluded from XRD spectra. To further study the chemical modification of ethenyltriethyloxysilane on the surface of the Cu2O QDs, the differences between the Fourier transform infrared spectroscopy (FTIR) spectra of unmodified and modified Cu2O QDs were investigated, and the result is shown in Figure S4 (Supporting Information). Both the unmodified and modified Cu2O samples contain the same band at 627 cm−1, which is attributed to the stretching vibration of Cu(I)—O (Cu2O) and agrees with previous literature. For the unmodified Cu2O QDs, the band at 3415 cm−1 corresponds to the stretching vibration of —OH groups, and the bands at 1480 and 1380 cm−1 are assigned to —OH bending vibrations. These bands prove the presence of —OH groups on the surface of the unmodified Cu2O QDs.−1 appear, indicating that the OH groups on the surface of Cu2O were replaced by silanes.2O may strongly interact with silane, as demonstrated by the band at 765 cm−1 assigned to the vibrations of Si—O—Cu.e Figure c taken fFigure2O layer on the perovskite film  of 1.00 V, a short‐circuit current density (Jsc) of 20.70 mA cm−2, and a fill factor (FF) of 57.5%, resulting in a best PCE of 11.9% in the reverse scanning direction. A device using modified Cu2O as the HTM displayed a Voc of 1.15 V, a Jsc of 22.2 mA cm−2, and an FF of 74.2%, reaching a best PCE of 18.9%. The overall efficiency enhancement mainly resulted from the significant increase in the Voc, Jsc, and FF values. Compared with the PCE (20.5%) obtained when the commonly used Spiro‐OMeTAD was employed as the HTM, the PCE of the modified Cu2O‐based device was comparable (18.9%) and was much higher than that of the unmodified Cu2O‐based device. To the best of our knowledge, the PCE of the PSC with modified Cu2O as the HTM represents the highest performance reported for a PSC with an n‐i‐p structure based on the Cu2O HTM. The device performance statistics for the devices based on unmodified Cu2O, modified Cu2O, and Spiro‐OMeTAD were obtained on the basis of 20 independent devices . The average PCE values follow the same trend as the highest values discussed above. The external quantum efficiency (EQE) spectra of the devices with different HTMs are plotted in Figure 2O, the EQE spectra of the devices employing modified Cu2O and Spiro‐OMeTAD HTM are significantly higher in the range of 300–800 nm, especially in the longer wavelength region. The increased spectral response should be attributed to the improved charge collection in the presence of HTM. The EQE of the device using Cu2O HTM is lower than that of the device using Spiro‐OMeTAD HTM in the region from 350 to 670 nm. However, the EQE of the device employing Cu2O HTM exhibits a smaller decrease in the region from 650 to 750 nm than does the device employing Spiro‐OMeTAD HTM, which can be attributed to the smaller band gap of Cu2O. Notably, the Cu2O layer can improve the EQEs of PSCs in the long wavelength region because of the photocurrent originating from the Cu2O layer, which is similar to previous reports about the extension of the photoresponse toward longer wavelengths by CuInS2 and Cu2ZnSnS4 layers.2O can potentially be used to expand the photoresponse of PSCs. As shown in Figure 2O, modified Cu2O, and Spiro‐OMeTAD are 18.9, 21.8, and 23.0 mA cm−2, respectively. The integrated current density from the EQE spectra for each device agrees with the current density obtained from the J–V curves. Furthermore, to determine the stabilized (scan‐speed‐independent) PCEs, the solar cells were probed at their maximum power point (MPP) under full‐sun illumination  was carried out to study the photogenerated charge recombination processes in PSCs. As shown in Figure 2O QDs, is drastically larger than that of perovskite/unmodified Cu2O QDs, further implying reduced recombination losses.We investigated the charge‐carrier dynamics in pristine and HTM‐containing perovskite films using steady‐state photoluminescence (SSPL) and time‐resolved PL (TRPL) spectra.2O that is stable under ambient conditions is beneficial for solar cell applications. To verify this applicability, the air stability of PSCs without encapsulation was investigated, as shown in Figure2O retained 80% of their original efficiency after 30 d, while the cells with Spiro‐OMeTAD retained only 50% after 30 d. This result indicates that such a hydroscopic ion additive (Li‐TFSL) should be avoided in practical applications because of its negative influence on device stability. Furthermore, the stability of PSCs can be further enhanced by surface modification. The modified Cu2O‐based PSC maintained over 90% of its original PCE after 30 d, exhibiting excellent ambient air stability. The difference in device stability resulted from different hydrophobicities of the HTMs. The modified Cu2O film shows a water contact angle of 88.2° , which could be comparable to that of Spiro‐based devices. In this work, we achieved the record efficiency Cu2O‐based perovskite solar cell in n‐i‐p structure by using all inorganic interfacial layer. Owing to the dopant‐free technology and hydrophobic surface of Cu2O HTM, the prepared cells show excellent long‐term durability over more than 1 month, while the performance of Spiro‐based devices quickly declined and had completely deteriorated by 30 d. This proposed new mechanism and strategy of utilizing surface modification to enhance the dispersion of inorganic HTMs in nonpolar solvents has extremely wide applicability to all available inorganic materials to achieve the best performance. Furthermore, the high PCE and remarkable stability displayed by the PSC employing all‐inorganic charge extraction layers, i.e., mesoporous TiO2 and Cu2O, make this strategy very promising for practical applications. Given the above uniqueness, this novel and as‐established approach could be universally applicable and practical for the considerable enhancement of PSCs, which may be also of significance in the field of HTM surface modification for other type solar cells and electronic devices.In summary, we have demonstrated a surface modification strategy for the dispersal of inorganic CuMaterials: Mesoporous TiO2 paste (Dyesol), formamidinium iodide (FAI), methylammonium bromide (MABr), and lead bromide (PbBr2) were purchased from Xi'an Polymer Light Technology Corp. Spiro‐OMeTAD was purchased from Lumtec Corp. Sodium hydroxide , L‐(+)‐ascorbic acid , copper(II) sulfate pentahydrate , and lead iodide  were purchased from Alfa Aesar. All of the other salts and anhydrous solvents, including Li‐TFSI salt, titanium diisopropoxide bis(acetylacetonate) , N,N‐dimethylformamide (DMF), ethanol, isopropyl alcohol, tert‐butylpyridine (tBP), chlorobenzene, acetonitrile, 1‐butanol, and dimethyl sulfoxide (DMSO), were purchased from Sigma‐Aldrich. Ethenyltriethyloxysilane, octadecyltriethoxysilane, and 3‐aminopropyltriethoxysilane were purchased from Shanghai Macklin Biochemical Co., Ltd. All of the above chemical products were used directly without further purification or treatment.2O QDsSynthesis of Cu: Deionized water (9 mL) and 100 µL of 0.1 m CuSO4 solution were added to a sample vial. The vials were kept in a water bath at 35 °C throughout the particle synthesis. Next, 350 µL of 1.0 m NaOH solution was introduced into the sample vial with vigorous stirring. Upon the addition of 500 µL of 0.2 m AA to the above solution, the solution turned bright yellow immediately. The solution was stirred for 10 min in a water bath to allow crystal growth and then centrifuged at 8500 rpm for 10 min. After the supernatant was decanted, the precipitate was centrifuged and washed three times with 40 mL of a 1:1 volume ratio of water and ethanol to remove unreacted chemicals. After a final washing with 30 mL of ethanol, the precipitate was dispersed in 2 mL of ethanol before storage and analysis.2O QDsSurface Modification of Cu: The self‐assembly monolayer of silane molecules was formed as follows: 20 mg of Cu2O QDs was diluted in 10 mL of deionized water. The silane coupling agent was added in different molar ratios  to determine the optimal concentration. The mixed solution was stirred for 120 min to allow the alkylalkoxysilane molecules to self‐assemble on the Cu2O surface. Subsequently, the Cu2O QDs were washed with ethanol three times to remove the physically absorbed silane coupling agents on the surface of the Cu2O QDs. Other silane coupling agent modifications were prepared in a similar process.Device Fabrication: Pieces of FTO glass (Nippon Sheet Glass) were cleaned with detergent, deionized water, and acetone and sonicated with ethanol in an ultrasonic bath for 30 min. Then, the FTO glass was treated in a UV cleaner for 30 min. The pieces of cleaned FTO glass were coated with 0.15 m titanium diisopropoxide bis(acetylacetonate) in 1‐butanol by the spin‐coating method at 2000 rpm for 60 s, followed by heating at 125 °C for 5 min. The resulting films were cooled to room temperature, and a 0.15 m titanium diisopropoxide bis(acetylacetonate) solution in 1‐butanol was spin‐coated on the surface again to create pin hole‐free dense TiO2 films. Then, the substrates were calcined in a box furnace at 450 °C for 30 min. An mp‐TiO2 layer was deposited on the dense TiO2 layer by spin‐coating an ethanolic TiO2 solution containing 14.3 wt% TiO2 paste at 4000 rpm for 20 s, and the film was then calcined at 500 °C for 0.5 h. To achieve higher efficiency and stability, a multiple‐component perovskite film was selected as light harvest layer as reported by the previous reference.2, 22.4 mg of MABr, and 73.4 mg of PbBr2 dissolved in 1 mL of a mixed solvent of DMF and DMSO with a volume ratio of 9:1. Then, a stock solution of 1.5 m CsI in DMSO was added to the mixed perovskite precursor to obtain the Cs0.05FA0.81MA0.14PbI2.55Br0.45 precursor solution. The perovskite films were deposited onto the TiO2 substrates via a two‐step spin‐coating procedure. The first step was performed at 1000 rpm for 10 s with an acceleration of 500 rpm s−1. The second step was performed at 4000 rpm for 35 s with a ramp‐up of 2000 rpm s−1. Chlorobenzene (≈100 µL) was quickly dropped onto the spinning substrate during the second spin‐coating step at 15 s before the end of the procedure. Afterward, the as‐prepared films were heated at 100 °C for ≈2 h until their color changed to dark red. The hole‐transport layer was prepared by spin‐coating an HTM dispersion, which was prepared by dispersing Cu2O QDs in 2‐methylanisole (20 mg mL−1), at 4000 rpm for 30 s. The Spiro‐OMeTAD solution was prepared by dissolving Spiro‐OMeTAD at 65 mg mL−1 in a chlorobenzene solution that contained 20 µL mL−1 tBP and 70 µL mL−1 Li‐TFSI salt (170 mg mL−1 in acetonitrile). Finally, a 100 nm thick Au layer was thermally evaporated at a rate of ≈0.05 nm s−1 under a vacuum of 4 × 10−5 Torr to complete the device fabrication.Measurements and Characterization: UV–vis absorption spectra were recorded using a Perkin Elmer Lambda 950 UV–vis–NIR spectrometer. The PL spectra were acquired using a Horiba Fluoromax‐4 spectrofluorometer. The TRPL was measured with an Edinburgh Instrument FLS920 using a 375 nm laser derived from an Nd:YAG laser as the excitation source. FTIR spectral data for the devices were collected in the 700–3600 cm−1 range by using a Nicolet NEXUS 870 FT‐IR spectrometer. Drop shape analysis was performed using a drop shape analyzer (AST VCA Optima XE) with 18 MΩ water and a 4 µL dispense volume. Drops were measured at six different places across the substrate at room temperature 25 °C. XRD data were collected using a Bruker D8 Discover X‐ray diffractometer with Cu Kα radiation (1.54 Å) at 40 kV and 25 mA and with an Hi‐Star 2D area detector. TEM images were obtained using a Tecnai F30 microscope at 300 kV. The morphology and structure of the films were characterized by field emission scanning electron microscopy (ZEISS Merlin) at a 5 kV acceleration voltage. EIS data were recorded by an electrochemical workstation  in a frequency range of 1 Hz–1 MHz applied in the dark. Photocurrent density–voltage (J–V) curves were measured under AM 1.5G one‐sun illumination (100 mW cm−2) with a solar simulator (Enlitech SS‐F7‐3A) equipped with a 300 W xenon lamp and a Keithley 2400 source meter. The light intensity was adjusted by an National Renewable Energy Laboratory (NERL)‐calibrated Si solar cell. During measurement, the cell was covered with a mask possessing an aperture of 0.1 cm2. The EQE was measured with an EQE system (Enlitech QE‐R) containing a xenon lamp, monochromator, Si detector, and dual‐channel power meter.The authors declare no conflict of interest.SupplementaryClick here for additional data file.


This article has been corrected.1In the Original Investigation titled “Trends in Suicide Among Youth Aged 10 to 19 Years in the United States, 1975 to 2016,”


Mathematical modeling is often used in tissue engineering in order to overcome one of its major challenges: transformation of complex biological and rheological behaviors of cells and tissue in a mathematically predictive and physically manipulative engineering process. The successive accomplishment of this task will greatly help in quantifying and optimizing clinical application of the tissue engineering products. One of the problems emerging in this area is the relation between resting and migrating cell groups, as well as between different configurations of migrating cells and viscoelasticity. A deeper comprehension of the relation between various configurations of migrating cells and viscoelasticity at the supracellular level represents the prerequisite for optimization of the performance of the artificial epithelium. Since resting and migrating cell groups have a considerable difference in stiffness, a change in their mutual volume ratio and distribution may affect the viscoelasticity of multicellular surfaces. If those cell groups are treated as different phases, then an analogous model may be applied to represent such systems. In this work, a two-step Eyring model is developed in order to demonstrate the main mechanical and biochemical factors that influence configurations of migrating cells. This model could be also used for considering the long-time cell rearrangement under various types of applied stress. The results of this theoretical analysis point out the cause-consequence relationship between the configuration of migrating cells and rheological behavior of multicellular surfaces. Configuration of migrating cells is influenced by mechanical and biochemical perturbations, difficult to measure experimentally, which lead to uncorrelated motility. Uncorrelated motility results in (1) decrease of the volume fraction of migrating cells, (2) change of their configuration, and (3) softening of multicellular surfaces. The cell surface complex modulus for the mixed coupling mode under equilibrium conditions described by ϕPmeq, ϕPreq, ϕSmeq, and ϕSreq can be expressed from equations , /Gr∗(ω) → 1 and (2) if ϕPreq → 0 and ϕSreq → 0 while ϕPmeq + ϕSmeq = 1, then G∗(ω)/Gr∗(ω) → Gm∗(ω)/Gr∗(ω).Equation  should sϕPmeq. A higher value of ϕPmeq could be realized for higher kinetic constants k1 and k2 relative to k3 and k4. This scenario corresponds to ordered cell rearrangement with minimal effects of mechanical perturbations caused by stress accumulation and biochemical perturbations.Lange and Fabry reported that muscle cells can change their elastic modulus by over one order of magnitude from less than 10 kPa in a relaxed (resting) state to around 200 kPa in a fully activated (migrating) state caused by the accumulation of the contractile energy . The higϕreq → 0, while ϕSmeq + ϕPmeq → 1, (2) ϕreq → 1, while ϕSmeq + ϕPmeq → 0, (3) ϕSmeq≻≻ϕPmeq, (4) ϕSmeq≺≺ϕPmeq, and (5) ϕreq = ϕSmeq ≈ ϕPmeq. We presented 5 characteristic cases in Characteristic equilibrium states for cellular configurations obtained during cell surface rearrangement after uniaxial compression are estimated by equation , and theVarious 2D and 3D experimental systems will be discussed in the context of postulated characteristic cases presented as the result of our modeling considerations.The influence of uncorrelated motility to collective cell migration is estimated theoretically on two model systems: (1) cell aggregate rounding after uniaxial compression and (2) cell aggregate micropipette aspiration based on the proposed model. Both systems satisfy the following conditions: (1) cell long-time rearrangement is influenced by external stress, locally or globally, (2) it occurs via collective cell migration within the aggregate 3D surface region or its part, and (3) the rearrangement is driven by tissue surface tension and could be described by the Young-Laplace law . The modAlthough cell migration has long been studied, the manner in which the stochastic effects influence cell rearrangement within the precisely controlled process of development remains largely unknown . Stochaskm, (2) some cell groups migrate while the others (at the same time) stay in the resting state which corresponds to the median value of the relaxation rate kt, and (3) most of the cells stay in the resting state which corresponds to the relaxation rate kr ≈ 0. These three scenarios will be discussed based on the proposed model in the form of simulation.Uncorrelated motility induces changes of volume fraction and configuration of migrating cells. Consequently, it represents the main cause of change of the relaxation rate of the aggregate shape during its rounding from cycle to cycle . The avek1 is supposed to be k1 = tp−1 . The first scenario corresponds to the large volume fraction of migrating cells which could be accomplished under low or medium mechanical perturbations and low biochemical perturbations. Characteristic case 4 presented in ϕSmeq≺≺ϕPmeq, while ϕPreq ≈ ϕreq. Corresponding surface stiffness is quantified as G∗(ω)/Gr∗(ω) = ϕPmeqGm∗(ω)/Gr∗(ω). The simulation of the first scenario of cell migration is related to the volume fraction of resting cells, volume fraction of migrating cells in the form of small clusters, and volume fraction of migrating cells in the form of monolayer sheets to the following conditions k3≻≻k4, k3 ≥ k1, and k1 ≥ k2. Consequently, the proposed values of kinetic constants are k1 = 0.067min−1, k2 = 0.067min−1, k3 = 0.1min−1, and k4 = 0.01min−1. The result of simulation for the first scenario is shown in For this simulation, the rate constant n et al.  and equaϕreq = ϕSmeq ≈ ϕPmeq. The corresponding surface stiffness is quantified as G∗(ω)/Gr∗(ω) = 0.33Gm∗(ω)/Gr∗(ω). The simulation of this scenario is described by the conditions k1 ≈ k2 ≈ k3 ≈ k4 = 0.067min−1. The result of simulation for first scenario is shown in A second scenario in which some cell groups migrate while the others (at the same time) stay in the resting state corresponds to medium mechanical and biochemical perturbations. This configuration of migrating cells is more disordered than the one proposed for the first scenario. For this condition, case 5 should be the most suitable . For thiϕreq → 1. For this condition, the surface stiffness is G∗(ω)/Gr∗(ω) → 1.The third scenario corresponds to case 2  accompliN cells from the aggregate surface part is mechanically perturbed under external pressure and inserted into the pipette. This length depends on the magnitude of applied pressure. Lower pressure of 500 Pa induces activation of perturbed cells and their entrance into the pipette via collective cell migration during 120 min. However, under higher pressure, one part of perturbed cells is instantaneously inserted into the pipette. These cells undergo collective cell migration within the pipette while the other part of already perturbed cells enters into the pipette. Guevorkian et al. detected short-time contractions with the period of 3-4 minutes and long-time contractions with the period of 10-17 minutes  and (2) final regime for t ∈  [k1 ≈ k2. This assumption can be suitable for lower pressure~ 500 Pa. For higher pressures, kinetic constant k2 should be k2≺k1. Case 4 also introduces the condition that k3≻≻k4. Consequently, the values of the kinetic constants could be similar as the ones presented in k1 = 0.067min−1, k2 = 0.067min−1, k3 = 0.1min−1, k4 = 0.01min−1). The final regime corresponds to the more disordered configuration of migrating cells. This regime could be identified as case 5  mechanical and biochemical perturbations generated during collective cell migration, (2) configuration changes of migrating cells, and (3) long-time viscoelasticity of multicellular surfaces.A significant difference in cell stiffness between migrating and resting cell groups indicates that volume fraction of migrating cells and their distribution could influence long-time viscoelasticity of multicellular surfaces. This aspect of cell surface rearrangement could be treated by the analogy with physics in the form of two phase blends consisting of migrating and resting cell pseudophases. Migrating cells could form three different configurations: (1) monolayer sheets (lamellar structure), (2) small clusters, and (3) and various combinations of these two types. The lamellar structure of pseudoblends corresponds to parallel mode coupling, while the highly dispersed system in forms of small clusters points to series mode coupling. Mixed mode coupling is between them and accounts for both configuration types.We proposed the two-step Eyring model for indicating main mechanical and biochemical factors which influence configurations of migrating cells as follows: (1) accumulation of mechanical stress which leads to resting-to-migrating cell state transition and vice versa and (2) cohesiveness difference between migrating and resting pseudophases which leads to configuration changes of migrating cells from small cell clusters to monolayer sheets and vice versa. Both factors induce internal response of multicellular surfaces in the context of internal rearrangement of stress, cell signaling, and the generation of mechanical and biochemical perturbations. These perturbations are the product of uncorrelated motility. Uncorrelated motility causes a decrease of the volume fraction of migrating cells and weakening of the multicellular surface. Cell rearrangement and its impact on viscoelasticity of multicellular surfaces were elaborated on two model systems: (1) cell aggregate rounding after uniaxial compression and (2) cell aggregate micropipette aspiration under pressure. This model could be also applied for considering the long-time cell rearrangement under various types of stress.These complex phenomena provide motivation for future experiments which relate cell configurations with the rheological behavior of the multicellular surface and clarify the impact of uncorrelated motility on cell rearrangement. Experiments of the cell long-time rearrangement under stress should be combined with additional rheological experiments to characterize the surface stiffness distribution and the rate of its changes.


Based on the calculated electron band structures, the interfacial band alignments of the obtained heterostructures can be gradually tuned from type‐I (PbI2/WS2) to type‐II (PbI2/WSe2). Steady‐state photoluminescence (PL) and time‐resolved PL measurements reveal that the PL emissions from the bottom TMDC layers can be modulated from apparently enhanced (for WS2) to greatly quenched (for WSe2) compared to their monolayer counterparts, which can be attributed to the band alignment–induced distinct interfacial charge transfer behaviors. The band alignment nature of the heterostructures is further demonstrated by the PL excitation spectroscopy and interlayer exciton investigation. The realization of 2D vertical heterostructures with tunable band alignments will provide a new material platform for designing and constructing multifunctional optoelectronic devices.2D vertical van der Waals (vdW) heterostructures with atomically sharp interfaces have attracted tremendous interest in 2D photonic and optoelectronic applications. Band alignment engineering in 2D heterostructures provides a perfect platform for tailoring interfacial charge transfer behaviors, from which desired optical and optoelectronic features can be realized. Here, by developing a two‐step chemical vapor deposition strategy, direct vapor growth of monolayer PbI Energy band alignment engineering at the interface of semiconductor heterostructure is crucial for tuning its optical and electronic properties and realizing new functional photonic and optoelectronic devices.2) with a wider bandgap and higher light absorption coefficientMonolayer transition metal dichalcogenides (TMDCs) with direct bandgap covering a wide energy range are ideal candidates for preparing the 2D layered heterostructures.2 and monolayer alloying WS2(1−x)Se2x (0 ≤ x ≤ 1) through a two‐step chemical vapor deposition (CVD) strategy. By tuning different x values in the bottom alloying TMDC monolayers, the band alignment of these heterostructures emerges a transition from type‐I  to type‐II , with a transition point at x = 0.67 (PbI2/WS0.67Se1.33). Meanwhile, the photoluminescence (PL) emission from the bottom TMDC layers can also be modulated from apparently enhanced (for WS2) to greatly quenched (for WSe2) compared to their pristine monolayer counterparts, which can be attributed to the band alignment–induced distinct interfacial charge transfer behaviors. We further demonstrate the type‐I and type‐II band alignment nature of the PbI2/WS2 and PbI2/WSe2 heterostructures by photoluminescence excitation (PLE) spectroscopy and the study of interlayer exciton (I‐exciton) behaviors, respectively. These 2D layered heterostructures with engineered band alignment not only provide a platform for fundamental physical investigations but also have potential applications in integrated electronic and optoelectronic applications.Here, we demonstrate, for the first time, a direct vapor phase growth of vdW heterostructures composed of monolayer PbI2/TMDC vertical heterostructures were synthesized via a two‐step CVD strategy Se2x) monolayers were grown with the same method described in our previous works.2, WSe2, or the mixed powders was placed at the heating zone while a substrate (Si/300 nm SiO2) was placed at the downstream region of a tube furnace. The furnace was then stably heated to 1050 °C within 40 min and maintained at this temperature for 5 min, with the Ar gas flow at a rate of 50 sccm for transporting the source to the substrate. The alloying WS2(1−x)Se2x monolayers with the desired x value can be obtained by adjusting the mass ratio between the WS2 and WSe2 powders . In the second step, the substrate with as‐grown TMDC monolayers was rapidly transferred to the downstream of the other furnace with a quartz boat loaded with PbI2 powder placed at the heating zone. The furnace was then heated to 400 °C within 30 min and maintained at this temperature for 20 min with the Ar gas flow at a rate of 30 sccm. During the growth, PbI2 prefers to crystallize on the as‐grown TMDCs to form heterostructures instead of forming monolayers on the substrate, probably due to a higher absorption energy of TMDCs compared to the that with the substrate.2 can be controlled in general and the heterostructures comprising of monolayer WS2 and monolayer PbI2 were obtained. Since the PbI2 layers were grown at such a low temperature, the bottom TMDC monolayers were prevented from thermal damage during the formation of heterostructures.PbIgy Figure1a. At 2, WSe2, alloying WS2(1−x)Se2x and PbI2, the band alignments of PbI2/WS2 and PbI2/WSe2 show straddling and staggered configurations Se2x, with the x value varying from 0 to 1, both the conduction band minimum (CBM) and the valence band maximum (VBM) would become higher while the bandgap is smaller, which agrees with the previous reports.x value of the bottom WS2(1−x)Se2x monolayer and a transition point can be found with a certain x value at which the CBM of WS2(1−x)Se2x is equal to that of PbI2. This indicates that the charge transfer behaviors at the interface can be largely controlled by tuning the sign and amplitude of the band offset between the PbI2 and TMDCs in heterostructures.On the basis of ab initio simulation calculations (HSE06) of the electronic band structure of WSoying WS2−xSe2x2 monolayer on the bottom TMDCs, we took the PbI2/WS2 heterostructure as an example and recorded optical images of the heterostructures obtained with typical growth time varying from 0 to 20 min .2 and WS2 were observed, demonstrating the formation of PbI2/WS2 vertical heterostructure as well. Fast Fourier transform (FFT) of this HRTEM image  and WS2 ,2 and WS2 indicates the ultrahigh tolerance of lattice mismatch in vdW heterostructure. Additional characterization of PbI2/WS2 heterostructure is provided by cross‐sectional TEM  results of the cross section also confirm the existence of PbI2 and WS2 in the heterostructure .To reveal the growth process of the top PbIin Figure2a. The2/WS2, PbI2/WS0.67Se1.33, and PbI2/WSe2. The optical images of these heterostructures with half‐covered PbI2 are shown in Figure2, containing Eg (75.3 cm−1), A1g (95.5 cm−1), and A2u (113.1 cm−1), were observed with relative weak intensity  (417.9 cm−1) and E2g (351.9 cm−1) from WS2 and A1g(Se–W) (250.0 cm−1) from WSe2 were observed in PbI2/WS2 and PbI2/WSe2 heterostructures. The Raman spectrum of PbI2/WS0.67Se1.33 heterostructure shows additional vibrational modes of E2g(S–W) − LA(S–W) + A1g(Se–W) − LA(Se–W) (a mode) and A1g(S–W–Se) (b mode) compared to WS2 and WSe2, demonstrating the formation of alloying layer. We noted that the Raman vibrational modes of TMDCs in heterostructures all show slight blueshifts compared to the monolayer counterparts, which is probably due to the strain effect induced by the top PbI2 layer.In order to demonstrate the band alignment and the charge transfer behaviors, we choose three typical heterostructures, PbI2/WS2, PbI2/WS0.67Se1.33, and PbI2/WSe2 heterostructures is shown in Figure1–a3, respectively. Typical PL spectra collected in the heterostructures and the bare monolayers are compared in Figure 1–b3. We observed that the PL intensity of WS2 is significantly enhanced in PbI2/WS2 heterostructure compared to that in monolayer WS2. In contrast, the WSe2 PL in the PbI2/WSe2 heterostructure shows strong intensity quenching. Only a slight enhancement of the WS0.67Se1.33 PL was observed in the PbI2/WS0.67Se1.33 heterostructure. The PL enhancing or quenching of TMDCs in their corresponding heterostructures can be quantified by defining an enhancing factor of α = IH/IM, where IH and IM are the PL intensity of TMDCs in heterostructure and monolayer, respectively. The α values of ≈2.02, 1.12, and 0.09 were obtained in PbI2/WS2, PbI2/WS0.67Se1.33, and PbI2/WSe2, respectively, clearly demonstrating the transition from PL enhancement to PL quenching. In addition, we noted that the PL of the bottom monolayer all shows an obvious redshifted peak  in the heterostructure, which suggests a strong interlayer coupling between the PbI2 and bottom layers.1–c3). For both PbI2/WS2 and PbI2/WS0.67Se1.33, the PL decay curves of the TMDCs in monolayer and heterostructures are quite similar, with only a slight shift to longer time in PbI2/WS2. In contrast, the lifetime of WSe2 PL is dramatically decreased in PbI2/WSe2 heterostructure compared to the monolayer, implying an additional carrier decay channel of the WSe2 being created in the heterostructure.Steady‐state PL spectroscopy, PL mapping, and the time‐resolved photoluminescence (TRPL) spectroscopy were performed to study the PL emission intensity and dynamics of the bottom TMDC layer in these heterostructures, which can reflect the band alignment–induced interfacial charge transfer behaviors at the interface. The PL intensity mapping (at the emission wavelength of the bottom TMDCs) of PbI2/WS2 heterostructure with type‐I band alignment, upon laser excitation, both the hole and electron can transfer from the PbI2 to the WS2 layer, leading to an increased carrier population and thus enhanced WS2 PL. In addition, the transfer time between the PbI2 and WS2 layer should be at very short time scale, and these transferred carriers should recombine through the same channel of the carriers which generated in WS2 layer, resulting in the mostly unchanged PL decay curve. For PbI2/WS0.67Se1.33 heterostructure, the CBM of WS0.67Se1.33 is roughly equal to that of PbI2 monolayer, which leads to the suppression of the electron transfer from PbI2 to WS2. Therefore, we did not observe a large enhancement of the PL like in the PbI2/WS2 heterostructure. For PbI2/WSe2 heterostructure with type‐II band alignment, the photogenerated electron and hole are, respectively, separated into PbI2 and WSe2 layers after charge transfer, leading to the extra decay channel for the electrons and thereby resulting the quenching of the WSe2 PL.The observed different PL behaviors in different heterostructures can be well interpreted by the band alignment–induced charge transfer processes. For PbI2/WS2 heterostructure. The PL enhancement factor α as a function of excitation laser wavelength is shown in Figure2 as reported in the previous work.2 and WS2 layers were excited, where photogenerated carriers in PbI2 can be injected into the WS2. However, for excitation wavelength longer than 550 nm, only the WS2 layer was excited without external carrier injection so that the WS2 PL intensity in heterostructure equals to that of the monolayer WS2. The PLE experiment corroborated that the PL enhancement of WS2 originates from the charge transfer of PbI2, demonstrating the type‐I band alignment of PbI2/WS2 heterostructure. For PbI2/WSe2 heterostructure with type‐II alignment, the I‐excitons were observed and characterized. The PL spectrum collected from the PbI2/WSe2 heterostructure with a long integration time is depicted in Figure 2 and I‐exciton, respectively. The experimentally observed energy difference between the A‐exciton and I‐exciton is 52 meV, which agrees with the energy difference between the CBM of WSe2 and PbI2 obtained from theoretical calculation Se2x. These heterostructures were characterized by AFM, TEM, Raman spectroscopy, steady‐state spectroscopy, and TRPL spectroscopy. The obtained PbI2/WS2 heterostructure has the type‐I band alignment with enhanced WS2 PL emission compared to the monolayer, which agrees well with the charge transfer behavior in type‐I heterostructure. In contrast, PbI2/WSe2 heterostructure with the type‐II band alignment shows quenched WSe2 PL and much shorter PL lifetime, which is due to the band alignment–induced extra carrier decay channel and the separation of electrons and holes in different layers. In addition, interlayer excitons with much longer lifetime have also been observed in these type‐II heterostructures. We have further shown that the band alignment can be precisely tuned by introducing the WS2(1−x)Se2x alloying monolayer to prepare PbI2/WS2(1−x)Se2x heterostructures. Our work offers important guidance for preparing 2D vdW heterostructures with desirable band alignment, potentially leading to the realization of functional 2D photonic and optoelectronic devices.In summary, we have theoretically and experimentally demonstrated the band alignment engineering of direct vapor growth 2D vdW heterostructures, which consist of monolayer PbIDensity Functional Theory Calculation: Density functional (DF) theory calculations were performed using the generalized gradient approximation for the exchange‐correlation potential, the projector augmented wave method, and a plane‐wave basis set as implemented in the Vienna ab initio simulation package (VASP).2, WS2, and PbI2 monolayers while a 3 × 3 × 1 supercell was employed to model WS2xSe2(1−x) alloys. Two k‐meshes of 9 × 9 × 1 and 3 × 3 × 1 were adopted to sample the first Brillouin zones of the unit and super cells, respectively. A vacuum layer of 15 Å was used to eliminate the image interactions from adjacent unit cells along the normal layer direction. The cell shape and volume of all configurations and all atomic positions were fully relaxed until the residual force per atom was less than 0.01 eV Å−1. The band edges were aligned using the vacuum level.0.67Se1.33 and WS1.33Se0.67 alloys, as shown in Figure S3 (Supporting Information). Such an ordered substitution model substantially reduces computational costs and complicity, which was found to be able to offer good consistency with models fully considering disorders.Two ordered substitution models were used for considering the WS2/TMDC HeterostructuresCharacterizations of As‐Grown PbI: AFM measurements were in situ performed with a Bruker Dimension ICON AFM with Pt/Ir‐coated tips (ACCESS EFM). For TEM characterizations, the WS2 monolayers were first transferred onto a grid through a polymethyl methacrylate (PMMA)‐assisted positioning transfer method. Monolayers on SiO2/Si wafer were coated with PMMA  via spin‐coating at a speed of 2000 rpm for 1 min, and then maintained 2 h for baking the wafer at 180 °C. After immersing into the KOH (15 m) solution for 12 h, the PMMA film was taken out from the KOH solution and swilled fully with deionized water. The cleaned PMMA film was then removed onto a grid of copper, and this grid was exposed to acetone vapor at 40 °C in the atmosphere for the PMMA removing. Finally, the target WS2 monolayers on the grid of copper were obtained for the step‐2 growth process to form PbI2/WS2 heterostructures on grid which can be used for the TEM characterizations.Micro‐Raman Spectra and Steady‐State PL Spectra Measurements: Micro‐Raman spectra were measured using a confocal microscope  with a 532 nm diode continuous‐wave laser as the excitation. The laser beam was focused on the sample with a spot diameter of ≈800 nm from the top by an objective lens , while Raman signal was collected by the same objective lens. Steady‐state PL spectra were measured using the same confocal microscope but with 405 nm continuous‐wave laser as the excitation.TRPL Experiments: TRPL experiments were performed using a confocal microscope  as the collect device, and the emission signal was reflected into a streak camera  by Ag mirrors. A Ti:Sapphire laser pulsed at 400 nm  as the light source. The 400 nm output was generated by an 800 nm laser from a mode‐locked oscillator  after a barium metaborate (BBO) crystal. The laser beam was focused on to the sample with a spot diameter of ≈3 μm from the top by an objective lens , while PL emission was collected by the same objective lens. All the spectra were collected upon the laser excitation with a fixed pump power of 9.96 × 10−8 J pulse−1 cm−2.The authors declare no conflict of interest.SupplementaryClick here for additional data file.


PLCG1 gene, which encodes the phospholipase C γ1 isoform, is located within the commonly deleted region of the long arm of chromosome 20 (del(20q)) observed in myelodysplastic syndromes (MDS). Phospholipase C is involved in diverse physiological and pathological cellular processes through inositide signaling. We hypothesized that reduced PLCG1 expression because of haploinsufficiency by del(20q) plays a role in the molecular pathogenesis of MDS. Therefore, we analyzed PLCG1 expression in bone marrow mononuclear cells at diagnosis in 116 MDS patients with or without del(20q) by quantitative RT‐PCR to evaluate its clinical significance. The expression level of PLCG1 was significantly lower not only in MDS patients with del(20q) but also in those without del(20q) compared to that of the controls, which suggests that reduced PLCG1 expression is a common molecular event in MDS. Patients in the lowest quartile (Q4) group for PLCG1 expression had lower overall survival (OS) compared to that of other patients (Q1‐Q3)  with estimated median OS times of 22 in the Q4 group and 106 months in the Q1‐3 group. Univariate and multivariate analysis indicated reduced PLCG1 expression (Q4) was associated with lower OS , which suggests that reduced PLCG1 expression is an independent prognostic factor for OS. In addition, patients were well‐stratified for OS by combining PLCG1 expression level (Q4 vs Q1‐3) and bone marrow blast percentage (5% or more vs less than 5%). Thus, the level of PLCG1 expression at time of diagnosis is a prognostic biomarker for MDS.The  We found that reduced PLCG1 expression was associated with worse clinical outcomes, and the level of PLCG1 expression at the time of MDS diagnosis was a useful prognostic marker. Therapeutic options for MDS are limited, and no curative therapy except for allogeneic stem cell transplantation has been established. It is important to elucidate the molecular pathological mechanisms of MDS to develop curative therapies. In approximately half of MDS cases, chromosome abnormalities are found, and monosomy and chromosome deletions are frequently observed. These deleted chromosomal regions contain tumor suppressor genes that are involved in the development and progression of MDS. Decreased expression of these candidate tumor suppressor genes by haploinsufficiency because of chromosome loss may play a role in MDS molecular pathogenesis. Deletion of the long arm of chromosome 20, del(20q), is observed in approximately 5%‐10% of MDS cases.PLCG1 gene is located within the CDR of del(20q), which were determined by array comparative genomic hybridization.PLCG1 gene encodes phospholipase C γ1, which is involved in diverse physiological and pathological cellular processes by catalyzing the hydrolysis of phosphatidylinositol 4,5‐bisphosphate to generate the second messenger molecules, inositol 1,4,5‐trisphosphate and diacylglycerol.PLCB1 gene, which encodes the phospholipase C β1 isoform, another phospholipase C isoform, is often observed in MDS patients and is associated with disease progression.The 22.1Bone marrow samples taken at the time of MDS diagnosis were used for analysis. Bone marrow samples from 16 patients who were diagnosed as early‐stage malignant lymphoma without evidence of bone marrow involvement were used as controls. In addition to microscopic examination, lymphoma cell involvement in bone marrow was screened by a flow cytometric analysis and a karyotyping in control subjects. Written informed consent was obtained from all patients and control subjects. Mononuclear cells were separated from bone marrow samples and stored in liquid nitrogen until analysis. Data including patients’ demographic, disease status, medical history, clinical and laboratory findings, and outcomes were collected from medical records and a laboratory database.2.2GAPDH gene for each sample in duplicate wells. The expression level of each sample was indicated as a relative ratio to that of K562 cells to standardize different series of experiments.To analyze PLCG1 expression, quantitative RT‐PCR was performed. Total RNA was extracted from mononuclear cells and subjected to cDNA synthesis. Real‐time RT‐PCR was performed to quantify the expression level of PLCG1 by the TaqMan probe method (Applied Biosystems) using cDNA as template with co‐amplification of an endogenous control gene human GAPDH (Applied Biosystems). Expression levels of PLCG1 were obtained using the standard curve method in each experiment after normalization by the 2.3P < .05.A nonparametric Mann‐Whitney‐Wilcoxon test was used to compare PLCG1 expression levels among groups. The Kaplan‐Meier model was used to analyze the impact of PLCG1 expression on overall survival (OS); a log‐rank test was used for statistical analysis. The Cox proportional hazards model was used to evaluate clinical and biological factors associated with OS. Statistical analyses were performed using JMP Pro version 11.2 (SAS Institute Inc). A significant result was considered as a 2.4The study was conducted in accordance with the Declaration of Helsinki and reviewed by an institutional ethics committee (No. 3426).33.1A total of 116 MDS patients consisting of 69 males and 47 females with a median age of 70 years  with (n = 23) or without (n = 93) del(20q) were analyzed. Baseline patient characteristics are summarized in Table 3.2P = .0073; Figure P = .132; Figure P = .0078; Figure P = .0078; Figure First, we compared PLCG1 expression between MDS patients and control subjects. Relative PLCG1 expression was significantly reduced in 116 MDS patients compared to that of 16 control subjects (3.3P = .0053)   was 74 months Figure . By IPSSP = .0349) with a median OS time of 10 and 30 months, respectively ; the estimated median OS time in the Q4 group was 65 months, and that in the Q1‐Q3 group was not reached ; the L/Q1‐3 group had the highest survival, and the H/Q4 group had the lowest survival   was associated with poorer OS by univariate analysis as well as IPSS and IPSS‐R Table . In addi4PLCG1 gene is located within the CDR of del(20q) observed in MDS.PLCG1 gene. Recent advances in understanding the molecular genetics of MDS revealed the importance of epigenetic dysregulation of genes involved in cell growth, death, and differentiation.PLCG1 gene, involved in molecular pathogenesis of MDS.A significant reduction in PLCG1 expression was observed in MDS patients compared to that of control subjects. Previously, we found that the Reduced PLCG1 expression is associated with a lower OS in MDS patients. Univariate and multivariate analyses based on the Cox proportional hazards model revealed that reduced PLCG1 expression at the time of diagnosis is an independent prognostic biomarker for MDS. PLCG1 expression was reduced in MDS with a high blast percentage (5% or more) compared to those with a low blast percentage (less than 5%), which suggests that reduced PLCG1 has a role in the progression of MDS. Reduced PLCG1 expression may simply reflect bone marrow blast percentage, and the prognostic significance of reduced PLCG1 expression at the time of diagnosis is associated with advanced MDS. We found that reduced PLCG1 expression in subgroups divided by bone marrow blast percentage, high blast percentage (5% or more) and low blast percentage (less than 5%), was significant for prognosis. By using both factors, bone marrow percentage (5% or more) and reduced PLCG1 expression (lowest quartile), patients were well‐stratified for OS, and OS was predicted by these two factors at the time of diagnosis. It is important to determine a standardized cut‐off value for the clinical application of PLCG1 expression as a prognostic biomarker, and further investigation of PLCG1 expression in MDS patients is needed.PLCG1 gene encodes phospholipase C γ1, which has multiple roles in physiological and pathological intracellular pathways through nuclear inositide signaling and is involved in the development of human cancers including hematological malignancies.PLCB1 gene, which encodes another phospholipase C member, phospholipase C β1, is associated with leukemic transformation in MDS.PTPN1 gene, which encodes PTP‐1B, is located within the CDR of del(20q).PTPN1 gene is also a target gene that is disrupted by chromosome deletion in the molecular pathogenesis of MDS.The biological significance of reduced PLCG1 expression in MDS has not been determined. The PLCG1 expression was associated with worse clinical outcomes, and the level of PLCG1 expression at the time of MDS diagnosis was a useful prognostic marker. To understand the biological significance of reduced PLCG1 expression in MDS molecular pathogenesis, functional analysis is needed.We found that reduced


Avian influenza A (H7N9) remains circulating in China. For countries at risk of introduction of H7N9, such as Vietnam, early detection of H7N9 virus is essential for the early containment of the virus. Insulated isothermal reverse transcriptase PCR (iiRT‐PCR) is a portable PCR system that can be deployed under field conditions to identify pathogens at the sampling site. Applying PCR at the sampling site will greatly reduce the time to obtain a diagnostic result which allows the veterinary authority to take immediate action to contain disease spreading.To determine analytical and diagnostic sensitivity and specificity of the portable iiRT‐PCR for H7N9 virus detection.A panel of 59 virus isolates, including H7N9, avian influenza viruses of subtype H1 to H13, swine and human influenza viruses, Newcastle disease virus, and infectious bursal disease virus, were tested by H7 and N9 iiRT‐PCR reagents, using probes and primers specific to H7 or N9, in comparison with laboratory‐based real‐time RT‐PCR assays to determine analytical sensitivity and specificity. Fifty oropharyngeal samples from experimentally infected chicken and ducks with H7N9 and 50 non‐infected control swabs were tested by the H7 iiRT‐PCR to determine diagnostic sensitivity and specificity.The H7 and N9 iiRT‐PCR reagents yielded comparable levels of analytical sensitivity and specificity with real‐time RT‐PCR for the detection of H7N9 virus. Diagnostic sensitivity and specificity of H7 iiRT‐PCR were 98% and 100%, respectively.The observed high sensitivity and specificity of iiRT‐PCR for H7N9 detection show its potential for early detection of H7N9 in risk‐based surveillance. In Vietnam, active surveillance was conducted in live bird markets (LBMs) in 26 out of 63 provinces for H5N1 and in 14 provinces for H7N9 during 2016‐2017. From April 2017 to March 2018, the surveillance has detected influenza A virus in 38 out of 107 markets sampled (22% positive at sample level) . These markets were located in all 26 provinces. To date, H7N9 has not been detected through surveillance activities and no human infection has been reported, suggesting the virus is not currently present in Vietnam. Based on recent risk assessments, the threat of introduction of H7N9 into Vietnam remains moderate to high based on value chain studies, which have found undocumented movement of poultry into Vietnam from China and the recent occurrence of HPAI H7N9 in poultry in China.The current avian influenza surveillance in Vietnam relies on the testing of samples at regional animal health offices (RAHO's) or the National Centre for Veterinary Diagnosis (NCVD). The average time to obtain a laboratory result is 2.5 days, with the majority of this time being attributed to sample shipment and transport to the laboratories (6‐24 hours on average). Novel technologies, such as the insulated isothermal PCR (iiRT‐PCR), are portable PCR systems that can be applied under field conditions by the fast PCR reaction (in 42 minutes). The iiRT‐PCR portable system is a miniature portable device for field test, using freeze‐dried thermostable reagents and powered by rechargeable lithium batteries. The iiRT‐PCR applies the concept of Rayleigh‐Benard convection to drive a PCR reaction in capillary tubes. The primers/probe design rules are the same as for RT‐PCR. While conventional PCR requires multiple cycles of heating and cooling, iiRT‐PCR is performed through the creation of a temperature gradient in a capillary tube with a single heating source at the bottom of a capillary tube and establishment of thermal convection within the tube, mimicking the cycles of conventional real‐time PCR. This system has recently been developed to rapidly detect pathogenic viruses, including white spot syndrome virus, classical swine fever, foot and mouth disease, equine influenza, bluetongue virus, and MERS‐CoV.Taking advantage of the iiRT‐PCR portable system, the aim of this study was to validate the performance of the iiRT‐PCR portable system for H7N9 detection.22.1This study used a panel of 59 virus isolates for analytical specificity that included 28 H7N9 AIVs, 7 H7 AIVs of Eurasian lineage but not in the cluster of recent H7N9 virus in China, 15 non‐H7 AIVs, seven non‐H7 influenza viruses of swine and human origin, two poultry viruses, Newcastle disease virus, and infectious bursal disease virus  on taco™ mini Nucleic Acid Automatic Extraction System (GeneReach USA) and according to the manufacturer's instructions. The Taco mini system can be driven by AC and DC current (net or battery power), and its 5 kilograms allows users to transport it to the field Figure . The tac2.4In vitro transcribed RNA (IVT RNA) was generated from a plasmid containing a fragment of HA gene of AIV subtype H7N9 A/Anhui/1/2013 using MAXIscript T7 kit (Ambion). Residual DNA was removed using the Ambion Turbo DNA‐free kit (Life Technologies). The concentration of RNA was measured by a NanoDrop 2000 Spectrophotometer (Thermo Fisher Scientific). Serial dilutions of in vitro transcribed RNA were made in 40 ng/μL yeast tRNA to determine the limit of detection. Single use aliquots were stored at −80°C until use.2.5POCKIT™ iiRT‐PCR assay for AIV subtype H7 was performed by using POCKIT™ influenza H7 reagent set (GeneReach USA). The N9 iiRT‐PCR was developed by using the primers and probes in the RRT‐PCR for avian influenza A (H7N9) described by WHO without any modifications.Briefly, the lyophilized reagent was reconstituted with 50 μL Premix Buffer B and mixed with 5 μL nucleic acid extract. Subsequently, 50 μL of the final mixture was transferred to an R‐tube (GeneReach USA) and sealed with a cap, spun briefly, and placed into the POCKIT™ Micro Plus Nucleic Acid Analyzer (GeneReach USA). Qualitative results were generated by the built‐in algorithm and shown on the display screen within 42 minutes. Combining nucleic acid extraction (25 minutes) with Taco mini and the iiRT‐PCR procedure (42 minutes) with POCKIT Micro Plus can generate the qualitative test results in 90 minutes.2.6Taq mix. The thermocycling program was set up as follows: 50°C for 30 minutes, 95°C for 2 minutes, followed by 40 cycles of 95°C for 15 seconds, and 60°C for 45 seconds. Ct thresholds were set automatically as per manufacturers’ defaults.The M Influenza A, H7 CODA, and H7 CNIC RRT‐PCR for detection of influenza A and subtype H7 were carried out as described previously with some modifications . Primers and probes used are listed in Table 2.7Limit of detection 95% (LOD95%) of a reaction was determined by probit analysis at 95% confidence interval by SPSS v14 (SPSS). The 2 × 2 contingency tables were analyzed by kappa statistic using SPSS to determine the inter‐assay agreement.33.195% was estimated to be 11 copies/reaction of IVT RNA by probit regression analysis. The hit rates of the AIV N9 iiRT‐PCR for 300, 100, 33, 10, and 0 were 100% (5/5), 58.33% (7/12), 57.14% (4/7), 0% (0/7), and 0% (0/12), with an estimated LoD9595% of 171 copies/reaction.The analytical sensitivity of AIV H7 iiRT‐PCR was determined by using 3‐fold serial dilutions of IVT RNA. Analysis of replicates of 100, 33, 10, and 0 copies of IVT RNA showed that 100% (20/20), 100% (20/20), 90% (18/20), and 0% (0/0), respectively, of the reactions produced positive signals. The LoD−8) of representative viruses from four groups of AIV H7N9 viruses. The detection endpoint  was compared to that of RRT‐PCR assays using primers and probe set of H7 CODA and H7 CNIC. The sensitivity of AIV H7 iiRT‐PCR was shown to be comparable to that of H7 CODA RRT‐PCR assay in detecting the 4 representative H7N9 viruses, while having at least one log higher sensitivity when compared to that of H7 CNIC RRT‐PCR assay  and 24 non‐H7 viruses . Further validation is needed to show the possibility to use other sample types  or to use the system to detect different HA  or NA‐types (N6 or N8).Recently, other H7Nx were also found to be circulating in China and Southeast Asia. These H7Nx belong to the Eurasian H7‐lineage and are distinct from the Chinese H7N9. The current H7 test will most likely also detect these viruses as the H7 iiRT‐PCR primer/probe design targets a broad spectrum of H7. For public health purposes and early warning, this possible cross‐reactivity can be considered beneficial as any type of H7 is potentially zoonotic and detection of H7Nx in livestock samples can serve as an early warning system to raise public awareness of circulating animal influenza with pandemic potential. Also, the N9 protocol can detect other non‐H7N9 viruses, for example, H1N9 or H12N9 as shown in Table The innate characteristics of the iiRT‐PCR system make it a very useful tool for onsite diagnosis. The device is compact (hand‐held), uses lyophilized thermostable PCR reagents, and runs on rechargeable batteries, enabling it to be used in various field conditions  and thus reducing time of sample transportation. Having a quick result onsite will make it possible to initiate a quick response, such as initial movement control and quarantine measures in live bird markets or on farms, reducing the risks of further spread and potential human infections of H7N9. In Vietnam for example, the portable PCR was introduced into the active live bird market surveillance for the early detection of H7N9. Once a case of H7 would be detected in the field through the portable system, immediate movement restrictions will be put in place while waiting for confirmatory diagnosis from the laboratory.Results from field pilot studies (unpublished data) showed that it was feasible to install the system rapidly at any given sites and that personnel in the flied could be trained in the use of the iiRT‐PCR system within 2 days. One of the challenges of the system is how it will be incorporated into current ongoing active surveillance designs. iiRT‐PCR can be complementary to current surveillance designs, yet it needs to be clear if and how results will be confirmed by standard laboratory‐based tests  and how data sharing will occur from local levels to province or central levels.In conclusion, this study showed that field‐based portable PCR (iiRT‐PCR) can be used for the early diagnosis of H7N9 as an alternative approach to laboratory‐based real‐time PCR. Using field‐based test will reduce the time to obtain a result and will enable possible quick response measures in the field, reducing the risk of further spread and human infections with H7N9 in currently non‐infected countries.


FDH) from Desulfovibrio vulgaris Hildenborough (DvH) to metal oxides for catalytic CO2 reduction and report an in‐depth study of the resulting enzyme–material interface. Protein film voltammetry (PFV) demonstrates the stable binding of FDH on metal‐oxide electrodes and reveals the reversible and selective reduction of CO2 to formate. Quartz crystal microbalance (QCM) and attenuated total reflection infrared (ATR‐IR) spectroscopy confirm a high binding affinity for FDH to the TiO2 surface. Adsorption of FDH on dye‐sensitized TiO2 allows for visible‐light‐driven CO2 reduction to formate in the absence of a soluble redox mediator with a turnover frequency (TOF) of 11±1 s−1. The strong coupling of the enzyme to the semiconductor gives rise to a new benchmark in the selective photoreduction of aqueous CO2 to formate.The integration of enzymes with synthetic materials allows efficient electrocatalysis and production of solar fuels. Here, we couple formate dehydrogenase ( Semi‐artificial photosynthesis provides a common stage for these contrasting approaches as components from synthetic and biological origin can be combined in hybrid model systems.2 reduction to formate relies on diffusional mediators, such as methyl viologen (MV2+) and nicotinamide adenine dinucleotide (NAD+).2+ is toxic to microorganisms,+ is prohibitively expensive for fuel production.There is avid research into both biological and artificial COFDH) from Desulfovibrio vulgaris Hildenborough (DvH) as it has previously displayed robustness and high activity for the oxidation of formate in solution assays,2.FDH and porous indium‐doped tin oxide (ITO) and TiO2 electrodes in the absence of a mediator. Immobilization and loading of FDH on TiO2 were then investigated using a quartz crystal microbalance (QCM) and attenuated total reflection infrared (ATR‐IR) spectroscopy. FDH was finally coupled directly to dye‐sensitized TiO2 nanoparticles for the selective photocatalytic reduction of CO2 to formate in a diffusional mediator‐free colloidal system  and TiO2 (mesoTiO2) electrodes with a film thickness of approximately 2.5 μm .FDH (21.5 μm) was activated by incubation with the reducing agent dl‐dithiothreitol FDH‐modified electrode was placed in an electrolyte solution containing CO2/NaHCO3 and KCl at pH 6.5 under a CO2 atmosphere.The electrocatalytic activity of 2 and formate by FDH immobilized on a conductive mesoITO electrode (mesoITO|FDH). The onset potential for both CO2 reduction and formate oxidation was observed close to the thermodynamic potential (E0′=−0.36 V vs. standard hydrogen electrode (SHE), pH 6.5),FDHs from Escherichia coli and Syntrophobacter fumaroxidans on graphite electrodes.Figure FDH was immobilized on a semiconducting mesoTiO2 electrode (mesoTiO2|FDH), a similar onset potential for CO2 reduction (−0.4 V vs. SHE) was observed and the current density reached −100 μA cm−2 at −0.6 V vs. SHE  at −0.6 V vs. SHE for 2 h produced formate with a Faradaic efficiency of (92±5)% , the surface of TiO2 reached saturation after 1 h, resulting in approximately 3.5 pmol cm−2 of adsorbed FDH . After the addition of FDH to the buffer solution covering the planarTiO2  coated prism, the two characteristic amide I and amide II bands of the protein backbone structure were detected at 1650 cm−1 and 1545 cm−1, respectively.planarTiO2) or slight (in the case of mesoTiO2) changes to the band features in the amide‐band region were observed, suggesting a mainly retained backbone structure of FDH on the surface of TiO2. During the adsorption process, amide I and amide II band intensities showed an increase over time  upon increasing the ionic strength of the buffer, which agrees with the QCM experiments  to a suspension of TiO2 nanoparticles containing TEOA and a phosphonate group‐bearing dye, either a ruthenium tris‐2,2′‐bipyridine complex (RuP) or a diketopyrrolopyrrole (DPP) at pH 6.5 and 25 °C under N2 atmosphere (to protect the enzyme from aerobic damage). Both dyes are known to adsorb onto TiO2 via their phosphonate‐anchoring groups and DPP provides a precious‐metal‐free alternative to RuP.2 was introduced to the solution via the addition of NaHCO3. Upon UV‐filtered irradiation, the photoexcited dye injects electrons into the conduction band (CB) of TiO2 (ECB(TiO2)=−0.67 V vs. SHE at pH 6.5),FDH to drive CO2 reduction. The oxidized dye is regenerated by the sacrificial electron donor . A solution assay monitoring the activity of FDH by UV/Vis spectroscopy (via formate oxidation in presence of 2 mm MV2+) showed that approximately 36±7 % FDH remained active after 24 h of photocatalysis , suggesting that inactivation of FDH is likely the main reason for activity loss. The addition of MV2+ as a soluble redox mediator to RuP|TiO2|FDH showed that not all FDH present in the system is accessible to direct electron transfer across the enzyme–material interface . Control experiments demonstrated that all components are essential for formate production  and support oxidative quenching and “through‐particle” electron transfer as depicted in Figure 2 .The dye|TiOh Figure . The for−2 was calculated assuming that all FDH is adsorbed on TiO2 with a surface area of 50 m2 g−1. Saturation of the TiO2 surface with FDH in the QCM experiment was only observed when two orders of magnitude higher amounts of FDH were adsorbed  of 11±1.0 and 5±0.6 s−1 (based on CO2 conversion after 6 h) and approximately 4.9±0.2 and 2.0±0.2 μmol formate (after 24 h) were observed from CO2 using RuP and DPP‐sensitized TiO2, respectively  electron transfer across the enzyme–metal‐oxide interface is exploited for visible‐light‐driven CO2 reduction to formate. These results underline the importance of characterizing the interactions at the enzyme–material interface and future improvements in performance may arise from more controlled immobilization and more efficient electron transfer with the directly wired FDH.In summary, The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


IRE1A knockout allele. However, we found that IRE1C exerts an essential role in gametogenesis when IRE1B is also depleted. Our results identify a novel, plant‐specific IRE1 isoform and highlight that at least the control of gametogenesis in Arabidopsis requires an unexpected functional coordination of IRE1C and IRE1B. More broadly, our findings support the existence of a functional form of IRE1 that is required for development despite the remarkable absence of a protein domain that is critical for the function of other known IRE1 isoforms.The unfolded protein response (UPR), a highly conserved set of eukaryotic intracellular signaling cascades, controls the homeostasis of the endoplasmic reticulum (ER) in normal physiological growth and situations causing accumulation of potentially toxic levels of misfolded proteins in the ER, a condition known as ER stress. During evolution, eukaryotic lineages have acquired multiple UPR effectors, which have increased the pliability of cytoprotective responses to physiological and environmental stresses. The ER‐associated protein kinase and ribonuclease IRE1 is a UPR effector that is conserved from yeast to metazoans and plants. IRE1 assumes dispensable roles in growth in yeast but it is essential in mammals and plants. The Arabidopsis genome encodes two isoforms of IRE1, IRE1A and IRE1B, whose protein functional domains are conserved across eukaryotes. Here, we describe the identification of a third Arabidopsis IRE1 isoform, IRE1C. This protein lacks the ER lumenal domain that has been implicated in sensing ER stress in the IRE1 isoforms known to date. Through functional analyses, we demonstrate that IRE1C is not essential in growth and stress responses when deleted from the genome singularly or in combination with an  In response to ER stress, cells initiate the unfolded protein response (UPR), a set of integrated signaling pathways designed to restore ER homeostasis and growth. If the UPR fails, cells initiate irreversible death processes most likely to avoid the production and release of potentially harmful misfolded proteins   in yeast, metazoans, and plants . In metazoans, contrarily to the loss of Ire1β, the loss of Ire1α is lethal due to placenta failure   ) were obtained from the Arabidopsis Biological Resource Center. Seeds were sterilized with 30% (v/v) bleach and 0.1% (v/v) Triton X‐100 (Sigma) for 20 min, followed by five washes of 5 min each with sterile water. Sterilized seeds were stored at 4°C in darkness for at least 2 days to allow synchronization and plated on half‐strength Linsmaier and Skoog (LS) medium . Seedlings were grown vertically in a controlled growth chamber at 21°C under long‐day conditions (16‐hr light) with light intensity of 110 μE m−2 s−1. For quantitative real‐time polymerase chain reaction (PCR) analysis of gene expression in WT and ire1a ire1b mutant, Arabidopsis seeds were grown on half‐strength LS medium with 2% sucrose for 7 days, and root tissues were harvested for RNA extraction. For the allele transmission analyses, pollen grains from freshly dehiscent flowers from plants with the indicated genotypes in Table Arabidopsis Columbia‐0 (Col‐0) was used as wild‐type (WT) reference in this study. T‐DNA insertion lines of 2.2t test, with a p‐value < .05 considered as significant.For chronic ER stress treatment  containing the 35S::IRE1C‐YFP or ER‐ck . CFP fluorescence was monitored at excitation wavelength of 440 nm and with a bandpass of 467–502 nm emission filter, and YFP fluorescence was monitored at excitation wavelength of 514 nm and with a bandpass of 570–620 nm emission filter. Images were analyzed using ImageJ software . This isoform was also mentioned as an IRE1‐like gene in a previous work but was not characterized , have been identified  is viable and does not show obvious growth phenotypes compared with wild type (WT) . Both the length and thickness of the ire1b+/− ire1c+/- or ire1a+/− ire1b+/− ire1c+/− mutant siliques were reduced compared with WT  , and BiP3, which have been used to detect the IRE1‐regulated adaptive UPR signaling  by focusing on spliced t Figure b. For thd Figure , using Ur Figure a; DMSO. 4IRE1, Ire1p  as an ER membrane anchor. The high identity of transmembrane domain of IRE1C and IRE1A suggested to us that IRE1C could also localize at the ER. Through confocal microscopy analyses on the subcellular distribution of IRE1C, we established that IRE1C is indeed localized at the ER, as supported by co‐localization with an ER marker. The lack of accumulation of IRE1C to the apoplast, as it would be expected for a secretory protein with a N‐terminal signal peptide and no ER retention signal, argues in favor of a role of the IRE1C signal peptide as an ER targeting sequence and membrane anchor. Under this light, IRE1C assumes the topology of a type III membrane protein, similar to most members of the cytochrome P‐450 family for example  and the homozygous allele (ire1b‐ ire1c‐), which may be due to defects in meiosis; however, at what stage the segregation of the alleles may be impaired is yet unknown. The recovery of the only WT allele could be due to incomplete penetrance of IRE1C in regulation of gametogenesis or residual functions of IRE1B in the ire1b functional knockdown allele. It is yet unclear how IRE1B and IRE1C may be necessary for gametogenesis. One possibility is that in WT the kinase function of IRE1B and IRE1C may phosphorylate partially overlapping substrates. Support to this possibility is provided by the findings that the mammalian IRE1 can phosphorylate other substrates other than itself, at least in vitro , ACT2 (AT3G18780), IRE1A (AT2G17520), IRE1B (AT5G24360), IRE1C (AT3G11870), bZIP60 (AT1G42990), and BiP3 (AT1G09080).The gene accession numbers that were used in this study are as follows:  Click here for additional data file. Click here for additional data file.